Molecules

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Open AccessArticle

Chemical Composition, Antibacterial and Antifungal Activities of Crude Dittrichia viscosa (L.) Greuter Leaf Extracts

by Wafa Rhimi^1,2, Issam Ben Salem^2,*, Davide Immediato³, Mouldi Saidi², Abdennacer Boulila⁴ and Claudia Cafarchia³

¹ Faculté des Sciences de Bizerte, Université de Carthage, 7021 Zarzouna, Tunisia

² Laboratory of Biotechnology and Nuclear Technolog, National Centre of Nuclear Science and Technology (CNSTN), Sidi Thabet Technopark, 2020 Ariana, Tunisia

³ Dipartimento di Medicina Veterinaria, Università degli Studi di Bari, 70010 Valenzano, Italy

⁴ Laboratory of Natural Substances LR10INRAP02, National Institute of Research and Physico-chemical Analyses, Biotechpole of Sidi Thabet, 2020 Ariana, Tunisia

Molecules 2017, 22(7), 942; https://doi.org/10.3390/molecules22070942 - 30 Jun 2017

Cited by 36 | Viewed by 6020

Abstract

The small amount of data regarding the antifungal activity of Dittrichia viscosa (L.) Greuter against dermatophytes, Malassezia spp. and Aspergillus spp., associated with the few comparative studies on the antimicrobial activity of methanolic, ethanolic, and butanolic extracts underpins the study herein presented. The [...] Read more.

The small amount of data regarding the antifungal activity of Dittrichia viscosa (L.) Greuter against dermatophytes, Malassezia spp. and Aspergillus spp., associated with the few comparative studies on the antimicrobial activity of methanolic, ethanolic, and butanolic extracts underpins the study herein presented. The total condensed tannin (TCT), phenol (TPC), flavonoid (TFC), and caffeoylquinic acid (CQC) content of methanol, butanol, and ethanol (80% and 100%) extracts of D. viscosa were assessed and their bactericidal and fungicidal activities were evaluated. The antibacterial, anti-Candida and anti-Malassezia activities were evaluated by using the disk diffusion method, whereas the anti-Microsporum canis and anti-Aspergillus fumigatus activities were assessed by studying the toxicity effect of the extracts on vegetative growth, sporulation and germination. The methanolic extract contained the highest TPC and CQC content. It contains several phytochemicals mainly caffeoylquinic acid derivatives as determined by liquid chromatography with photodiode array and electrospray ionisation mass spectrometric detection (LC/PDA/ESI-MS) analysis. All extracts showed an excellent inhibitory effect against bacteria and Candida spp., whereas methanolic extract exhibited the highest antifungal activities against Malassezia spp., M. canis and A. fumigatus strains. The results clearly showed that all extracts, in particular the methanolic extract, might be excellent antimicrobial drugs for treating infections that are life threatening (i.e., Malassezia) or infections that require mandatory treatments (i.e., M. canis or A. fumigatus). Full article

(This article belongs to the Special Issue Special Issue Dedicated to Late Professor Takuo Okuda, “Tannins and Related Polyphenols Revisited: Chemistry, Biochemistry and Biological Activities”)

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2788 KiB

Open AccessArticle

Studies on the Two Thymine Residues in the Catalytic Core of 10-23 DNAzyme: The Impact on the Catalysis of Their 5-Substituted Functional Groups

by Pengyu Li¹, Shanshan Du¹, Yang Li¹ and Junlin He^2,*

¹ College of Life Sciences, Guizhou University, Guiyang 550025, China

² Laboratory of Bioorganic chemistry, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China

Molecules 2017, 22(7), 1011; https://doi.org/10.3390/molecules22071011 - 22 Jun 2017

Cited by 27 | Viewed by 4398

Abstract

In the 15-mer catalytic core of 10-23 DNAzyme, each residue contributes to the catalytic conformation differently. Here, the critically conserved T4 and the least conserved T8 were modified on their 5-position with hydroxyl, imidazolyl, and amino groups with a hydrogen-bonding ability. These external [...] Read more.

In the 15-mer catalytic core of 10-23 DNAzyme, each residue contributes to the catalytic conformation differently. Here, the critically conserved T4 and the least conserved T8 were modified on their 5-position with hydroxyl, imidazolyl, and amino groups with a hydrogen-bonding ability. These external functional groups induced new interactions within the catalytic core, resulting in both negative and positive effects on the catalytic activity of 10-23 DNAzyme, and the different linkages could be used to modulate the effect of the functional groups. The conservation of T4 and T8 could be recognized at the level of the nucleobase, but at the level of the functional group, T4 is not completely conserved. Their 5-methyl groups could be modified for a better performance in terms of the DNAzyme. Full article

(This article belongs to the Special Issue Nucleic Acid Chemistry and Nucleic Acid Drugs: A Themed Issue in Honor of Professor Lihe Zhang on the Occasion of His 80th Birthday)

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1598 KiB

Open AccessArticle

Synthesis and In Vitro Anti-Influenza Virus Evaluation of Novel Sialic Acid (C-5 and C-9)-Pentacyclic Triterpene Derivatives

by Xu Han^1,‡, Long-Long Si^1,‡, Yong-Ying Shi¹, Zi-Bo Fan¹, Shou-Xin Wang^1,3, Zhen-Yu Tian¹, Man Li¹, Jia-Qi Sun¹, Ping-Xuan Jiao¹, Fu-Xiang Ran¹, Yong-Min Zhang², De-Min Zhou¹ and Su-Long Xiao^1,*

¹ State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China

² Institut Parisien de Chimie Moléculaire, CNRS UMR 8232, Université Pierre & Marie Curie-Paris 6, 4 Place Jussieu, Paris 75005, France

³ School of Pharmacy, Jining Medical University, Rizhao 276826, China

^‡ These authors contributed equally to this work.

Molecules 2017, 22(7), 1018; https://doi.org/10.3390/molecules22071018 - 22 Jun 2017

Cited by 10 | Viewed by 5943

Abstract

The emergence of drug resistant variants of the influenza virus has led to a great need to identify novel and effective antiviral agents. In our previous study, a series of sialic acid (C-2 and C-4)-pentacyclic triterpene conjugates have been synthesized, and a five-fold [...] Read more.

The emergence of drug resistant variants of the influenza virus has led to a great need to identify novel and effective antiviral agents. In our previous study, a series of sialic acid (C-2 and C-4)-pentacyclic triterpene conjugates have been synthesized, and a five-fold more potent antiviral activity was observed when sialic acid was conjugated with pentacyclic triterpene via C-4 than C-2. It was here that we further reported the synthesis and anti-influenza activity of novel sialic acid (C-5 and C-9)-pentacyclic triterpene conjugates. Their structures were confirmed by ESI-HRMS, ¹H-NMR, and ¹³C-NMR spectroscopic analyses. Two conjugates (26 and 42) showed strong cytotoxicity to MDCK cells in the CellTiter-Glo assay at a concentration of 100 μM. However, they showed no significant cytotoxicity to HL-60, Hela, and A549 cell lines in MTT assay under the concentration of 10 μM (except compound 42 showed weak cytotoxicity to HL-60 cell line (10 μM, ~53%)). Compounds 20, 28, 36, and 44 displayed weak potency to influenza A/WSN/33 (H1N1) virus (100 μM, ~20–30%), and no significant anti-influenza activity was found for the other conjugates. The data suggested that both the C-5 acetylamide and C-9 hydroxy of sialic acid were important for its binding with hemagglutinin during viral entry into host cells, while C-4 and C-2 hydroxy were not critical for the binding process and could be replaced with hydrophobic moieties. The research presented herein had significant implications for the design of novel antiviral inhibitors based on a sialic acid scaffold. Full article

(This article belongs to the Special Issue Nucleic Acid Chemistry and Nucleic Acid Drugs: A Themed Issue in Honor of Professor Lihe Zhang on the Occasion of His 80th Birthday)

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Open AccessFeature PaperArticle

Albumin and Hyaluronic Acid-Coated Superparamagnetic Iron Oxide Nanoparticles Loaded with Paclitaxel for Biomedical Applications

by Elena Vismara^1,*, Chiara Bongio¹, Alessia Coletti¹, Ravit Edelman², Andrea Serafini¹, Michele Mauri³, Roberto Simonutti³

, Sabrina Bertini⁴

, Elena Urso⁴, Yehuda G. Assaraf⁵ and Yoav D. Livney^2,*

¹ Department of Chemistry, Materials and Chemical Engineering “G. Natta”, Politecnico di Milano, 20131 Milano, Italy

² Biotechnology and Food Engineering Department, Technion-Israel Institute of Technology, Haifa 3200000, Israel

³ Department of Materials Science, University of Milan Bicocca, 20125 Milano, Italy

⁴ Istituto scientifico di chimica e biochimica “G. Ronzoni”, 20133 Milano, Italy

⁵ Biology Department, Technion-Israel Institute of Technology, Haifa 3200000, Israel

Molecules 2017, 22(7), 1030; https://doi.org/10.3390/molecules22071030 - 22 Jun 2017

Cited by 57 | Viewed by 10795

Abstract

Super paramagnetic iron oxide nanoparticles (SPION) were augmented by both hyaluronic acid (HA) and bovine serum albumin (BSA), each covalently conjugated to dopamine (DA) enabling their anchoring to the SPION. HA and BSA were found to simultaneously serve as stabilizing polymers of Fe [...] Read more.

Super paramagnetic iron oxide nanoparticles (SPION) were augmented by both hyaluronic acid (HA) and bovine serum albumin (BSA), each covalently conjugated to dopamine (DA) enabling their anchoring to the SPION. HA and BSA were found to simultaneously serve as stabilizing polymers of Fe₃O₄·DA-BSA/HA in water. Fe₃O₄·DA-BSA/HA efficiently entrapped and released the hydrophobic cytotoxic drug paclitaxel (PTX). The relative amount of HA and BSA modulates not only the total solubility but also the paramagnetic relaxation properties of the preparation. The entrapping of PTX did not influence the paramagnetic relaxation properties of Fe₃O₄·DA-BSA. Thus, by tuning the surface structure and loading, we can tune the theranostic properties of the system. Full article

(This article belongs to the Special Issue Looking Forward to the Future of Heparin: New Sources, Developments and Applications)

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681 KiB

Open AccessArticle

Use of Chitosan-PVA Hydrogels with Copper Nanoparticles to Improve the Growth of Grafted Watermelon

by Homero González Gómez¹, Francisca Ramírez Godina¹, Hortensia Ortega Ortiz², Adalberto Benavides Mendoza¹

, Valentín Robledo Torres¹ and Marcelino Cabrera De la Fuente^1,*

¹ Departamento de Horticultura, Universidad Autónoma Agraria Antonio Narro, Saltillo 25315, Coahuila, Mexico

² Centro de Investigación en Química Aplicada, Blvd. Enrique Reyna Hermosillo No. 140, Saltillo 25294, Coahuila, Mexico

Molecules 2017, 22(7), 1031; https://doi.org/10.3390/molecules22071031 - 22 Jun 2017

Cited by 33 | Viewed by 6223

Abstract

Modern agriculture requires alternative practices that improve crop growth without negatively affecting the environment, as resources such as water and arable land grow scarcer while the human population continues to increase. Grafting is a cultivation technique that allows the plant to be more [...] Read more.

Modern agriculture requires alternative practices that improve crop growth without negatively affecting the environment, as resources such as water and arable land grow scarcer while the human population continues to increase. Grafting is a cultivation technique that allows the plant to be more efficient in its utilization of water and nutrients, while nanoscale material engineering provides the opportunity to use much smaller quantities of consumables compared to conventional systems but with similar or superior effects. On those grounds, we evaluated the effects of chitosan-polyvinyl alcohol hydrogel with absorbed copper nanoparticles (Cs-PVA-nCu) on leaf morphology and plant growth when applied to grafted watermelon cultivar ‘Jubilee’ plants. Stomatal density (SD), stomatal index (SI), stoma length (SL), and width (SW) were evaluated. The primary stem and root length, the stem diameter, specific leaf area, and fresh and dry weights were also recorded. Our results demonstrate that grafting induces modifications to leaf micromorphology that favorably affect plant growth, with grafted plants showing better vegetative growth in spite of their lower SD and SI values. Application of Cs-PVA-nCu was found to increase stoma width, primary stem length, and root length by 7%, 8% and 14%, respectively. These techniques modestly improve plant development and growth. Full article

(This article belongs to the Special Issue Chitin and Chitosan Derivatives: Biological Activities and Application)

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Open AccessArticle

Effect of Solution pH on the Adsorption of Paracetamol on Chemically Modified Activated Carbons

by Valentina Bernal¹

, Alessandro Erto²

, Liliana Giraldo¹ and Juan Carlos Moreno-Piraján^3,*

¹ Departamento de Química, Universidad Nacional de Colombia, Cra 30 No. 45-03, Bogotá D.C. 110231, Colombia

² Dipartimento di Ingegneria Chimica, dei Materiali e della Produzione Industriale, Università di Napoli Federico II, P. Le Tecchio 80, 80125 Napoli, Italy

³ Departamento de Química, Universidad de los Andes, Cra 1a No. 18A-10, Bogotá D.C. 110231, Colombia

Molecules 2017, 22(7), 1032; https://doi.org/10.3390/molecules22071032 - 22 Jun 2017

Cited by 160 | Viewed by 14564

Abstract

Paracetamol adsorption in acidic, neutral and basic media on three activated carbons with different chemistry surfaces was studied. A granular activated carbon (GAC) was prepared from coconut shell; starting from this sample, an oxidized activated carbon (GACo) was obtained by treating the GAC [...] Read more.

Paracetamol adsorption in acidic, neutral and basic media on three activated carbons with different chemistry surfaces was studied. A granular activated carbon (GAC) was prepared from coconut shell; starting from this sample, an oxidized activated carbon (GACo) was obtained by treating the GAC with a boiling solution of 6 M nitric acid, so to generate a greater number of oxygenated surface groups. In addition, a reduced activated carbon (GACr) was obtained by heating the GAC at 1173 K, to remove the oxygenated surface groups. Paracetamol adsorption was higher for GACr due to the lower presence of oxygenated surface functional groups. Moreover, adsorption was highest at neutral pH. The magnitude of the interactions between paracetamol molecules and activated carbons was studied by measuring the immersion enthalpies of activated carbons in solution of paracetamol at different concentrations and pH values and by calculating the interaction enthalpy. The highest value was obtained for GACr in a paracetamol solution of 1000 mg L⁻¹ at pH 7, confirming that paracetamol adsorption is favoured on basic activated carbons at pH values near to neutrality. Finally, the Gibbs energy changes confirmed the latter result, allowing explaining the different magnitudes of the interactions between paracetamol and activated carbons, as a function of solution pH. Full article

(This article belongs to the Section Green Chemistry)

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Open AccessArticle

Total Flavonoids of Drynariae Rhizoma Prevent Bone Loss Induced by Hindlimb Unloading in Rats

by Shuanghong Song^1,2, Ziyang Gao¹, Xujun Lei¹, Yinbo Niu¹, Yuan Zhang², Cuiqin Li², Yi Lu¹, Zhezhi Wang² and Peng Shang^1,*

¹ Key Laboratory for Space Bioscience and Biotechnology, Institute of Special Environmental Biophysics, School of Life Sciences, Northwestern Polytechnical University, Xi’an 710072, China

² Key Laboratory of Ministry of Education for Medicinal Resources and Natural Pharmaceutical Chemistry, National Engineering Laboratory for Resource Developing of Endangered Chinese Crude Drugs in Northwest of China, College of Life Sciences, Shaanxi Normal University, Xi’an 710062, China

Molecules 2017, 22(7), 1033; https://doi.org/10.3390/molecules22071033 - 22 Jun 2017

Cited by 42 | Viewed by 5624

Abstract

Drynariae Rhizoma is a kidney-tonifying herb that has a long history in clinical practice for the treatment of bone fractures and joint diseases in China. Flavonoids are considered to be its major active ingredients and are reported to ease bone loss in ovariectomized [...] Read more.

Drynariae Rhizoma is a kidney-tonifying herb that has a long history in clinical practice for the treatment of bone fractures and joint diseases in China. Flavonoids are considered to be its major active ingredients and are reported to ease bone loss in ovariectomized rats. However, the beneficial effects of the total flavonoids of Drynariae Rhizoma on osteoporosis caused by microgravity or mechanical inactivity remain unknown. This study assessed the effects of total Drynariae Rhizoma flavonoids (DRTF, Qihuang, Beijing, China, national medicine permit No. Z20030007, number of production: 04080081, content of DRTF ≥80%) against bone loss induced by simulated microgravity. A hindlimb unloading tail-suspended rat model was established to determine the effect of DRTF on bone mineral density (BMD), biomechanical strength and trabecular bone microarchitecture. Twenty-eight male Sprague–Dawley rats were divided into four groups: the baseline, control, hindlimb unloading with vehicle (HLU), and hindlimb unloading treated with DRTF (HLU–DRTF, 75 mg/kg/day) groups. Oral DRTF was administered for 4 weeks. The underlying mechanisms of the DRTF actions on disuse-induced osteoporosis are discussed. The results showed that DRTF treatment significantly increased the BMD and mechanical strength of tail-suspended rats. Enhanced bone turnover markers with HLU treatment were attenuated by DRTF administration. Deterioration of trabecular bone induced by HLU was prevented through elevated bone volume/tissue volume (BV/TV), trabecular number (Tb. N), trabecular thickness (Tb. Th) and decreased trabecular separation (Tb. Sp). The present study provides the first evidence that DRTF prevents bone loss induced by HLU treatment, indicating its potential application in the treatment of disuse-induced osteoporosis. Full article

(This article belongs to the Special Issue Natural Products and Chronic Diseases)

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Open AccessArticle

Herb-Drug Interaction between the Traditional Hepatoprotective Formulation and Sorafenib on Hepatotoxicity, Histopathology and Pharmacokinetics in Rats

by Chin-Tsung Ting^1,2, Yung-Yi Cheng¹

and Tung-Hu Tsai^1,3,4,5,*

¹ Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, Taipei 112, Taiwan

² Division of Gastrointestinal Surgery, Department of Surgery, Ren-Ai Branch, Taipei City Hospital, Taipei 10629, Taiwan

³ Graduate Institute of Acupuncture Science, China Medical University, Taichung 40402, Taiwan

⁴ School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 80708, Taiwan

⁵ Department of Chemical Engineering, National United University, Miaoli 36063, Taiwan

Molecules 2017, 22(7), 1034; https://doi.org/10.3390/molecules22071034 - 22 Jun 2017

Cited by 14 | Viewed by 6696

Abstract

Sorafenib has been used as a standard therapy for advanced hepatocellular carcinoma (HCC). In Asia, patients with HCC are potentially treated with the combination of sorafenib and Chinese herbal medicines to improve the efficiency and reduce the side effects of sorafenib. However, limited [...] Read more.

Sorafenib has been used as a standard therapy for advanced hepatocellular carcinoma (HCC). In Asia, patients with HCC are potentially treated with the combination of sorafenib and Chinese herbal medicines to improve the efficiency and reduce the side effects of sorafenib. However, limited information about the herb-drug interactions is available. We hypothesize that the Chinese herbal medicine may exert hepatoprotective effects on the sorafenib-treated group. The aim of this study is to investigate the pharmacokinetic mechanism of drug-drug interactions of sorafenib including interacting with hepatoprotective formulation, Long-Dan-Xie-Gan-Tang formulation (LDXGT) and with two cytochrome P450 3A4 (CYP3A4) inhibitors, grapefruit juice and ketoconazole. Liver enzyme levels and histopathology of liver slices were used to evaluate sorafenib-induced hepatotoxicity and the potential hepatoprotective effects of the LDXGT formulation on subjects treated with the combination of sorafenib and the herbal medicine. In this study, a validated HPLC-photodiode array analytical system was developed for the pharmacokinetic study of sorafenib in rats. As the result of the pharmacokinetic data, pretreatment with the LDXGT formulation did not significantly interact with sorafenib compared with sorafenib oral administration alone. Furthermore, grapefruit juice and ketoconazole did not significantly affect sorafenib metabolism. Furthermore, pretreatment with variable, single or repeat doses of the LDXGT formulation did not suppress or exacerbate the sorafenib-induced hepatotoxicity and histopathological alterations. According to these results, the LDXGT formulation is safe, but has no beneficial effects on sorafenib-induced hepatotoxicity. A detailed clinical trial should be performed to further evaluate the efficacy or adverse effects of the LDXGT formulation in combination with sorafenib in humans. Full article

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Open AccessArticle

Exogenous Feeding of Fructose and Phenylalanine Further Improves Betulin Production in Suspended Betula platyphylla Cells under Nitric Oxide Treatment

by Guizhi Fan¹, Tingting Nie¹, Jin Sheng Fan² and Yaguang Zhan^1,*

¹ College of Life Science, Northeast Forestry University, Harbin 150040, China

² College of Resources and Environmental Science, Heilongjiang University, Harbin 150040, China

Molecules 2017, 22(7), 1035; https://doi.org/10.3390/molecules22071035 - 30 Jun 2017

Cited by 7 | Viewed by 4189

Abstract

The aim of this study was to assay by NMR the metabolites which contribute to betulin production. 8-day-old suspended birch (Betula platyphylla) cells were treated by sodium nitroprusside (SNP) treatment, an NO donor, and 2-(4-carboxyphenyl)-4,4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxide (cPTIO), an NO-specific scavenger. The results [...] Read more.

The aim of this study was to assay by NMR the metabolites which contribute to betulin production. 8-day-old suspended birch (Betula platyphylla) cells were treated by sodium nitroprusside (SNP) treatment, an NO donor, and 2-(4-carboxyphenyl)-4,4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxide (cPTIO), an NO-specific scavenger. The results showed that betulin production was increased by five times after SNP treatment, similar with that of the control under cPTIO treatment. Forty one metabolites were detected after SNP treatment or cPTIO treatment. Among them, 10 were found to significantly contribute to the differences observed between controls and treated cell culture samples. To validate the contribution of the above 10 metabolites to betulin production, myo-inositol, fructose and phenylalanine based on correlation analysis between the content of 12 metabolites and betulin were used to feed birch suspension cell cultures under SNP treatment. Exogenous feeding of fructose or phenylalanine further enhanced the betulin production under SNP treatment, but myo-inositol had the opposite result. Full article

(This article belongs to the Section Metabolites)

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1471 KiB

Open AccessArticle

Molecular Structure–Affinity Relationship of Flavonoids in Lotus Leaf (Nelumbo nucifera Gaertn.) on Binding to Human Serum Albumin and Bovine Serum Albumin by Spectroscopic Method

by Xiaosheng Tang¹, Ping Tang^2,3 and Liangliang Liu^2,*

¹ Hubei Key Laboratory of Edible Wild Plants Conservation and Utilization & National Demonstration Center for Experimental Biology Education & College of Life Sciences, Hubei Key Laboratory of Pollutant Analysis & Reuse Technology, Hubei Normal University, Huangshi 435002, China

² Institute of Bast Fiber Crops, Chinese Academy of Agricultural Sciences, Changsha 410205, China

³ School of Environmental Science and Engineering, Hubei Polytechnic University, Hubei Key Laboratory of Mine Environmental Pollution Control and Remediation, Huangshi 435003, China

Molecules 2017, 22(7), 1036; https://doi.org/10.3390/molecules22071036 - 23 Jun 2017

Cited by 30 | Viewed by 5656

Abstract

Lotus leaf has gained growing popularity as an ingredient in herbal formulations due to its various activities. As main functional components of lotus leaf, the difference in structure of flavonoids affected their binding properties and activities. In this paper, the existence of 11 [...] Read more.

Lotus leaf has gained growing popularity as an ingredient in herbal formulations due to its various activities. As main functional components of lotus leaf, the difference in structure of flavonoids affected their binding properties and activities. In this paper, the existence of 11 flavonoids in lotus leaf extract was confirmed by High Performance Liquid Chromatography (HPLC) analysis and 11 flavonoids showed various contents in lotus leaf. The interactions between lotus leaf extract and two kinds of serum albumins (human serum albumin (HSA) and bovine serum albumin (BSA)) were investigated by spectroscopic methods. Based on the fluorescence quenching, the interactions between these flavonoids and serum albumins were further checked in detail. The relationship between the molecular properties of flavonoids and their affinities for serum albumins were analyzed and compared. The hydroxylation on 3 and 3’ position increased the affinities for serum albumins. Moreover, both of the methylation on 3’ position of quercetin and the C₂=C₃ double bond of apigenin and quercetin decreased the affinities for HSA and BSA. The glycosylation lowered the affinities for HSA and BSA depending on the type of sugar moiety. It revealed that the hydrogen bond force played an important role in binding flavonoids to HSA and BSA. Full article

(This article belongs to the Section Natural Products Chemistry)

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Open AccessReview

An Updated Review on Marine Anticancer Compounds: The Use of Virtual Screening for the Discovery of Small-Molecule Cancer Drugs

by Verónica Ruiz-Torres¹, Jose Antonio Encinar¹

, María Herranz-López¹

, Almudena Pérez-Sánchez¹, Vicente Galiano²

, Enrique Barrajón-Catalán^1,*

and Vicente Micol^1,3

¹ Institute of Molecular and Cell Biology (IBMC), Miguel Hernández University (UMH), Avda. Universidad s/n, Elche 03202, Spain

² Physics and Computer Architecture Department, Miguel Hernández University, Avda. Universidad s/n, Elche 03202, Spain

³ CIBER, Fisiopatología de la Obesidad y la Nutrición, CIBERobn, Instituto de Salud Carlos III., Palma de Mallorca 07122, Spain (CB12/03/30038)

Molecules 2017, 22(7), 1037; https://doi.org/10.3390/molecules22071037 - 23 Jun 2017

Cited by 162 | Viewed by 14712

Abstract

Marine secondary metabolites are a promising source of unexploited drugs that have a wide structural diversity and have shown a variety of biological activities. These compounds are produced in response to the harsh and competitive conditions that occur in the marine environment. Invertebrates [...] Read more.

Marine secondary metabolites are a promising source of unexploited drugs that have a wide structural diversity and have shown a variety of biological activities. These compounds are produced in response to the harsh and competitive conditions that occur in the marine environment. Invertebrates are considered to be among the groups with the richest biodiversity. To date, a significant number of marine natural products (MNPs) have been established as antineoplastic drugs. This review gives an overview of MNPs, both in research or clinical stages, from diverse organisms that were reported as being active or potentially active in cancer treatment in the past seventeen years (from January 2000 until April 2017) and describes their putative mechanisms of action. The structural diversity of MNPs is also highlighted and compared with the small-molecule anticancer drugs in clinical use. In addition, this review examines the use of virtual screening for MNP-based drug discovery and reveals that classical approaches for the selection of drug candidates based on ADMET (absorption, distribution, metabolism, excretion, and toxicity) filtering may miss potential anticancer lead compounds. Finally, we introduce a novel and publically accessible chemical library of MNPs for virtual screening purposes. Full article

(This article belongs to the Special Issue Metabolites of Terrestrial and Marine Origin on the Age-Related Disorders)

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Open AccessReview

CH/π Interactions in Carbohydrate Recognition

by Vojtěch Spiwok

Department of Biochemistry and Microbiology, University of Chemistry and Technology, Prague, Technická 3, Prague 6, 166 28, Czech Republic

Molecules 2017, 22(7), 1038; https://doi.org/10.3390/molecules22071038 - 23 Jun 2017

Cited by 97 | Viewed by 9356

Abstract

Many carbohydrate-binding proteins contain aromatic amino acid residues in their binding sites. These residues interact with carbohydrates in a stacking geometry via CH/π interactions. These interactions can be found in carbohydrate-binding proteins, including lectins, enzymes and carbohydrate transporters. Besides this, many non-protein aromatic [...] Read more.

Many carbohydrate-binding proteins contain aromatic amino acid residues in their binding sites. These residues interact with carbohydrates in a stacking geometry via CH/π interactions. These interactions can be found in carbohydrate-binding proteins, including lectins, enzymes and carbohydrate transporters. Besides this, many non-protein aromatic molecules (natural as well as artificial) can bind saccharides using these interactions. Recent computational and experimental studies have shown that carbohydrate–aromatic CH/π interactions are dispersion interactions, tuned by electrostatics and partially stabilized by a hydrophobic effect in solvated systems. Full article

(This article belongs to the Special Issue Protein-Carbohydrate Interactions)

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Open AccessArticle

Enhanced Antibacterial Activity of Ent-Labdane Derivatives of Salvic Acid (7α-Hydroxy-8(17)-ent-Labden-15-Oic Acid): Effect of Lipophilicity and the Hydrogen Bonding Role in Bacterial Membrane Interaction

by Javier Echeverría^1,*

, Alejandro Urzúa¹, Loreto Sanhueza² and Marcela Wilkens¹

¹ Facultad de Química y Biología, Universidad de Santiago de Chile, Casilla 40, Correo 33, Santiago 9170022, Chile

² Núcleo de Química y Bioquímica, Facultad de Ciencias, Universidad Mayor, Santiago 8580745, Chile

Molecules 2017, 22(7), 1039; https://doi.org/10.3390/molecules22071039 - 23 Jun 2017

Cited by 14 | Viewed by 5082

Abstract

In the present study, the antibacterial activity of several ent-labdane derivatives of salvic acid (7α-hydroxy-8(17)-ent-labden-15-oic acid) was evaluated in vitro against the Gram-negative bacterium Escherichia coli and the Gram-positive bacteria Staphylococcus aureus and Bacillus cereus. For all of the [...] Read more.

In the present study, the antibacterial activity of several ent-labdane derivatives of salvic acid (7α-hydroxy-8(17)-ent-labden-15-oic acid) was evaluated in vitro against the Gram-negative bacterium Escherichia coli and the Gram-positive bacteria Staphylococcus aureus and Bacillus cereus. For all of the compounds, the antibacterial activity was expressed as the minimum inhibitory concentration (MIC) in liquid media and minimum inhibitory amount (MIA) in solid media. Structure activity relationships (SAR) were employed to correlate the effect of the calculated lipophilicity parameters (logP_ow) on the inhibitory activity. Employing a phospholipidic bilayer (POPG) as a bacterial membrane model, ent-labdane-membrane interactions were simulated utilizing docking studies. The results indicate that (i) the presence of a carboxylic acid in the C-15 position, which acted as a hydrogen-bond donor (HBD), was essential for the antibacterial activity of the ent-labdanes; (ii) an increase in the length of the acylated chain at the C-7 position improved the antibacterial activity until an optimum length of five carbon atoms was reached; (iii) an increase in the length of the acylated chain by more than five carbon atoms resulted in a dramatic decrease in activity, which completely disappeared in acyl chains of more than nine carbon atoms; and (iv) the structural factors described above, including one HBD at C-15 and a hexanoyloxi moiety at C-7, had a good fit to a specific lipophilic range and antibacterial activity. The lipophilicity parameter has a predictive characteristic feature on the antibacterial activity of this class of compounds, to be considered in the design of new biologically active molecules. Full article

(This article belongs to the Special Issue Synthesis and Modification of Natural Product)

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Open AccessArticle

On the Reaction of Carbonyl Diphosphonic Acid with Hydroxylamine and O-alkylhydroxylamines: Unexpected Degradation of P-C-P Bridge

by Olga A. Khomich^1,†, Dmitry V. Yanvarev^1,†, Roman A. Novikov¹, Alexey B. Kornev¹, Elina Puljulla², Jouko Vepsäläinen², Alex R. Khomutov¹

and Sergey N. Kochetkov^1,*

¹ Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 11991 Moscow, Russia

² School of Pharmacy, Biocenter Kuopio, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio, Finland

^† These authors contributed equally to this work.

Molecules 2017, 22(7), 1040; https://doi.org/10.3390/molecules22071040 - 23 Jun 2017

Viewed by 6432

Abstract

Derivatives of methylenediphosphonic acid possess wide spectra of biological activities and are used in enzymology as research tools as well as in practical medicine. Carbonyl diphosphonic acid is a promising starting building block for synthesis of functionally substituted methylenediphosphonates. Investigation of the interaction [...] Read more.

Derivatives of methylenediphosphonic acid possess wide spectra of biological activities and are used in enzymology as research tools as well as in practical medicine. Carbonyl diphosphonic acid is a promising starting building block for synthesis of functionally substituted methylenediphosphonates. Investigation of the interaction of carbonyl diphosphonic acid with hydroxylamine clearly demonstrates that it is impossible to isolate oxime within the pH range 2–12, while only cyanophosphonic and phosphoric acids are the products of the fast proceeding Beckmann-like fragmentation. In the case of O-alkylhydroxylamines, corresponding alcohols are found in the reaction mixtures in addition to cyanophosphonic and phosphoric acids. Therefore, two residues of phosphonic acid being attached to a carbonyl group provide new properties to this carbonyl group, making its oximes very unstable. This principally differs carbonyl diphosphonic acid from structurally related phosphonoglyoxalic acid and other α-ketophosphonates. Full article

(This article belongs to the Section Organic Chemistry)

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Open AccessArticle

General Methodologies Toward cis-Fused Quinone Sesquiterpenoids. Enantiospecific Synthesis of the epi-Ilimaquinone Core Featuring Sc-Catalyzed Ring Expansion

by Hilan Z. Kaplan¹, Victor L. Rendina¹ and Jason S. Kingsbury^2,*

¹ Eugene F. Merkert Chemistry Center, Boston College, 2609 Beacon Street, Chestnut Hill, MA 02467, USA

² Ahmanson Science Center, California Lutheran University, 60 West Olsen Rd., Thousand Oaks, CA 91360, USA

Molecules 2017, 22(7), 1041; https://doi.org/10.3390/molecules22071041 - 24 Jun 2017

Cited by 6 | Viewed by 5795

Abstract

A stereocontrolled approach to the cis-decalin framework of clerodane diterpenes and biologically active quinone sesquiterpenes is reported. Starting from an inexpensive optically pure tetrahydroindanone, Birch reductive alkylation builds two new contiguous chiral centers—one of which is quaternary and all-carbon-substituted. Also featured is [...] Read more.

A stereocontrolled approach to the cis-decalin framework of clerodane diterpenes and biologically active quinone sesquiterpenes is reported. Starting from an inexpensive optically pure tetrahydroindanone, Birch reductive alkylation builds two new contiguous chiral centers—one of which is quaternary and all-carbon-substituted. Also featured is a highly regioselective diazoalkane—carbonyl homologation reaction to prepare the 6,6-bicyclic skeleton. Therein, the utility of Sc(OTf)₃ as a mild catalyst for formal 1C insertion in complex settings is demonstrated. Full article

(This article belongs to the Special Issue Asymmetric Synthesis 2017)

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Open AccessArticle

Antibacterial Effect of a 4x Cu-TiO₂ Coating Simulating Acute Periprosthetic Infection—An Animal Model

by Andreas Mauerer^1,2,*, Stefanie Stenglein³, Stefan Schulz-Drost⁴, Christoph Schoerner⁵, Dominic Taylor¹, Sebastian Krinner⁴, Frank Heidenau⁶, Werner Adler⁷ and Raimund Forst⁸

¹ Department of Trauma and Orthopaedic Surgery, St. Theresa-Hospital Nuremberg, Mommsenstr. 24, 90491 Nuremberg, Germany

² Biomechanics Laboratory-UO Lab, Department of Trauma and Orthopedic Surgery, University Hospital Erlangen Krankenhausstr. 12, 91054 Erlangen, Germany

³ Abteilung für Unfall-, Hand-, und Orthopädische Chirurgie, Sana Kliniken Solln Sendling, Plinganserstraße 122, 81369 München, Germany

⁴ Department of Trauma and Orthopedic Surgery, University Hospital Erlangen, Krankenhausstr. 12, 91054 Erlangen, Germany

⁵ Institute of Microbiology, Clinical Microbiology, Immunology and Hygiene, Universitätsklinikum Erlangen, Wasserturmstraße 35, 91054 Erlangen, Germany

⁶ BioCer Entwicklungs GmbH, Ludwig-Thoma-Straße 36, 95447 Bayreuth, Germany

⁷ Department of Medical Informatics, Biometry and Epidemiology, Friedrich-Alexander-University Erlangen-Nuremberg, Waldstr.6, 91054 Erlangen, Germany

⁸ Department of Orthopaedic Surgery, Friedrich-Alexander-University Erlangen-Nuremberg, Rathsbergerstr. 54, 91054 Erlangen, Germany

Molecules 2017, 22(7), 1042; https://doi.org/10.3390/molecules22071042 - 23 Jun 2017

Cited by 11 | Viewed by 5360

Abstract

The purpose of our study was to investigate the antibacterial effect of a spacer (Ti6Al4V) coated with 4x Cu-TiO₂ in an animal model simulating an acute periprosthetic infection by Staphylococcus aureus. Ti6Al4 bolts contaminated with Staphylococcus aureus were implanted into the [...] Read more.

The purpose of our study was to investigate the antibacterial effect of a spacer (Ti6Al4V) coated with 4x Cu-TiO₂ in an animal model simulating an acute periprosthetic infection by Staphylococcus aureus. Ti6Al4 bolts contaminated with Staphylococcus aureus were implanted into the femoral condyle of rabbits (n = 36) divided into 3 groups. After one week in group 1 (control) the bolts were removed without any replacement. In group2 Ti6Al4V bolts with a 4x Cu-TiO₂ coating and in group 3 beads of a gentamicin-PMMA chain were imbedded into the borehole. Microbiological investigation was performed at the primary surgery, at the revision surgery and after scarification of the rabbits 3 weeks after the first surgery. Blood tests were conducted weekly. The initial overall infection rate was 88.9%. In group 2 and 3 a significant decrease of the infection rate was shown in contrast to the control group. The C-reactive protein (CRP) levels declined one week after the first surgery except in the control group where the CRP level even increased. This is the first in vivo study that demonstrated the antibacterial effects of a fourfold Cu-TiO₂ coating. For the future, the coating investigated could be a promising option in the treatment of implant-associated infections. Full article

(This article belongs to the Special Issue Antibacterial Materials and Coatings)

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Open AccessArticle

Cellular Uptake and Delivery-Dependent Effects of Tb³⁺-Doped Hydroxyapatite Nanorods

by Yan Wei^1,†, Ying He^1,†, Xiyu Li², Haifeng Chen^2,* and Xuliang Deng^2,*

¹ Department of Geriatric Dentistry, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Laboratory of Biomedical Materials, Peking University School and Hospital of Stomatology, Peking University, Beijing 100081, China

² Department of Biomedical Engineering, College of Engineering, Peking University, 5 Yiheyuan Road, Haidian District, 100871 Beijing, China

^† These authors contributed equally to this work.

Molecules 2017, 22(7), 1043; https://doi.org/10.3390/molecules22071043 - 23 Jun 2017

Cited by 14 | Viewed by 4243

Abstract

With the increasing interest in hydroxyapatite (HA) nanostructures for use in biomedicine, the systematic evaluation of their potential effects on biological systems is becoming critically important. In this work, we report the in vitro cellular uptake, in vivo tissue distributions and toxicity of [...] Read more.

With the increasing interest in hydroxyapatite (HA) nanostructures for use in biomedicine, the systematic evaluation of their potential effects on biological systems is becoming critically important. In this work, we report the in vitro cellular uptake, in vivo tissue distributions and toxicity of Tb³⁺-doped HA (HA-Tb) after short-, intermediate-, and long-term exposure. Transmission electron microscopy analysis indicated that HA-Tb was taken up by cells via vesicle endocytosis. Cell proliferation and cytotoxicity assay, combined with confocal laser scanning microscopy, indicated excellent cell viability with no changes in cell morphology at the examined doses. Three HA-Tb delivery methods (intraperitoneal, intragastric, and intravenous) resulted in similar time-dependent tissue distributions, while intraperitoneal injection produced the highest bioavailability. HA-Tb initially accumulated in livers and intestines of rats (4 h to one day after administration), then became increasingly distributed in the kidney and bladder (seven days), and finally decreased in all tissues after 30 to 90 days. No histopathological abnormalities or lesions related to treatment with HA-Tb were observed. These results suggest that HA-Tb has minimal in vitro and in vivo toxicity, regardless of the delivery mode, time, and dose. The findings provide a foundation for the design and development of HA for biological applications. Full article

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Open AccessArticle

Osteoprotective Effect of Radix Scutellariae in Female Hindlimb-Suspended Sprague-Dawley Rats and the Osteogenic Differentiation Effect of Its Major Constituent

by Guangwei Zhang^1,2,†, Chenrui Li³, Yinbo Niu³, Qi Yu¹, Yulong Chen¹ and Enqi Liu^1,2,*

¹ Research Institute of Atherosclerotic Disease, College of Clinical Medicine, Xi’an Medical University, No.1Xinwang Road, Xi’an 710021, China

² Laboratory Animal Center, Xi′an Jiaotong University Health Science Center, Xi’an Jiaotong University, Xi’an 710061, China

³ Key Laboratory for Space Biosciences & Biotechnology, School of Life Sciences, Northwestern Polytechnical University, 127 Youyixi Road, Xi’an 710072, China

^† Current address: Shaanxi Key Laboratory of Ischemic Cardiovascular Disease, Department of Public Health, College of Clinical Medicine, Xi’an Medical University, Xi’an 710021, China.

Molecules 2017, 22(7), 1044; https://doi.org/10.3390/molecules22071044 - 3 Jul 2017

Cited by 17 | Viewed by 5156

Abstract

A number of medicinal herbs have demonstrated therapeutic effects for the prevention and treatment of disuse-induced osteoporosis. As a common ingredient in proprietary traditional Chinese medicines, the anti-osteoporosis effects of Radix Scutellariae extract (RSE, 50 mg/kg/day) were evaluated in a hindlimb suspended rat [...] Read more.

A number of medicinal herbs have demonstrated therapeutic effects for the prevention and treatment of disuse-induced osteoporosis. As a common ingredient in proprietary traditional Chinese medicines, the anti-osteoporosis effects of Radix Scutellariae extract (RSE, 50 mg/kg/day) were evaluated in a hindlimb suspended rat model. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry, and the micro-architecture observed by MicroCT assay with bone biomechanical properties evaluated by a three-point bending test. To elucidate potential mechanisms, the osteogenic differentiation effect of baicalin as the most abundant ingredient in RSE was investigated in rat bone marrow derived mesenchymal stem cells (rBMSC). After drug administration for 42 days, tibia-BMD was significantly increased to 0.176 ± 0.007 and 0.183 ± 0.011 g/cm² and f-BMD was enhanced to 0.200 ± 0.017 and 0.207 ± 0.021 g/cm² for RSE and ALE treatment, respectively, whereas tibia-BMD and femur-BMD of the HLS group were 0.157 ± 0.009 and 0.176 ± 0.008 g/cm². Deterioration of bone trabecula microstructure was improved by RSE and ALE with increased morphological parameters such as bone volume fraction, trabecular thickness, and trabecular number, as well as connectivity density compared to the HLS group (p < 0.01). A three-point bending test suggested that bone mechanical strength was also enhanced by RSE and ALE treatments with increased maximum stress, young’s modulus, maximum load, and stiffness compared to those of the HLS group (p < 0.05). Besides, serum TRACP levels were significantly suppressed by RSE and ALE treatments. Furthermore, in vitro studies demonstrated that baicalin significantly increased ALP activities and the formation of mineralized nodules in rBMSC. Conclusively, supplementation of RSE could significantly prevent weightlessness induced osteoporosis, which might attribute to the osteogenic differentiation enhancement effect of baicalin. Full article

(This article belongs to the Special Issue Herbal Remedies Meet Modern Day Medicine: Challenges and Opportunities)

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Open AccessArticle

Characterization of the Key Aroma Compounds in Chinese Syrah Wine by Gas Chromatography-Olfactometry-Mass Spectrometry and Aroma Reconstitution Studies

by Pengtao Zhao^1,†, Jinxin Gao^1,†, Michael Qian² and Hua Li^1,3,*

¹ College of Enology, Northwest A&F University, Yangling 712100, Shaanxi, China

² Department of Food Science & Technology, Oregon State University, Corvallis, OR 97333, USA

³ Shaanxi Engineering Research Center for Viti-Viniculture, Yangling 712100, Shaanxi, China

^† These authors contribute equally to this paper.

Molecules 2017, 22(7), 1045; https://doi.org/10.3390/molecules22071045 - 24 Jun 2017

Cited by 38 | Viewed by 7888

Abstract

The key aroma compounds and the organoleptic quality of two Chinese Syrah wines from the Yunnan Shangri-La region and Ningxia Helan mountain region were characterized. The most important eighty aroma-active compounds were identified by Gas Chromatography-Olfactometry. In both Syrah samples, ethyl 2-methylpropanoate, ethyl [...] Read more.

The key aroma compounds and the organoleptic quality of two Chinese Syrah wines from the Yunnan Shangri-La region and Ningxia Helan mountain region were characterized. The most important eighty aroma-active compounds were identified by Gas Chromatography-Olfactometry. In both Syrah samples, ethyl 2-methylpropanoate, ethyl 3-methylbutanoate, 3-methylbutyl acetate, 2- and 3-methyl-1-butanol, ethyl hexanoate, ethyl octanoate, 2-phenethyl acetate, methional, 3-methylbutanoic acid, hexanoic acid, octanoic acid, β-damascenone, guaiacol, 2-phenylethanol, trans-whiskylactone, 4-ethylguaiacol, eugenol, 4-ethylphenol, and sotolon were detected to have the highest odor intensities. In the chemical analysis, 72 compounds were quantitated by Stir Bar Sorptive Extraction combined with Gas Chromatography Mass Spectrometry. Based on the Odor Activity Value (OAV), the aromas were reconstituted by combining aroma compounds in the synthetic wine, and sensory descriptive analysis was used to verify the chemical data. Fatty acid ethyl esters, acetate esters, and β-damascenone were found with higher OAVs in the more fruity-smelling sample of Helan Mountain rather than Shangri-La. Full article

(This article belongs to the Collection Wine Chemistry)

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Open AccessReview

Use of Ultrasonication Technology for the Increased Production of Plant Secondary Metabolites

by Md. Mohidul Hasan, Tufail Bashir and Hanhong Bae^*

Department of Biotechnology, Yeungnam University, Gyeongsan 38541, Korea

Molecules 2017, 22(7), 1046; https://doi.org/10.3390/molecules22071046 - 23 Jun 2017

Cited by 39 | Viewed by 7456

Abstract

Plant secondary metabolites (PSMs) provide taste, color, odor, and resistance to plants, and they are also used to treat cancer and cardiovascular diseases. Synthesis of PSMs in plants is stimulated in response to different forms of external stress. Use of ultrasonication (US) to [...] Read more.

Plant secondary metabolites (PSMs) provide taste, color, odor, and resistance to plants, and they are also used to treat cancer and cardiovascular diseases. Synthesis of PSMs in plants is stimulated in response to different forms of external stress. Use of ultrasonication (US) to clean or decontaminate fruits and vegetables leads to physical stress that finally results in the accumulation of PSMs. US can stimulate accumulation of taxol, ginsenoside saponins, shikonin, and resveratrol, e.g., up to 319-fold increase of resveratrol synthesis has been observed in grape due to US. US also increases carotenoids, total phenolics, and isoflavonoids accumulation. Furthermore, US shows synergistic effects in PSMs synthesis-when combined with ultraviolet (UV) irradiation, jasmonic acid (JA) or salicylic acid (SA). It has been observed that US stimulates the production of reactive oxygen species (ROS) which then upregulates expression of phenylalanine ammonia lyase (PAL), resulting in the synthesis of PSMs. In this review, we summarize the effects of US, as a physical stress, to maximize the accumulation of PSMs in crop produce and in cell cultures. Full article

(This article belongs to the Section Metabolites)

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Open AccessArticle

The Investigation of Electrochemistry Behaviors of Tyrosinase Based on Directly-Electrodeposited Grapheneon Choline-Gold Nanoparticles

by Yaping He^1,*

, Xiaohui Yang¹, Quan Han^1,* and Jianbin Zheng²

¹ School of Chemical Engineering, Xi’an University, Xi’an 710065, China

² Institute of Analytical Science/Shaanxi Provincial Key Laboratory of Electroanalytical Chemistry, Northwest University, Xi’an 710069, China

Molecules 2017, 22(7), 1047; https://doi.org/10.3390/molecules22071047 - 23 Jun 2017

Cited by 6 | Viewed by 4940

Abstract

A novel catechol (CA) biosensor was developed by embedding tyrosinase (Tyr) onto in situ electrochemical reduction graphene (EGR) on choline-functionalized gold nanoparticle (AuNPs-Ch) film. The results of UV-Vis spectra indicated that Tyr retained its original structure in the film, and an electrochemical investigation [...] Read more.

A novel catechol (CA) biosensor was developed by embedding tyrosinase (Tyr) onto in situ electrochemical reduction graphene (EGR) on choline-functionalized gold nanoparticle (AuNPs-Ch) film. The results of UV-Vis spectra indicated that Tyr retained its original structure in the film, and an electrochemical investigation of the biosensor showed a pair of well-defined, quasi-reversible redox peaks with E_pa = −0.0744 V and E_pc = −0.114 V (vs. SCE) in 0.1 M, pH 7.0 sodium phosphate-buffered saline at a scan rate of 100 mV/s. The transfer rate constant k_s is 0.66 s⁻¹. The Tyr-EGR/AuNPs-Ch showed a good electrochemical catalytic response for the reduction of CA, with the linear range from 0.2 to 270 μM and a detection limit of 0.1 μM (S/N = 3). The apparent Michaelis-Menten constant was estimated to be 109 μM. Full article

(This article belongs to the Section Organometallic Chemistry)

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Open AccessReview

Recent Progress in Nanomaterial-Based Electrochemical Biosensors for Cancer Biomarkers: A Review

by Baozhen Wang¹, Uichi Akiba² and Jun-ichi Anzai^3,*

¹ Department of Nutrition and Food Hygiene, School of Public Health, Shandong University, 44 Wenhua Xilu, Jinan 250012, China

² Graduate School of Engineering and Science, Akita University, 1-1 Tegatagakuen-machi, Akita 010-8502, Japan

³ Graduate School of Pharmaceutical Sciences, Tohoku University, Aramaki, Aoba-ku, Sendai 980-8578, Japan

Molecules 2017, 22(7), 1048; https://doi.org/10.3390/molecules22071048 - 24 Jun 2017

Cited by 101 | Viewed by 9874

Abstract

This article reviews recent progress in the development of nanomaterial-based electrochemical biosensors for cancer biomarkers. Because of their high electrical conductivity, high affinity to biomolecules, and high surface area-to-weight ratios, nanomaterials, including metal nanoparticles, carbon nanotubes, and graphene, have been used for fabricating [...] Read more.

This article reviews recent progress in the development of nanomaterial-based electrochemical biosensors for cancer biomarkers. Because of their high electrical conductivity, high affinity to biomolecules, and high surface area-to-weight ratios, nanomaterials, including metal nanoparticles, carbon nanotubes, and graphene, have been used for fabricating electrochemical biosensors. Electrodes are often coated with nanomaterials to increase the effective surface area of the electrodes and immobilize a large number of biomolecules such as enzymes and antibodies. Alternatively, nanomaterials are used as signaling labels for increasing the output signals of cancer biomarker sensors, in which nanomaterials are conjugated with secondary antibodies and redox compounds. According to this strategy, a variety of biosensors have been developed for detecting cancer biomarkers. Recent studies show that using nanomaterials is highly advantageous in preparing high-performance biosensors for detecting lower levels of cancer biomarkers. This review focuses mainly on the protocols for using nanomaterials to construct cancer biomarker sensors and the performance characteristics of the sensors. Recent trends in the development of cancer biomarker sensors are discussed according to the nanomaterials used. Full article

(This article belongs to the Special Issue Supramolecular Chemistry and Self-Assembly: Themed Issue in Honor of Professor Itamar Willner on the Occasion of His 70th Birthday)

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Open AccessArticle

Novel Sulfamide-Containing Compounds as Selective Carbonic Anhydrase I Inhibitors

by Emanuela Berrino^1,†

, Silvia Bua^1,†

, Mattia Mori², Maurizio Botta^2,3, Vallabhaneni S. Murthy⁴, Vijayaparthasarathi Vijayakumar⁴, Yasinalli Tamboli^4,*, Gianluca Bartolucci¹

, Alessandro Mugelli⁵, Elisabetta Cerbai⁵, Claudiu T. Supuran^1,*

and Fabrizio Carta^1,*

¹ NEUROFARBA Department, Sezione di Scienze Farmaceutiche e Nutraceutiche, Università degli Studi di Firenze, Via Ugo Schiff 6, 50019 Sesto Fiorentino (Florence), Italy

² Department of Biotechnology, Chemistry and Pharmacy, University of Siena, viale Aldo Moro 2, 53100 Siena, Italy

³ Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, College of Science 1.and Technology, Temple University, BioLife Science Building, Suite 333, 1900 N 12th Street, Philadelphia, PA 19122, USA

⁴ Center for Organic and Medicinal Chemistry, School of Advanced Sciences, VIT University, Vellore, 632014 Tamil Nadu, India

⁵ Department of Neurosciences, Psychology, Drug’s Research and Child’s Health (NEUROFARBA), University of Florence, Italy; Section of Pharmacology and Toxicology, viale Pieraccini 6, 50100 Firenze, Italy

^† These authors contributed equally.

Molecules 2017, 22(7), 1049; https://doi.org/10.3390/molecules22071049 - 24 Jun 2017

Cited by 27 | Viewed by 6573

Abstract

The development of isoform selective inhibitors of the carbonic anhydrase (CA; EC 4.2.1.1) enzymes represents the key approach for the successful development of druggable small molecules. Herein we report a series of new benzenesulfamide derivatives (-NH-SO₂NH₂) bearing the 1-benzhydrylpiperazine [...] Read more.

The development of isoform selective inhibitors of the carbonic anhydrase (CA; EC 4.2.1.1) enzymes represents the key approach for the successful development of druggable small molecules. Herein we report a series of new benzenesulfamide derivatives (-NH-SO₂NH₂) bearing the 1-benzhydrylpiperazine tail and connected by means of a β-alanyl or nipecotyl spacer. All compounds 6a–l were investigated in vitro for their ability to inhibit the physiological relevant human (h) CA isoforms such as I, II, IV and IX. Molecular modeling provided further structural support to enzyme inhibition data and structure-activity relationship. In conclusion the hCA I resulted the most inhibited isoform, whereas all the remaining ones showed different inhibition profiles. Full article

(This article belongs to the Special Issue Sulfonamides)

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Open AccessArticle

Myrtaceae Plant Essential Oils and their β-Triketone Components as Insecticides against Drosophila suzukii

by Chung Gyoo Park^1,2, Miyeon Jang², Eunsik Shin^2,† and Junheon Kim^3,*

¹ Institute of Agriculture and Life Science, Gyeongsang National University, Jinju 52828, Korea

² Division of Applied Life Science (BK21+ Program), Gyeongsang National University, Jinju 52828, Korea

³ Forest Insect Pests and Diseases Division, National Institute of Forest Science, Seoul 02455, Korea

^† Present address: R&D Bio Team, Agrigento Co., Ltd, Geochang, Gyeongsangnamdo 50119, Korea

Molecules 2017, 22(7), 1050; https://doi.org/10.3390/molecules22071050 - 24 Jun 2017

Cited by 31 | Viewed by 7512

Abstract

Spotted wing drosophila (SWD, Drosophila suzukii (Matsumura), Diptera: Drosophilidae) is recognized as an economically important pest in North America and Europe as well as in Asia. Assessments were made for fumigant and contact toxicities of six Myrtaceae plant essential oils (EOs) and their [...] Read more.

Spotted wing drosophila (SWD, Drosophila suzukii (Matsumura), Diptera: Drosophilidae) is recognized as an economically important pest in North America and Europe as well as in Asia. Assessments were made for fumigant and contact toxicities of six Myrtaceae plant essential oils (EOs) and their components to find new alternative types of insecticides active against SWD. Among the EOs tested, Leptospermum citratum EO, consisting mainly of geranial and neral, exhibited effective fumigant activity. Median lethal dose (LD₅₀;mg/L) values of L. citratum were 2.39 and 3.24 for males and females, respectively. All tested EOs except Kunzea ambigua EO exhibited effective contact toxicity. LD₅₀ (µg/fly) values for contact toxicity of manuka and kanuka were 0.60 and 0.71, respectively, for males and 1.10 and 1.23, respectively, for females. The LD₅₀ values of the other 3 EOs-L. citratum, allspice and clove bud were 2.11–3.31 and 3.53–5.22 for males and females, respectively. The non-polar fraction of manuka and kanuka did not show significant contact toxicity, whereas the polar and triketone fractions, composed of flavesone, isoleptospermone and leptospermone, exhibited efficient activity with the LD₅₀ values of 0.13–0.37 and 0.22–0.57 µg/fly for males and females, respectively. Our results indicate that Myrtaceae plant EOs and their triketone components can be used as alternatives to conventional insecticides. Full article

(This article belongs to the Section Natural Products Chemistry)

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Open AccessArticle

Structural Characterization of the Low-Molecular-Weight Heparin Dalteparin by Combining Different Analytical Strategies

by Antonella Bisio^1,*, Elena Urso¹, Marco Guerrini¹, Pauline De Wit^1,2,†, Giangiacomo Torri¹ and Annamaria Naggi¹

¹ Istituto di Ricerche Chimiche e Biochimiche G. Ronzoni, 20133 Milan, Italy

² Department of Cell and Applied Biology, Faculty of Science, Radboud University Nijmegen, 6525 HP Nijmegen, The Netherlands

^† Current address: Aspen Oss B.V., Kloosterstraat 6, 5349 AB Oss, Netherlands.

Molecules 2017, 22(7), 1051; https://doi.org/10.3390/molecules22071051 - 24 Jun 2017

Cited by 16 | Viewed by 6786

Abstract

A number of low molecular weight heparin (LMWH) products are available for clinical use and although all share a similar mechanism of action, they are classified as distinct drugs because of the different depolymerisation processes of the native heparin resulting in substantial pharmacokinetic [...] Read more.

A number of low molecular weight heparin (LMWH) products are available for clinical use and although all share a similar mechanism of action, they are classified as distinct drugs because of the different depolymerisation processes of the native heparin resulting in substantial pharmacokinetic and pharmacodynamics differences. While enoxaparin has been extensively investigated, little information is available regarding the LMWH dalteparin. The present study is focused on the detailed structural characterization of Fragmin^® by LC-MS and NMR applied both to the whole drug and to its enzymatic products. For a more in-depth approach, size homogeneous octasaccharide and decasaccharide components together with their fractions endowed with high or no affinity toward antithrombin were also isolated and their structural profiles characterized. The combination of different analytical strategies here described represents a useful tool for the assessment of batch-to-batch structural variability and for comparative evaluation of structural features of biosimilar products. Full article

(This article belongs to the Special Issue Looking Forward to the Future of Heparin: New Sources, Developments and Applications)

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Open AccessArticle

Augmented Anticancer Effects of Cantharidin with Liposomal Encapsulation: In Vitro and In Vivo Evaluation

by Xue Zhang¹, Cong-Cong Lin¹, Wai-Kei-Nickie Chan¹, Kang-Lun Liu¹, Zhi-Jun Yang^1,2,* and Hong-Qi Zhang^1,*

¹ School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China

² Changshu Research Institute, Hong Kong Baptist University, Changshu Economic and Technological Development (CETD) Zone, Changshu 215500, China

Molecules 2017, 22(7), 1052; https://doi.org/10.3390/molecules22071052 - 24 Jun 2017

Cited by 14 | Viewed by 6211

Abstract

PEGylated liposomes have received much attention as pharmaceutical carriers to deliver chemotherapeutic agents for therapeutic purpose. The aim of this study was to prepare and characterize PEGylated liposome of cantharidin and investigate its therapeutic effect on human hepatocellular carcinoma treatment in vitro and [...] Read more.

PEGylated liposomes have received much attention as pharmaceutical carriers to deliver chemotherapeutic agents for therapeutic purpose. The aim of this study was to prepare and characterize PEGylated liposome of cantharidin and investigate its therapeutic effect on human hepatocellular carcinoma treatment in vitro and in vivo. Liposomal cantharidin was evaluated for their anticancer effects in vitro using human hepatocellular carcinoma HepG2 cells and in vivo using HepG2-bearing nude mice compared to free drug. PEGylated liposome of cantharidin had a particle size of 129.9 nm and a high encapsulation efficacy of approximately 88.9%. The liposomal cantharidin had a higher anti-proliferative effect vis-à-vis free cantharidin in inducing G2/M cell cycle arrest and apoptosis. Liposomal cantharidin killed more HepG2 cancer cells at the same concentration equivalent to free cantharidin. Further study in vivo also showed that liposomal cantharidin achieved a higher tumor growth inhibition efficacy than free drug on hepatocellular carcinoma. As our study exhibited enhanced cytotoxicity against HepG2 cells and augmented tumor inhibitory effects in vivo, the results validate the potential value of cantharidin-liposome in improving the therapeutic efficacy of cantharidin for liver cancer. Full article

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Open AccessArticle

Eu@C₇₂: Computed Comparable Populations of Two Non-IPR Isomers

by Zdeněk Slanina^1,*, Filip Uhlík², Shigeru Nagase³, Takeshi Akasaka¹, Ludwik Adamowicz⁴ and Xing Lu¹

¹ State Key Laboratory of Materials Processing and Die & Mould Technology, School of Material Science and Engineering, Huazhong University of Science and Technology, Wuhan 430074, China

² Department of Physical and Macromolecular Chemistry, Faculty of Science, Charles University, Albertov 6, 128 43 Praha 2, Czech Republic

³ Fukui Institute for Fundamental Chemistry, Kyoto University, Kyoto 606-8103, Japan

⁴ Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ 85721-0041, USA

Molecules 2017, 22(7), 1053; https://doi.org/10.3390/molecules22071053 - 24 Jun 2017

Cited by 24 | Viewed by 4059

Abstract

Relative concentrations of six isomeric Eu@C

_{72}

—one based on the IPR C

_{72}

cage (i.e., obeying the isolated-pentagon rule, IPR), two cages with a pentagon–pentagon junction (symmetries

C_{2}

and

C_{2 v}

), a cage with one heptagon, a cage with [...] Read more.

Relative concentrations of six isomeric Eu@C

_{72}

—one based on the IPR C

_{72}

cage (i.e., obeying the isolated-pentagon rule, IPR), two cages with a pentagon–pentagon junction (symmetries

C_{2}

and

C_{2 v}

), a cage with one heptagon, a cage with two heptagons, and a cage with two pentagon–pentagon fusions—are DFT computed using the Gibbs energy in a broad temperature interval. It is shown that the two non-IPR isomers with one pentagon–pentagon junction prevail at any relevant temperature and exhibit comparable populations. The IPR-satisfying structure is disfavored by both energy and entropy. Full article

(This article belongs to the Special Issue Endohedral Metallofullerenes)

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Open AccessArticle

Rational Design of Cyclic Antimicrobial Peptides Based on BPC194 and BPC198

by Anna D. Cirac^1,2, Maria Torné¹, Esther Badosa³, Emilio Montesinos³

, Pedro Salvador^2,*, Lidia Feliu^1,*

and Marta Planas^1,*

¹ LIPPSO, Departament de Química, University of Girona, Maria Aurèlia Capmany 69, 17003 Girona, Spain

² Institut de Química Computacional i Catàlisi i Departament de Química, University of Girona, Maria Aurèlia Capmany 69, 17003 Girona, Spain

³ Laboratory of Plant Pathology, Institute of Food and Agricultural Technology-CIDSAV-XaRTA, University of Girona, Maria Aurèlia Capmany 61, 17003 Girona, Spain

Molecules 2017, 22(7), 1054; https://doi.org/10.3390/molecules22071054 - 24 Jun 2017

Cited by 14 | Viewed by 5672

Abstract

A strategy for the design of antimicrobial cyclic peptides derived from the lead compounds c(KKLKKFKKLQ) (BPC194) and c(KLKKKFKKLQ) (BPC198) is reported. First, the secondary β-structure of BPC194 and BPC198 was analyzed by carrying out molecular dynamics (MD) simulations. Then, [...] Read more.

A strategy for the design of antimicrobial cyclic peptides derived from the lead compounds c(KKLKKFKKLQ) (BPC194) and c(KLKKKFKKLQ) (BPC198) is reported. First, the secondary β-structure of BPC194 and BPC198 was analyzed by carrying out molecular dynamics (MD) simulations. Then, based on the sequence pattern and the β-structure of BPC194 or BPC198, fifteen analogues were designed and synthesized on solid-phase. The best peptides (BPC490, BPC918, and BPC924) showed minimum inhibitory concentration (MIC) values <6.2 μM against Pseudomonas syringae pv. syringae and Xanthomonas axonopodis pv. vesicatoria, and an MIC value of 12.5 to 25 μM against Erwinia amylovora, being as active as BPC194 and BPC198. Interestingly, these three analogues followed the structural pattern defined from the MD simulations of the parent peptides. Thus, BPC490 maintained the parallel alignment of the hydrophilic pairs K¹–K⁸, K²–K⁷, and K⁴–K⁵, whereas BPC918 and BPC924 included the two hydrophilic interactions K³–Q¹⁰ and K⁵–K⁸. In short, MD simulations have proved to be very useful for ascertaining the structural features of cyclic peptides that are crucial for their biological activity. Such approaches could be further employed for the development of new antibacterial cyclic peptides. Full article

(This article belongs to the Special Issue Peptide-Based Drugs and Drug Delivery Systems)

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Open AccessArticle

Improved Method for Reliable HMW-GS Identification by RP-HPLC and SDS-PAGE in Common Wheat Cultivars

by You-Ran Jang^1,†, Hye-Rang Beom^1,†, Susan B. Altenbach², Min-Ki Lee¹, Sun-Hyung Lim¹ and Jong-Yeol Lee^1,*

¹ National Institute of Agricultural Science, RDA, Jeonju 54874, Korea

² USDA-ARS, Western Regional Research Center, 800 Buchanan Street, Albany, CA 94710, USA

^† These authors contributed equally to this work.

Molecules 2017, 22(7), 1055; https://doi.org/10.3390/molecules22071055 - 24 Jun 2017

Cited by 25 | Viewed by 5591

Abstract

The accurate identification of alleles for high-molecular weight glutenins (HMW-GS) is critical for wheat breeding programs targeting end-use quality. RP-HPLC methods were optimized for separation of HMW-GS, resulting in enhanced resolution of 1By and 1Dx subunits. Statistically significant differences in retention times (RTs) [...] Read more.

The accurate identification of alleles for high-molecular weight glutenins (HMW-GS) is critical for wheat breeding programs targeting end-use quality. RP-HPLC methods were optimized for separation of HMW-GS, resulting in enhanced resolution of 1By and 1Dx subunits. Statistically significant differences in retention times (RTs) for subunits corresponding to HMW-GS alleles were determined using 16 standard wheat cultivars with known HMW-GS compositions. Subunits that were not identified unambiguously by RP-HPLC were distinguished by SDS-PAGE or inferred from association with linked subunits. The method was used to verify the allelic compositions of 32 Korean wheat cultivars previously determined using SDS-PAGE and to assess the compositions of six new Korean cultivars. Three cultivars contained subunits that were identified incorrectly in the earlier analysis. The improved RP-HPLC method combined with conventional SDS-PAGE provides for accurate, efficient and reliable identification of HMW-GS and will contribute to efforts to improve wheat end-use quality. Full article

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Open AccessArticle

Solvent-Free Microwave-Assisted Extraction of Polyphenols from Olive Tree Leaves: Antioxidant and Antimicrobial Properties

by Selin Şahin¹

, Ruya Samli², Ayşe Seher Birteksöz Tan³, Francisco J. Barba⁴

, Farid Chemat⁵

, Giancarlo Cravotto^6,*

and José M. Lorenzo⁷

¹ Department of Chemical Engineering, Engineering Faculty, Istanbul University, 34320 Avcilar, Istanbul, Turkey

² Department of Computer Engineering, Engineering Faculty, Istanbul University, 34320 Avcilar, Istanbul, Turkey

³ Department of Pharmaceutical Microbiology, Faculty of Pharmacy, Istanbul University, 34116 Beyazıt, Istanbul, Turkey

⁴ Nutrition and Food Science Area, Preventive Medicine and Public Health, Food Science, Toxicology and Forensic Medicine Department, Faculty of Pharmacy, Universitat de València, Avda. Vicent Andrés Estellés, s/n, 46100 Burjassot, València, Spain

⁵ Avignon University, INRA, Green Extraction Team, 84916Avignon, France

⁶ Dipartimento di Scienza e Tecnologia del Farmaco, University of Turin, Via P. Giuria 9, 10125 Turin, Italy

⁷ Centro Tecnológico de la Carne de Galicia, c/ Galicia, 4, 32900 San Ciprián de Viñas, Ourense, Spain

Molecules 2017, 22(7), 1056; https://doi.org/10.3390/molecules22071056 - 24 Jun 2017

Cited by 155 | Viewed by 11675

Abstract

Response surface methodology (RSM) and artificial neural networks (ANN) were evaluated and compared in order to decide which method was the most appropriate to predict and optimize total phenolic content (TPC) and oleuropein yields in olive tree leaf (Olea europaea) extracts, [...] Read more.

Response surface methodology (RSM) and artificial neural networks (ANN) were evaluated and compared in order to decide which method was the most appropriate to predict and optimize total phenolic content (TPC) and oleuropein yields in olive tree leaf (Olea europaea) extracts, obtained after solvent-free microwave-assisted extraction (SFMAE). The SFMAE processing conditions were: microwave irradiation power 250–350 W, extraction time 2–3 min, and the amount of sample 5–10 g. Furthermore, the antioxidant and antimicrobial activities of the olive leaf extracts, obtained under optimal extraction conditions, were assessed by several in vitro assays. ANN had better prediction performance for TPC and oleuropein yields compared to RSM. The optimum extraction conditions to recover both TPC and oleuropein were: irradiation power 250 W, extraction time 2 min, and amount of sample 5 g, independent of the method used for prediction. Under these conditions, the maximal yield of oleuropein (0.060 ± 0.012 ppm) was obtained and the amount of TPC was 2.480 ± 0.060 ppm. Moreover, olive leaf extracts obtained under optimum SFMAE conditions showed antibacterial activity against S. aureus and S. epidermidis, with a minimum inhibitory concentration (MIC) value of 1.25 mg/mL. Full article

(This article belongs to the Special Issue Green Extraction of Natural Product: Innovative Techniques, Alternative Solvents and Original Procedures)

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Open AccessReview

Recent Advances in Conotoxin Classification by Using Machine Learning Methods

by Fu-Ying Dao¹, Hui Yang¹, Zhen-Dong Su¹, Wuritu Yang^1,2, Yun Wu³, Ding Hui¹, Wei Chen^1,4,*, Hua Tang^5,* and Hao Lin^1,*

¹ Key Laboratory for Neuro-Information of Ministry of Education, School of Life Science and Technology, Center for Informational Biology, University of Electronic Science and Technology of China, Chengdu 610054, China

² Development and Planning Department, Inner Mongolia University, Hohhot 010021, China

³ College of Computer and Information Engineering, Xiamen University of Technology, Xiamen 361024, China

⁴ Department of Physics, School of Sciences, and Center for Genomics and Computational Biology, North China University of Science and Technology, Tangshan 063000, China

⁵ Department of Pathophysiology, Southwest Medical University, Luzhou 646000, China

Molecules 2017, 22(7), 1057; https://doi.org/10.3390/molecules22071057 - 25 Jun 2017

Cited by 54 | Viewed by 9223

Abstract

Conotoxins are disulfide-rich small peptides, which are invaluable peptides that target ion channel and neuronal receptors. Conotoxins have been demonstrated as potent pharmaceuticals in the treatment of a series of diseases, such as Alzheimer’s disease, Parkinson’s disease, and epilepsy. In addition, conotoxins are [...] Read more.

Conotoxins are disulfide-rich small peptides, which are invaluable peptides that target ion channel and neuronal receptors. Conotoxins have been demonstrated as potent pharmaceuticals in the treatment of a series of diseases, such as Alzheimer’s disease, Parkinson’s disease, and epilepsy. In addition, conotoxins are also ideal molecular templates for the development of new drug lead compounds and play important roles in neurobiological research as well. Thus, the accurate identification of conotoxin types will provide key clues for the biological research and clinical medicine. Generally, conotoxin types are confirmed when their sequence, structure, and function are experimentally validated. However, it is time-consuming and costly to acquire the structure and function information by using biochemical experiments. Therefore, it is important to develop computational tools for efficiently and effectively recognizing conotoxin types based on sequence information. In this work, we reviewed the current progress in computational identification of conotoxins in the following aspects: (i) construction of benchmark dataset; (ii) strategies for extracting sequence features; (iii) feature selection techniques; (iv) machine learning methods for classifying conotoxins; (v) the results obtained by these methods and the published tools; and (vi) future perspectives on conotoxin classification. The paper provides the basis for in-depth study of conotoxins and drug therapy research. Full article

(This article belongs to the Special Issue Computational Analysis for Protein Structure and Interaction)

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Open AccessArticle

Influence of Pyranose and Spacer Arm Structures on Phloem Mobility and Insecticidal Activity of New Tralopyril Derivatives

by Yao Chen^1,2,3, Zhi Wei Lei³, Ying Zhang⁴, Wen Yang³, Hui Fang Liu³, Yu Feng Zhou³ and Mao Fa Yang^1,2,*

¹ Institute of Entomology, Guizhou University, Guiyang 550025, Guizhou, China

² Guizhou Provincial Key Laboratory for Agricultural Pest Management of the Mountainous Region, Guizhou University, Guiyang 550025, Guizhou, China

³ Guizhou Tea Research Institute, Guizhou Academy of Agricultural Sciences, Guiyang 550006, Guizhou, China

⁴ Guizhou Institute of Plant Protection, Guizhou Academy of Agricultural Sciences, Guiyang 550006, Guizhou, China

Molecules 2017, 22(7), 1058; https://doi.org/10.3390/molecules22071058 - 25 Jun 2017

Cited by 13 | Viewed by 4608

Abstract

Six new conjugates were designed and synthesized by introducing glucose, methyl glucuronate or glucuronic acid moieties on tralopyril. Phytotoxicity and phloem mobility results demonstrated that the introduction of glucose, methyl glucuronate or glucuronic acid moieties can simultaneously solve the tough phytotoxicity problem and [...] Read more.

Six new conjugates were designed and synthesized by introducing glucose, methyl glucuronate or glucuronic acid moieties on tralopyril. Phytotoxicity and phloem mobility results demonstrated that the introduction of glucose, methyl glucuronate or glucuronic acid moieties can simultaneously solve the tough phytotoxicity problem and phloem mobility transformation of tralopyril. Conjugates 12 and 18 containing the glucuronic acid moiety exhibited higher phloem mobility than conjugates 9, 11, 15 and 17. Conjugates 15, 17 and 18 with methoxymethyl groups on the tralopyril pyrrole nitrogen atom showed activity against Plutella xylostella, while conjugates 9, 11 and 12 with a methene group on the pyrrole N showed no activity. Cabbage roots were incubated in a buffered solution containing conjugates 15, 17 and 18 at 4 mM for 72 h. Only 18 showed systemic insecticidal activity with 100% mortalityagainst P. xylostella, while 15 and 17 showed lower activity andchlorfenapyr showed no activity. The glucuronic acid promoiety imparted more phloem mobility to tralopyril than glucose and methyl glucuronate. The methoxymethyl group bond on the tralopyril skeleton was the key factor in determining the insecticidal activity of the conjugates. A promising systemic proinsecticide containing glucuronic acid and tralopyril moieties was proposed. Full article

(This article belongs to the Section Organic Chemistry)

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Open AccessArticle

Calculation of Five Thermodynamic Molecular Descriptors by Means of a General Computer Algorithm Based on the Group-Additivity Method: Standard Enthalpies of Vaporization, Sublimation and Solvation, and Entropy of Fusion of Ordinary Organic Molecules and Total Phase-Change Entropy of Liquid Crystals

by Rudolf Naef^1,*

and William E. Acree²

¹ Department of Chemistry, University of Basel, Basel 4003, Switzerland

² Department of Chemistry, University of North Texas, Denton, TX 76203, USA

Molecules 2017, 22(7), 1059; https://doi.org/10.3390/molecules22071059 - 25 Jun 2017

Cited by 46 | Viewed by 7409

Abstract

The calculation of the standard enthalpies of vaporization, sublimation and solvation of organic molecules is presented using a common computer algorithm on the basis of a group-additivity method. The same algorithm is also shown to enable the calculation of their entropy of fusion [...] Read more.

The calculation of the standard enthalpies of vaporization, sublimation and solvation of organic molecules is presented using a common computer algorithm on the basis of a group-additivity method. The same algorithm is also shown to enable the calculation of their entropy of fusion as well as the total phase-change entropy of liquid crystals. The present method is based on the complete breakdown of the molecules into their constituting atoms and their immediate neighbourhood; the respective calculations of the contribution of the atomic groups by means of the Gauss-Seidel fitting method is based on experimental data collected from literature. The feasibility of the calculations for each of the mentioned descriptors was verified by means of a 10-fold cross-validation procedure proving the good to high quality of the predicted values for the three mentioned enthalpies and for the entropy of fusion, whereas the predictive quality for the total phase-change entropy of liquid crystals was poor. The goodness of fit (Q²) and the standard deviation (σ) of the cross-validation calculations for the five descriptors was as follows: 0.9641 and 4.56 kJ/mol (N = 3386 test molecules) for the enthalpy of vaporization, 0.8657 and 11.39 kJ/mol (N = 1791) for the enthalpy of sublimation, 0.9546 and 4.34 kJ/mol (N = 373) for the enthalpy of solvation, 0.8727 and 17.93 J/mol/K (N = 2637) for the entropy of fusion and 0.5804 and 32.79 J/mol/K (N = 2643) for the total phase-change entropy of liquid crystals. The large discrepancy between the results of the two closely related entropies is discussed in detail. Molecules for which both the standard enthalpies of vaporization and sublimation were calculable, enabled the estimation of their standard enthalpy of fusion by simple subtraction of the former from the latter enthalpy. For 990 of them the experimental enthalpy-of-fusion values are also known, allowing their comparison with predictions, yielding a correlation coefficient R² of 0.6066. Full article

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Open AccessArticle

In silico Study of the Pharmacologic Properties and Cytotoxicity Pathways in Cancer Cells of Various Indolylquinone Analogues of Perezone

by René Escobedo-González¹

, Claudia Lucia Vargas-Requena², Edgar Moyers-Montoya³, Juan Manuel Aceves-Hernández¹

, María Inés Nicolás-Vázquez^1,* and René Miranda-Ruvalcaba¹

¹ Departamento de Ciencias Químicas, Facultad de Estudios Superiores Cuautitlán, Universidad Nacional Autónoma de México, Cuautitlán Izcalli, Estado de México, C.P. 54740, México

² Instituto de Ciencias Biomédicas, Universidad Autónoma de Ciudad Juárez, Henry Dunant #4600, Ciudad Juárez 32310, México

³ Instituto de Ingeniería y tecnología, Universidad Autónoma de Ciudad Juárez, Ave. Del Charro 450 Norte, Ciudad Juárez 32310, México

Molecules 2017, 22(7), 1060; https://doi.org/10.3390/molecules22071060 - 25 Jun 2017

Cited by 18 | Viewed by 5803

Abstract

Several indolylquinone analogues of perezone, a natural sesquiterpene quinone, were characterized in this work by theoretical methods. In addition, some physicochemical, toxicological and metabolic properties were predicted using bioinformatics software. The predicted physicochemical properties are in agreement with the solubility and cLogP values, [...] Read more.

Several indolylquinone analogues of perezone, a natural sesquiterpene quinone, were characterized in this work by theoretical methods. In addition, some physicochemical, toxicological and metabolic properties were predicted using bioinformatics software. The predicted physicochemical properties are in agreement with the solubility and cLogP values, the penetration across the cell membrane, and absorption values, as well as with a possible apoptosis-activated mechanism of cytotoxic action. The toxicological predictions suggest no mutagenic, tumorigenic or reproductive effects of the four target molecules. Complementarily, the results of a performed docking study show high scoring values and hydrogen bonding values in agreement with the cytotoxicity IC₅₀ value ranking, i.e: indolylmenadione > indolylperezone > indolylplumbagine > indolylisoperezone. Consequently, it is possible to suggest an appropriate apoptotic pathway for each compound. Finally, potential metabolic pathways of the molecules were proposed. Full article

(This article belongs to the Special Issue The Biomedical Importance of Indoles and Their Derivatives)

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Open AccessArticle

Magnetic Solid-phase Extraction with Fe₃O₄/Molecularly Imprinted Polymers Modified by Deep Eutectic Solvents and Ionic Liquids for the Rapid Purification of Alkaloid Isomers (Theobromine and Theophylline) from Green Tea

by Guizhen Li, Xiaoqin Wang and Kyung Ho Row^*

Department of Chemistry and Chemical Engineering, Inha University, Incheon 402751, Korea

Molecules 2017, 22(7), 1061; https://doi.org/10.3390/molecules22071061 - 25 Jun 2017

Cited by 51 | Viewed by 8112

Abstract

Different kinds of deep eutectic solvents (DES) based on choline chloride (ChCl) and ionic liquids (ILs) based on 1-methylimidazole were used to modify Fe3O4/molecularly imprinted polymers (Fe3O4/MIPs), and the resulting materials were applied for the rapid purification of alkaloid isomers (theobromine and theophylline) [...] Read more.

Different kinds of deep eutectic solvents (DES) based on choline chloride (ChCl) and ionic liquids (ILs) based on 1-methylimidazole were used to modify Fe3O4/molecularly imprinted polymers (Fe3O4/MIPs), and the resulting materials were applied for the rapid purification of alkaloid isomers (theobromine and theophylline) from green tea with magnetic solid-phase extraction (M-SPE). The M-SPE procedure was optimized using the response surface methodology (RSM) to analyze the maximum conditions. The materials were characterized by Fourier transform infrared spectroscopy (FI-IR) and field emission scanning electron microscopy (FE-SEM). Compared to the ILs-Fe3O4/MIPs, the DESs-Fe3O4/MIPs were developed for the stronger recognition and higher recoveries of the isomers (theophylline and theobromine) from green tea, particularly DES-7-Fe3O4/MIPs. With RSM, the optimal recovery condition for theobromine and theophylline in the M-SPE were observed with ratio of methanol (80%) as the washing solution, methanol/acetic acid (HAc) (8:2) as the eluent at pH 3, and an eluent volume of 4 mL. The practical recoveries of theobromine and theophylline in green tea were 92.27% and 87.51%, respectively, with a corresponding actual extraction amount of 4.87 mg•g−1 and 5.07 mg•g−1. Overall, the proposed approach with the high affinity of Fe3O4/MIPs might offer a novel method for the purification of complex isomer samples. Full article

(This article belongs to the Special Issue Green Extraction of Natural Product: Innovative Techniques, Alternative Solvents and Original Procedures)

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Open AccessArticle

Calcineurin Antagonizes AMPK to Regulate Lipolysis in Caenorhabditis elegans

by Yanli Wang^1,†

, Cangsang Xie^1,2,†, Zhiqing Diao^1,3 and Bin Liang^1,*

¹ Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China

² Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming 650204, China

³ School of Life Sciences, Anhui University, Hefei 230601, China

^† These authors contributed equally to this work.

Molecules 2017, 22(7), 1062; https://doi.org/10.3390/molecules22071062 - 26 Jun 2017

Cited by 9 | Viewed by 6234

Abstract

Calcineurin is a calcium- and calmodulin-dependent serine/threonine protein phosphatase, and the target of immunosuppressive agent tacrolimus (TAC). The dysfunction of calcineurin, or clinical applications of tacrolimus, have been reported to be associated with dyslipidemia. The underlying mechanisms of calcineurin and tacrolimus in lipid [...] Read more.

Calcineurin is a calcium- and calmodulin-dependent serine/threonine protein phosphatase, and the target of immunosuppressive agent tacrolimus (TAC). The dysfunction of calcineurin, or clinical applications of tacrolimus, have been reported to be associated with dyslipidemia. The underlying mechanisms of calcineurin and tacrolimus in lipid metabolism are largely unknown. Here, we showed that mutations of tax-6 and cnb-1, which respectively encode the catalytic subunit and the regulatory subunit of calcineurin, together with tacrolimus treatment, consistently led to decreased fat accumulation and delayed growth in the nematode Caenorhabditis elegans. In contrast, disruption of the AMP-activated protein kinase (AMPK) encoded by aak-1 and aak-2 reversed the above effects in worms. Moreover, calcineurin deficiency and tacrolimus treatment consistently activated the transcriptional expression of the lipolytic gene atgl-1, encoding triglyceride lipase. Furthermore, RNAi knockdown of atgl-1 recovered the decreased fat accumulation in both calcineurin deficient and tacrolimus treated worms. Collectively, our results reveal that immunosuppressive agent tacrolimus and their target calcineurin may antagonize AMPK to regulate ATGL and lipolysis, thereby providing potential therapy for the application of immunosuppressive agents. Full article

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Open AccessArticle

Pamidronate-Conjugated Biodegradable Branched Copolyester Carriers: Synthesis and Characterization

by Ewa Oledzka^1,*

, Dagmara Pachowska¹, Katarzyna Orłowska¹, Joanna Kolmas²

, Agata Drobniewska³, Ramona Figat³ and Marcin Sobczak¹

¹ Department of Biomaterials Chemistry, Chair of Inorganic and Analytical Chemistry, Medical University of Warsaw, Faculty of Pharmacy with the Laboratory Medicine Division, Banacha 1, 02-097 Warsaw, Poland

² Department of Inorganic and Analytical Chemistry, Chair of Inorganic and Analytical Chemistry, Medical University of Warsaw, Faculty of Pharmacy with the Laboratory Medicine Division, Banacha 1, 02-097 Warsaw, Poland

³ Department of Environmental Health Science, Medical University of Warsaw, Faculty of Pharmacy with the Laboratory Medicine Division, Banacha 1, 02-097 Warsaw, Poland

Molecules 2017, 22(7), 1063; https://doi.org/10.3390/molecules22071063 - 26 Jun 2017

Cited by 7 | Viewed by 4823

Abstract

The need for development of comprehensive therapeutic systems, (e.g., polymer-apatite composites) as a bone substitute material has previously been highlighted in many scientific reports. The aim of this study was to develop a new multifunctional composite based on hydroxyapatite porous granules doped with [...] Read more.

The need for development of comprehensive therapeutic systems, (e.g., polymer-apatite composites) as a bone substitute material has previously been highlighted in many scientific reports. The aim of this study was to develop a new multifunctional composite based on hydroxyapatite porous granules doped with selenite ions (SeO₃²⁻) and a biodegradable branched copolymer-bisphosphonate conjugate as a promising bone substitute material for patients with bone tumours or bone metastasis. A series of biodegradable and branched copolymer matrices, adequate for delivery of bisphosphonate in the bone-deficient area were synthesized and physico-chemically and biologically (cyto- and genotoxicity assays) characterized. Branched copolymers were obtained using a hyperbranched bis-MPA polyester-16-hydroxyl initiator and Sn(Oct)₂, a (co)catalyst of the ring-opening polymerization (ROP) of l,l-lactide (LLA) and ε-caprolactone (CL). A new amide bond was formed between the hydroxyl end groups of the synthesized copolymer carriers and an amine group of pamidronate (PAM)—the drug inhibiting bone resorption and osteoclast activity in bone. The dependence of the physico-chemical properties of the copolymer matrices on the kinetic release of PAM from the synthesized branched copolymer conjugate-coated hydroxyapatite granules doped with selenite ions was observed. Moreover, the correlation of these results with the hydrolytic degradation data of the synthesized matrices was evidenced. Therefore, the developed composite porous hydroxyapatite doped with SeO₃²⁻ ions/biodegradable copolymer-PAM conjugate appears most attractive as a bone substitute material for cancer patients. Full article

(This article belongs to the Special Issue Biomedical Applications of Polylactide (PLA) and its Copolymers)

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Mechanism Exploration of Arylpiperazine Derivatives Targeting the 5-HT_2A Receptor by In Silico Methods

by Feng Lin^1,2, Feng Li³, Chao Wang², Jinghui Wang², Yinfeng Yang², Ling Yang⁴ and Yan Li^1,2,*

¹ Key Laboratory of Xinjiang Endemic Phytomedicine Resources, Pharmacy School, Shihezi University, Shihezi 832002, Xinjiang, China

² Key Laboratory of Industrial Ecology and Environmental Engineering (MOE), Faculty of Chemical, Environmental and Biological Science and Technology, Dalian University of Technology, Dalian 116024, Liaoning, China

³ Department of Civil Engineering, Henan Institute of Engineering, Zhengzhou 451191, Henan, China

⁴ Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China

Molecules 2017, 22(7), 1064; https://doi.org/10.3390/molecules22071064 - 26 Jun 2017

Cited by 18 | Viewed by 8040

Abstract

As a G-protein coupled receptor, the 5-hydroxytryptamine 2A (5-HT_2A) receptor is known for its critical role in the cognitive, behavioural and physiological functions, and thus is a primary molecular target to treat psychiatric diseases, including especially depression. With purpose to explore [...] Read more.

As a G-protein coupled receptor, the 5-hydroxytryptamine 2A (5-HT_2A) receptor is known for its critical role in the cognitive, behavioural and physiological functions, and thus is a primary molecular target to treat psychiatric diseases, including especially depression. With purpose to explore the structural traits affecting the inhibitory activity, currently a dataset of 109 arylpiperazine derivatives as promising 5-HT_2A antagonists was built, based on which the ligand-based three-dimensional quantitative structure-activity relationship (3D-QSAR) study by using both comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) approaches was carried out. The resultant optimal CoMSIA model displays proper validity and predictability with cross-validated correlation coefficient Q² = 0.587, non-cross-validated correlation coefficient R²_ncv = 0.900 and predicted correlation coefficient for the test set of compounds R²_pre = 0.897, respectively. Besides, molecular docking was also conducted to investigate the binding mode between these ligands and the active site of the 5-HT_2A receptor. Meanwhile, as a docking supplementary tool to study the antagonists’ conformation in the binding cavity, molecular dynamics (MD) simulation was also performed, providing further elucidation about the changes in the ligand-receptor complex. Lastly, some new molecules were also newly-designed based on the above results that are potential arylpiperazine antagonists of 5-HT_2A receptor. We hope that the present models and derived information may be of help for facilitating the optimization and design of novel potent antagonists as antidepressant drugs as well as exploring the interaction mechanism of 5-HT_2A antagonists. Full article

(This article belongs to the Special Issue Biomolecular Simulations)

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Open AccessArticle

UVA, UVB Light Doses and Harvesting Time Differentially Tailor Glucosinolate and Phenolic Profiles in Broccoli Sprouts

by Melissa Moreira-Rodríguez¹, Vimal Nair²

, Jorge Benavides¹, Luis Cisneros-Zevallos² and Daniel A. Jacobo-Velázquez^1,*

¹ Tecnológico de Monterrey, Escuela de Ingeniería y Ciencias, Centro de Biotecnología FEMSA, Av. Eugenio Garza Sada 2501 Sur, C.P. 64849 Monterrey, NL, Mexico

² Department of Horticultural Sciences, Texas A&M University, College Station, TX 77843-2133, USA

Molecules 2017, 22(7), 1065; https://doi.org/10.3390/molecules22071065 - 26 Jun 2017

Cited by 88 | Viewed by 8858

Abstract

Broccoli sprouts contain health-promoting glucosinolate and phenolic compounds that can be enhanced by applying ultraviolet light (UV). Here, the effect of UVA or UVB radiation on glucosinolate and phenolic profiles was assessed in broccoli sprouts. Sprouts were exposed for 120 min to low [...] Read more.

Broccoli sprouts contain health-promoting glucosinolate and phenolic compounds that can be enhanced by applying ultraviolet light (UV). Here, the effect of UVA or UVB radiation on glucosinolate and phenolic profiles was assessed in broccoli sprouts. Sprouts were exposed for 120 min to low intensity and high intensity UVA (UVA_L, UVA_H) or UVB (UVB_L, UVB_H) with UV intensity values of 3.16, 4.05, 2.28 and 3.34 W/m², respectively. Harvest occurred 2 or 24 h post-treatment; and methanol/water or ethanol/water (70%, v/v) extracts were prepared. Seven glucosinolates and 22 phenolics were identified. Ethanol extracts showed higher levels of certain glucosinolates such as glucoraphanin, whereas methanol extracts showed slight higher levels of phenolics. The highest glucosinolate accumulation occurred 24 h after UVB_H treatment, increasing 4-methoxy-glucobrassicin, glucobrassicin and glucoraphanin by ~170, 78 and 73%, respectively. Furthermore, UVA_L radiation and harvest 2 h afterwards accumulated gallic acid hexoside I (~14%), 4-O-caffeoylquinic acid (~42%), gallic acid derivative (~48%) and 1-sinapoyl-2,2-diferulolyl-gentiobiose (~61%). Increases in sinapoyl malate (~12%), gallotannic acid (~48%) and 5-sinapoyl-quinic acid (~121%) were observed with UVB_H Results indicate that UV-irradiated broccoli sprouts could be exploited as a functional food for fresh consumption or as a source of bioactive phytochemicals with potential industrial applications. Full article

(This article belongs to the Special Issue Recent Advances in Plant Phenolics)

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Open AccessEditorial

Special Issue: Chitin, Chitosan and Related Enzymes

by Massimiliano Fenice

Laboratory of Microbiology, and Laboratory of Applied Marine Microbiology (Conisma), University of Tuscia, I-01100 Viterbo, Italy

Molecules 2017, 22(7), 1066; https://doi.org/10.3390/molecules22071066 - 27 Jun 2017

Cited by 3 | Viewed by 3084

Abstract

Chitin and chitosan are very abundant natural polymers with distinctive properties, such as bioactivity, biocompatibility and biodegradability, that have inspired a number of basic and applied studies, mostly in biotechnology, medicine, food preservation and agriculture.[...] Full article

(This article belongs to the Special Issue Chitin, Chitosan and Related Enzymes)

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Open AccessArticle

Design, Synthesis and Evaluation of Hesperetin Derivatives as Potential Multifunctional Anti-Alzheimer Agents

by Bo Li^1,2,3, Ai-Ling Huang^1,2,3, Yi-Long Zhang^1,2,3, Zeng Li^1,2,3, Hai-Wen Ding^1,2,3, Cheng Huang^1,2,3, Xiao-Ming Meng^1,2,3 and Jun Li^1,2,3,*

¹ Anhui Province Key Laboratory of Major Autoimmune Diseases, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, 230000 Hefei, China

² The Key Laboratory of Anti-Inflammatory and Immune Medicines, Ministry of Education, 230000 Hefei, China

³ Institute for Liver Diseases, Anhui Medical University, 230000 Hefei, China

Molecules 2017, 22(7), 1067; https://doi.org/10.3390/molecules22071067 - 26 Jun 2017

Cited by 32 | Viewed by 5197

Abstract

In this study we designed and synthesized a series of new hesperetin derivatives on the basis of the structural characteristics of acetylcholinesterase (AChE) dual-site inhibitors. The activity of the novel derivatives was also evaluated. Results showed that the synthesized hesperetin derivatives displayed stronger [...] Read more.

In this study we designed and synthesized a series of new hesperetin derivatives on the basis of the structural characteristics of acetylcholinesterase (AChE) dual-site inhibitors. The activity of the novel derivatives was also evaluated. Results showed that the synthesized hesperetin derivatives displayed stronger inhibitory activity against AChE and higher selectivity than butyrylcholine esterase (BuChE) (selectivity index values from 68 to 305). The Lineweaver-Burk plot and molecular docking study showed that these compounds targeted both the peripheral anionic site (PAS) and catalytic active site (CAS) of AChE. The derivatives also showed a potent self-induced β-amyloid (Aβ) aggregation inhibition and a peroxyl radical absorbance activity. Moreover, compound 4f significantly protected PC12 neurons against H₂O₂-induced cell death at low concentrations. Cytotoxicity assay showed that the low concentration of the derivatives does not affect the viability of the SH-SY5Y neurons. Thus, these hesperetin derivatives are potential multifunctional agents for further development for the treatment of Alzheimer’s disease. Full article

(This article belongs to the Special Issue The Cholinesterases—Structure, Mechanism, Function and Drug Design: The 25th Anniversary of the Solution of the Crystal Structure of Acetylcholinesterase by Joel L. Sussman and Israel Silman)

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Open AccessArticle

High-Density Energetic Metal–Organic Frameworks Based on the 5,5′-Dinitro-2H,2′H-3,3′-bi-1,2,4-triazole

by Yalu Dong

, Panpan Peng, Baoping Hu, Hui Su, Shenghua Li^* and Siping Pang^*

School of Materials Science & Engineering, Beijing Institute of Technology, Beijing 100081, China

Molecules 2017, 22(7), 1068; https://doi.org/10.3390/molecules22071068 - 26 Jun 2017

Cited by 22 | Viewed by 5529

Abstract

High-energy metal–organic frameworks (MOFs) based on nitrogen-rich ligands are an emerging class of explosives, and density is one of the positive factors that can influence the performance of energetic materials. Thus, it is important to design and synthesize high-density energetic MOFs. In the [...] Read more.

High-energy metal–organic frameworks (MOFs) based on nitrogen-rich ligands are an emerging class of explosives, and density is one of the positive factors that can influence the performance of energetic materials. Thus, it is important to design and synthesize high-density energetic MOFs. In the present work, hydrothermal reactions of Cu(II) with the rigid polynitro heterocyclic ligands 5,5′-dinitro-2H,2′H-3,3′-bi-1,2,4-triazole (DNBT) and 5,5′-dinitro-3,3′-bis-1,2,4-triazole-1-diol (DNBTO) gave two high-density MOFs: [Cu(DNBT)(ATRZ)₃]_n (1) and [Cu(DNBTO)(ATRZ)₂(H₂O)₂]_n (2), where ATRZ represents 4,4′-azo-1,2,4-triazole. The structures were characterized by infrared spectroscopy, elemental analysis, ultraviolet-visible (UV) absorption spectroscopy and single-crystal X-ray diffraction. Their thermal stabilities were also determined by thermogravimetric/differential scanning calorimetry analysis (TG/DSC). The results revealed that complex 1 has a two-dimensional porous framework that possesses the most stable chair conformations (like cyclohexane), whereas complex 2 has a one-dimensional polymeric structure. Compared with previously reported MOFs based on copper ions, the complexes have higher density (ρ = 1.93 g cm⁻³ for complex 1 and ρ = 1.96 g cm⁻³ for complex 2) and high thermal stability (decomposition temperatures of 323 °C for complex 1 and 333.3 °C for complex 2), especially because of the introduction of an N–O bond in complex 2. We anticipate that these two complexes would be potential high-energy density materials. Full article

(This article belongs to the Section Organometallic Chemistry)

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Open AccessReview

Recent Advances in Substrate-Controlled Asymmetric Cyclization for Natural Product Synthesis

by Jeyun Jo^1,†, Seok-Ho Kim^2,†, Young Taek Han³, Jae-Hwan Kwak⁴ and Hwayoung Yun^1,*

¹ College of Pharmacy, Pusan National University, Busan 46241, Korea

² College of Pharmacy, Institute of Pharmaceutical Sciences, Cha University, Pocheon-si 11160, Korea

³ College of Pharmacy, Dankook University, Cheonan 31116, Korea

⁴ College of Pharmacy, Kyungsung University, Busan 48434, Korea

^† These authors contributed equally to this work.

Molecules 2017, 22(7), 1069; https://doi.org/10.3390/molecules22071069 - 26 Jun 2017

Cited by 3 | Viewed by 7131

Abstract

Asymmetric synthesis of naturally occurring diverse ring systems is an ongoing and challenging research topic. A large variety of remarkable reactions utilizing chiral substrates, auxiliaries, reagents, and catalysts have been intensively investigated. This review specifically describes recent advances in successful asymmetric cyclization reactions [...] Read more.

Asymmetric synthesis of naturally occurring diverse ring systems is an ongoing and challenging research topic. A large variety of remarkable reactions utilizing chiral substrates, auxiliaries, reagents, and catalysts have been intensively investigated. This review specifically describes recent advances in successful asymmetric cyclization reactions to generate cyclic architectures of various natural products in a substrate-controlled manner. Full article

(This article belongs to the Special Issue Asymmetric Synthesis 2017)

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Open AccessFeature PaperReview

Light-Assisted Advanced Oxidation Processes for the Elimination of Chemical and Microbiological Pollution of Wastewaters in Developed and Developing Countries

by Stefanos Giannakis^*

, Sami Rtimi

and Cesar Pulgarin^*

SB, ISIC, Group of Advanced Oxidation Processes (GPAO), École Polytechnique Fédérale de Lausanne (EPFL), Station 6, CH-1015 Lausanne, Switzerland

Molecules 2017, 22(7), 1070; https://doi.org/10.3390/molecules22071070 - 26 Jun 2017

Cited by 97 | Viewed by 8957

Abstract

In this work, the issue of hospital and urban wastewater treatment is studied in two different contexts, in Switzerland and in developing countries (Ivory Coast and Colombia). For this purpose, the treatment of municipal wastewater effluents is studied, simulating the developed countries’ context, [...] Read more.

In this work, the issue of hospital and urban wastewater treatment is studied in two different contexts, in Switzerland and in developing countries (Ivory Coast and Colombia). For this purpose, the treatment of municipal wastewater effluents is studied, simulating the developed countries’ context, while cheap and sustainable solutions are proposed for the developing countries, to form a barrier between effluents and receiving water bodies. In order to propose proper methods for each case, the characteristics of the matrices and the targets are described here in detail. In both contexts, the use of Advanced Oxidation Processes (AOPs) is implemented, focusing on UV-based and solar-supported ones, in the respective target areas. A list of emerging contaminants and bacteria are firstly studied to provide operational and engineering details on their removal by AOPs. Fundamental mechanistic insights are also provided on the degradation of the effluent wastewater organic matter. The use of viruses and yeasts as potential model pathogens is also accounted for, treated by the photo-Fenton process. In addition, two pharmaceutically active compound (PhAC) models of hospital and/or industrial origin are studied in wastewater and urine, treated by all accounted AOPs, as a proposed method to effectively control concentrated point-source pollution from hospital wastewaters. Their elimination was modeled and the degradation pathway was elucidated by the use of state-of-the-art analytical techniques. In conclusion, the use of light-supported AOPs was proven to be effective in degrading the respective target and further insights were provided by each application, which could facilitate their divulgation and potential application in the field. Full article

(This article belongs to the Special Issue Photon-involving Purification of Water and Air)

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Open AccessArticle

In Vitro Anti-Leishmanial Activity of Essential Oils Extracted from Vietnamese Plants

by Thanh Binh Le^1,2,*, Claire Beaufay¹

, Duc Trong Nghiem³

, Marie-Paule Mingeot-Leclercq⁴ and Joëlle Quetin-Leclercq^1,*

¹ GNOS Research Group, Louvain Drug Research Institue, Université Catholique de Louvain, Bruxelles 1200, Belgium

² Department of Pharmacognosy, Hanoi University of Pharmacy, 13-15 Le Thanh Tong, Hoan Kiem, Hanoi 100000, Vietnam

³ Department of Botany, Hanoi University of Pharmacy, 13-15 Le Thanh Tong, Hoan Kiem, Hanoi 100000, Vietnam

⁴ TFAR Research Group, Louvain Drug Research Institue, Université Catholique de Louvain, Bruxelles 1200, Belgium

Molecules 2017, 22(7), 1071; https://doi.org/10.3390/molecules22071071 - 27 Jun 2017

Cited by 38 | Viewed by 5268

Abstract

Leishmania mexicana is one of the pathogens causing cutaneous leishmaniasis which is associated with patient morbidity. In our researches for new safe and effective treatments, thirty-seven essential oils (EOs) extracted from Vietnamese plants were screened in vitro for the first time on Leishmania [...] Read more.

Leishmania mexicana is one of the pathogens causing cutaneous leishmaniasis which is associated with patient morbidity. In our researches for new safe and effective treatments, thirty-seven essential oils (EOs) extracted from Vietnamese plants were screened in vitro for the first time on Leishmania mexicana mexicana (Lmm) promastigotes at the maximum concentration of 50 nL/mL. Active EOs were also analyzed for cytotoxicity on mammalian cell lines (WI38, J774) and their selectivity indices (SI) were calculated. Their composition was determined by GC-MS and GC-FID. Our results indicated that EOs extracted from Cinnamomum cassia, Zingiber zerumbet, Elsholtzia ciliata and Amomum aromaticum, possessed a moderate anti-leishmanial activity, with IC₅₀ values of 2.92 ± 0.08, 3.34 ± 0.34, 8.49 ± 0.32 and 9.25 ± 0.64 nL/mL respectively. However, they also showed cytotoxicity with SI < 10. The most promising EO was extracted from Ocimum gratissimum, displaying an IC₅₀ of 4.85 ± 1.65 nL/mL and SI > 10. It contained 86.5% eugenol, which was demonstrated to be effective on Lmm with IC₅₀ of 2.57 ± 0.57 nL/mL and not toxic on mammalian cells, explaining the observed activity. Full article

(This article belongs to the Special Issue Essential Oils: Chemistry and Bioactivity)

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Open AccessArticle

Labradorins with Antibacterial Activity Produced by Pseudomonas sp.

by Anders Broberg^1,*, Joakim Bjerketorp¹, Pierre Andersson¹, Christer Sahlberg² and Jolanta J. Levenfors¹

¹ Department of Molecular Sciences, Uppsala BioCenter, the Swedish University of Agricultural Sciences, P.O. Box 7015, SE-750 07 Uppsala, Sweden

² Medivir AB, P.O. Box 1086, SE-141 22 Huddinge, Sweden

Molecules 2017, 22(7), 1072; https://doi.org/10.3390/molecules22071072 - 27 Jun 2017

Cited by 9 | Viewed by 8208

Abstract

The urgent need for new antibacterial drugs has led to renewed interest in microorganisms, which historically have been the main source of previously discovered antibiotics. The present study describes the discovery of two new antibacterial oxazolylindole type alkaloids, labradorins 5 (1) [...] Read more.

The urgent need for new antibacterial drugs has led to renewed interest in microorganisms, which historically have been the main source of previously discovered antibiotics. The present study describes the discovery of two new antibacterial oxazolylindole type alkaloids, labradorins 5 (1) and 6 (2), which were isolated and characterized from two isolates of Pseudomonas sp., along with four previously known tryptophane derived alkaloids. The structures of 1 and 2 were determined by NMR spectroscopy and MS, and confirmed by synthesis. During bioassay-guided isolation using several human bacterial pathogens, 1 and 2 displayed activity towards Staphylococcus aureus and Acinetobacter baumannii. The minimal inhibitory concentrations (MIC) of compounds 1 and 2 against S. aureus were 12 μg·mL⁻¹ and 50 μg·mL⁻¹, respectively, whereas the MICs against A. baumannii were >50 μg·mL⁻¹. The CC₅₀ values of compound 1 towards a liver cell line (HEP-G2) and a T-cell line (MT4) were 30 μg·mL⁻¹ and 20 μg·mL⁻¹, respectively, and for compound 2 were >100 μg·mL⁻¹ and 20 μg·mL⁻¹, respectively. Due to the limited potency of compounds 1 and 2, along with their toxicity, the compounds do not warrant further development towards new antibiotics. Full article

(This article belongs to the Collection Bioactive Compounds)

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Open AccessArticle

Nortriterpenoids from the Fruiting Bodies of the Mushroom Ganoderma resinaceum

by Xian-Qiang Chen¹, Ling-Xiao Chen¹, Jing Zhao^1,*, Yu-Ping Tang² and Shao-Ping Li^1,*

¹ State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau 999078, China

² Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Jiangsu Key Laboratory for High Technology Research of TCM Formulae, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China

Molecules 2017, 22(7), 1073; https://doi.org/10.3390/molecules22071073 - 28 Jun 2017

Cited by 22 | Viewed by 5191

Abstract

Ganoderma resinaceum is usually used as ethnomedicine for immune-regulation, hyperglycemia, and liver disease. To date, only a few chemical constituents have been reported from G. resinaceum. In this study, fifteen nortriterpenoids including six new nortriterpenoids (1–6) and [...] Read more.

Ganoderma resinaceum is usually used as ethnomedicine for immune-regulation, hyperglycemia, and liver disease. To date, only a few chemical constituents have been reported from G. resinaceum. In this study, fifteen nortriterpenoids including six new nortriterpenoids (1–6) and nine known analogs (7–15), were separated and purified from the fruiting bodies of G. resinaceum. New compounds were identified as lucidone I (1), lucidone J (2), lucidone K (3), lucidone I (4), ganosineniol B (5), and ganosineniol C (6), based on analysis of extensive spectroscopic data (high resolution mass spectrometry (HRMS), nuclear magnetic resonance (NMR), infrared (IR), and ultraviolet (UV)). The known compounds were assigned as lucidone A (7), lucidone B (8), lucidone H (9), lucidone E (10), lucidone F (11), lucidone D (12), lucidone C (13), ganoderense F (14), and ganosineniol A (15), by comparing their spectroscopic data with those reported in the literature. Compounds 3, 4, and 7–13 were examined for α-glucosidase inhibitory activity and display no significant activity, but the finding may support that the side chain of ganoderma triterpenoids played an important role in α-glucosidase inhibitory activity. Full article

(This article belongs to the Section Natural Products Chemistry)

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Open AccessReview

Self-Sterilizing Sputtered Films for Applications in Hospital Facilities

by Sami Rtimi^*, Stefanos Giannakis

and Cesar Pulgarin^*

Group of Advanced Oxidation Processes, Swiss Federal Institute of Technology, EPFL-SB-ISIC-GPAO, Station 6, CH-1015 Lausanne, Switzerland

Molecules 2017, 22(7), 1074; https://doi.org/10.3390/molecules22071074 - 28 Jun 2017

Cited by 22 | Viewed by 4389

Abstract

This review addresses the preparation of antibacterial 2D textile and thin polymer films and 3D surfaces like catheters for applications in hospital and health care facilities. The sputtering of films applying different levels of energy led to the deposition of metal/oxide/composite/films showing differentiated [...] Read more.

This review addresses the preparation of antibacterial 2D textile and thin polymer films and 3D surfaces like catheters for applications in hospital and health care facilities. The sputtering of films applying different levels of energy led to the deposition of metal/oxide/composite/films showing differentiated antibacterial kinetics and surface microstructure. The optimization of the film composition in regards to the antibacterial active component was carried out in each case to attain the fastest antibacterial kinetics, since this is essential when designing films avoiding biofilm formation (under light and in the dark). The antimicrobial performance of these sputtered films on Staphylococcus aureus (MRSA) and Escherichia coli (E. coli) were tested. A protecting effect of TiO₂ was found for the release of Cu by the TiO₂-Cu films compared to films sputtered by Cu only. The Cu-released during bacterial inactivation by TiO₂-Cu was observed to be much lower compared to the films sputtered only by Cu. The FeOx-TiO₂-PE films induced E. coli inactivation under solar or under visible light with a similar inactivation kinetics, confirming the predominant role of FeOx in these composite films. By up-to-date surface science techniques were used to characterize the surface properties of the sputtered films. A mechanism of bacteria inactivation is suggested for each particular film consistent with the experimental results found and compared with the literature. Full article

(This article belongs to the Special Issue Photon-involving Purification of Water and Air)

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Open AccessArticle

Cell-Free Production of Pentacyclic Triterpenoid Compound Betulinic Acid from Betulin by the Engineered Saccharomyces cerevisiae

by Jianan Wu, Yongwu Niu, Abdelmoneim Bakur

, Hao Li and Qihe Chen^*

Department of Food Science and Nutrition, Zhejiang University, Hangzhou 310058, China

Molecules 2017, 22(7), 1075; https://doi.org/10.3390/molecules22071075 - 27 Jun 2017

Cited by 13 | Viewed by 6104

Abstract

Betulinic acid is a product of plant secondary metabolism which has shown various bioactivities. Several CYP716A subfamily genes were recently characterized encoding multifunctional oxidases capable of C-28 oxidation. CYP716A12 was identified as betulin C-28 oxidase, capable of modifying betulin. This study aimed to [...] Read more.

Betulinic acid is a product of plant secondary metabolism which has shown various bioactivities. Several CYP716A subfamily genes were recently characterized encoding multifunctional oxidases capable of C-28 oxidation. CYP716A12 was identified as betulin C-28 oxidase, capable of modifying betulin. This study aimed to induce the transformation of betulin to betulinic acid by co-expressing enzymes CYP716A12 from Medicago truncatula and ATR1 from Arabidopsis thaliana in Saccharomyces cerevisiae. The microsome protein extracted from the transgenic yeast successfully catalyzed the transformation of betulin to betulinic acid. We also characterized the optimization of cell fragmentation, protein extraction method, and the conversion conditions. Response surface methodology was implemented, and the optimal yield of betulinic acid reached 18.70%. After optimization, the yield and the conversion rate of betulin were increased by 83.97% and 136.39%, respectively. These results may present insights and strategies for the sustainable production of betulinic acid in multifarious transgenic microbes. Full article

(This article belongs to the Collection Bioactive Compounds)

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Open AccessArticle

Ultrasonic Assisted-Reflux Synergistic Extraction of Camptothecin and Betulinic Acid from Camptotheca acuminata Decne. Fruits

by Chunying Li¹

, Yukun Zhang¹, Chunjian Zhao^1,2,*

, Yujiao Ni¹, Kaiting Wang¹, Jingjing Zhang¹ and Wenyan Zhao¹

¹ Key Laboratory of Forest Plant Ecology, Ministry of Education, Northeast Forestry University, Harbin 150040, China

² Collaborative Innovation Center for Development and Utilization of Forest Resources, Harbin 150040, China

Molecules 2017, 22(7), 1076; https://doi.org/10.3390/molecules22071076 - 27 Jun 2017

Cited by 18 | Viewed by 6161

Abstract

A novel and efficient ultrasonic assisted-reflux synergistic extraction (UARSE) method for extracting camptothecin (CPT) and betulinic acid (BA) from Camptotheca acuminata Decne. fruits has been developed in this study. The advantages of the ultrasonic and reflux extraction methods have been combined in the [...] Read more.

A novel and efficient ultrasonic assisted-reflux synergistic extraction (UARSE) method for extracting camptothecin (CPT) and betulinic acid (BA) from Camptotheca acuminata Decne. fruits has been developed in this study. The advantages of the ultrasonic and reflux extraction methods have been combined in the UARSE method and used to extract CPT and BA for the first time. The parameters influencing the efficiency of UARSE were optimized using the Box-Behnken design (BBD) to obtain the maximum extraction yield of CPT and BA. The optimal extraction conditions were as follows: 225 W for the ultrasonic power; 24 min for the extraction time; and 32 mL/g for the liquid–solid ratio. The extraction yields obtained by UARSE were 2.386 ± 0.112 mg/g for CPT and 17.192 ± 0.808 mg/g for BA, which were 1.43-fold and 1.33-fold, respectively, higher than by using heating reflux extraction (HRE) and ultrasonic-assisted extraction (UAE). In addition, the 24-min extraction time using UARSE was 80% and 60% less than those provided by HRE and UAE, respectively. Therefore, UARSE can be considered a rapid and efficient method for extracting CPT and BA from the fruits of C. acuminata Decne. Full article

(This article belongs to the Special Issue Green Extraction of Natural Product: Innovative Techniques, Alternative Solvents and Original Procedures)

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Open AccessArticle

Comparative Analysis of Saponins from Different Phytolaccaceae Species and Their Antiproliferative Activities

by Flora Didii Saleri^1,2,3, Guilin Chen^1,2, Xun Li^1,2 and Mingquan Guo^1,3,*

¹ Key Laboratory of Plant Germplasm Enhancement and Specialty Agriculture, Wuhan Botanical Garden, Chinese Academy of Sciences, Wuhan 430074, China

² University of Chinese Academy of Sciences, Beijing 100049, China

³ Sino-Africa Joint Research Center, Chinese Academy of Sciences, Wuhan 430074, China

Molecules 2017, 22(7), 1077; https://doi.org/10.3390/molecules22071077 - 29 Jun 2017

Cited by 18 | Viewed by 6526

Abstract

The quality and the efficacy of herbal medicine are of great concern especially with the increase in their global use. Medicinal plants of different species or collected from different geographical regions have shown variations in both their contents and pharmacological activities due to [...] Read more.

The quality and the efficacy of herbal medicine are of great concern especially with the increase in their global use. Medicinal plants of different species or collected from different geographical regions have shown variations in both their contents and pharmacological activities due to the differences in the environmental conditions of the collected sites. In this study, roots of Phytolacca acinosa found in different provinces in south China (Sichuan and Shandong) and a species of Phytolacca americana were investigated. To ensure a maximum yield of the major compounds, the extraction method and conditions were optimized. The preeminent method of extraction in this analysis was determined to be the ultrasound-assisted method with specific conditions as follows: ethanol-H₂O (1:1, v/v), with a solvent: sample ratio of 1:8, and extraction was performed 3 times, each for 30 min. Under these conditions, samples from the different regions varied both in quantity and quality via the LC-MS analysis. A total of 60 triterpenoid saponins were detected within the three samples, among which 22 were identified as common in the three samples. The amounts of these common triterpenoid saponin identified varied across the samples. Moreover, the analysis led to the detection of some novel compounds that have not yet been reported in this family, while other compounds differ in their fragmentation pathways compared to previous literature. To further divulge the correlations between the bioactivities in these three samples and the quantity and quality of their bioactive components, a cytotoxic analysis was thus carried out with two cancer cell lines, and SGC-7901 and Hep G2, which evidently showed remarkable differences in their anti-proliferative activities with respect to the IC₅₀ value. Samples of P. acinosa from Sichuan showed higher values in both cell lines (27.20 ± 1.60 and 25.59 ± 1.63 µg/mL) compared to those of Shandong and P. americana. For the first time, analysis and comparison of both interspecies and of different species in this family were carried out. This study will significantly contribute to the quality insurance of herbal medicine, especially in the Phytolaccaceae family. Full article

(This article belongs to the Special Issue Diversity of Terpenoids)

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Open AccessArticle

Effects on Rotational Dynamics of Azo and Hydrazodicarboxamide-Based Rotaxanes

by Adrian Saura-Sanmartin, Juan S. Martinez-Espin, Alberto Martinez-Cuezva^*

, Mateo Alajarin

and Jose Berna^*

Departamento de Química Orgánica, Facultad de Química, Regional Campus of International Excellence “Campus Mare Nostrum”, Universidad de Murcia, 30100 Murcia, Spain

Molecules 2017, 22(7), 1078; https://doi.org/10.3390/molecules22071078 - 28 Jun 2017

Cited by 12 | Viewed by 6178

Abstract

The synthesis of novel hydrogen-bonded [2]rotaxanes having two pyridine rings in the macrocycle and azo- and hydrazodicarboxamide-based templates decorated with four cyclohexyl groups is described. The different affinity of the binding sites for the benzylic amide macrocycle and the formation of programmed non-covalent [...] Read more.

The synthesis of novel hydrogen-bonded [2]rotaxanes having two pyridine rings in the macrocycle and azo- and hydrazodicarboxamide-based templates decorated with four cyclohexyl groups is described. The different affinity of the binding sites for the benzylic amide macrocycle and the formation of programmed non-covalent interactions between the interlocked components have an important effect on the dynamic behavior of these compounds. Having this in mind, the chemical interconversion between the azo and hydrazo forms of the [2]rotaxane was investigated to provide a chemically-driven interlocked system enable to switch its circumrotation rate as a function of the oxidation level of the binding site. Different structural modifications were carried out to further functionalize the nitrogen of the pyridine rings, including oxidation, alkylation or protonation reactions, affording interlocked azo-derivatives whose rotation dynamics were also analyzed. Full article

(This article belongs to the Special Issue ECSOC-20)

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Open AccessArticle

Spectroscopic Investigation of the Interaction of the Anticancer Drug Mitoxantrone with Sodium Taurodeoxycholate (NaTDC) and Sodium Taurocholate (NaTC) Bile Salts

by Mirela Enache^1,*, Ana Maria Toader¹, Victoria Neacsu¹, Gabriela Ionita¹ and Madalin I. Enache²

¹ Institute of Physical Chemistry Ilie Murgulescu, Romanian Academy, Splaiul Independentei 202, Bucharest 060021, Romania

² Institute of Biology, Romanian Academy, Splaiul Independentei 296, Bucharest 060031, Romania

Molecules 2017, 22(7), 1079; https://doi.org/10.3390/molecules22071079 - 28 Jun 2017

Cited by 14 | Viewed by 5642

Abstract

The focus of the present work was to investigate the interaction of the anticancer drug mitoxantrone with two bile salts, sodium taurodeoxycholate (NaTDC) and sodium taurocholate (NaTC). Ultraviolet-visible (UV-Vis) absorption and electron paramagnetic resonance (EPR) spectroscopy were used to quantify the interaction and [...] Read more.

The focus of the present work was to investigate the interaction of the anticancer drug mitoxantrone with two bile salts, sodium taurodeoxycholate (NaTDC) and sodium taurocholate (NaTC). Ultraviolet-visible (UV-Vis) absorption and electron paramagnetic resonance (EPR) spectroscopy were used to quantify the interaction and to obtain information on the location of mitoxantrone in bile salt micelles. The presence of submicellar concentrations of both bile salts induces mitoxantrone aggregation and the extent of drug aggregation in NaTDC is higher than in NaTC. For micellar bile salts concentrations, mitoxantrone monomers are entrapped in the micellar core. Binding constants, micelle/water partition coefficients and the corresponding thermodynamic parameters for binding and partitioning processes were estimated using the changes in monomer absorbance in the presence of bile salts. Binding interaction of mitoxantrone is stronger for NaTDC than NaTC micelles, whereas partitioning efficiency is higher for NaTC micelles for all investigated temperatures. Thermodynamic parameters indicate that both binding and partitioning processes are spontaneous and entropy controlled. The spectral behavior and thermodynamic parameters indicate distinct types of mitoxantrone interaction with NaTDC and NaTC micelles supported by the differences in nature and structure of bile salts micelles. Full article

(This article belongs to the Section Medicinal Chemistry)

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Open AccessArticle

Fabrication and Cytotoxicity of Gemcitabine-Functionalized Magnetite Nanoparticles

by Roxana Cristina Popescu^1,2, Ecaterina Andronescu², Bogdan Ștefan Vasile²

, Roxana Truşcă², Adina Boldeiu³

, Laurențiu Mogoantă⁴, George Dan Mogoșanu⁵, Mihaela Temelie¹, Mihai Radu¹

, Alexandru Mihai Grumezescu^2,*

and Diana Savu^1,*

¹ Department of Life and Environmental Physics, “Horia Hulubei” National Institute for Physics and Nuclear Engineering, 30 Reactorului Street, Măgurele 077125, Romania

² Department of Science and Engineering of Oxide Materials and Nanomaterials, Faculty of Applied Chemistry and Materials Science, University Politehnica of Bucharest, 1–7 Polizu Street, Bucharest 011061, Romania

³ Laboratory of Nanobiotechnology, National Institute for Research and Development in Microtechnologies, 12A Erou Iancu Nicolae Street, Bucharest 077190, Romania

⁴ Research Center for Microscopic Morphology and Immunology, University of Medicine and Pharmacy of Craiova, 2 Petru Rareș Street, Craiova 200349, Romania

⁵ Department of Pharmacognosy and Phytotherapy, Faculty of Pharmacy, University of Medicine and Pharmacy of Craiova, 2 Petru Rareș Street, Craiova 200349, Romania

Molecules 2017, 22(7), 1080; https://doi.org/10.3390/molecules22071080 - 28 Jun 2017

Cited by 39 | Viewed by 6629

Abstract

Nanotechnology has been successfully used for the fabrication of targeted anti-cancer drug carriers. This study aimed to obtain Fe₃O₄nanoparticles functionalized with Gemcitabine to improve the cytotoxic effects of the chemotherapeutic substance on cancer cells. The (un) functionalized magnetite nanoparticles [...] Read more.

Nanotechnology has been successfully used for the fabrication of targeted anti-cancer drug carriers. This study aimed to obtain Fe₃O₄nanoparticles functionalized with Gemcitabine to improve the cytotoxic effects of the chemotherapeutic substance on cancer cells. The (un) functionalized magnetite nanoparticles were synthesized using a modified co-precipitation method. The nanoconjugate characterization was performed by XRD, SEM, SAED and HRTEM; the functionalizing of magnetite with anti-tumor substances has been highlighted through TGA. The interaction with biologic media has been studied by means of stability and agglomeration tendency (using DLS and Zeta Potential); also, the release kinetics of the drug in culture media was evaluated. Cytotoxicity of free-Gemcitabine and the obtained nanoconjugate were evaluated on human BT 474 breast ductal carcinoma, HepG2 hepatocellular carcinoma and MG 63 osteosarcoma cells by MTS. In parallel, cellular morphology of these cells were examined through fluorescence microscopy and SEM. The localization of the nanoparticles related to the cells was studied using SEM, EDX and TEM. Hemolysis assay showed no damage of erythrocytes. Additionally, an in vivo biodistribution study was made for tracking where Fe₃O₄@Gemcitabine traveled in the body of mice. Our results showed that the transport of the drug improves the cytotoxic effects in comparison with the one produced by free Gemcitabine for the BT474 and HepG2 cells. The in vivo biodistribution test proved nanoparticle accumulation in the vital organs, with the exception of spleen, where black-brown deposits have been found. These results indicate that our Gemcitabine-functionalized nanoparticles are a promising targeted system for applications in cancer therapy. Full article

(This article belongs to the Special Issue Nanobiostructures: Commemorative Issue in Honor of Professor Serban Solacolu (1905-1980) - Founder of the Romanian School of Oxide Materials Science and Engineering)

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Open AccessArticle

Glycosylation of Recombinant Antigenic Proteins from Mycobacterium tuberculosis: In Silico Prediction of Protein Epitopes and Ex Vivo Biological Evaluation of New Semi-Synthetic Glycoconjugates

by Teodora Bavaro^1,†

, Sara Tengattini^1,†, Luciano Piubelli^2,3, Francesca Mangione⁴, Roberta Bernardini⁵, Vincenzina Monzillo^4,6, Sandra Calarota⁴, Piero Marone⁴, Massimo Amicosante⁵

, Loredano Pollegioni^2,3

, Caterina Temporini^1,*

and Marco Terreni¹

¹ Department of Drug Sciences, University of Pavia, via Taramelli 12, I-27100 Pavia, Italy

² Department of Biotechnology and Life Sciences, University of Insubria, via J.H. Dunant 3, I-21100 Varese, Italy

³ The Protein Factory, Interuniversity Centre Politecnico of Milano and University of Insubria, via Mancinelli 7, I-20131 Milano, Italy

⁴ Microbiology and Virology Unit, IRCCS San Matteo Hospital Foundation, viale Camillo Golgi 19, I-27100 Pavia, Italy

⁵ Department of Biomedicine and Prevention and Animal Technology Station, University of Rome “Tor Vergata”, via Montpellier 1, I-00133 Roma, Italy

⁶ Infection Disease Unit, Internal Medicine and Medical Therapy Department, University of Pavia, via Aselli 43/45, I-27100 Pavia, Italy

^† These authors equally contributed to the present paper.

Molecules 2017, 22(7), 1081; https://doi.org/10.3390/molecules22071081 - 29 Jun 2017

Cited by 17 | Viewed by 6030

Abstract

Tuberculosis is still one of the most deadly infectious diseases worldwide, and the use of conjugated antigens, obtained by combining antigenic oligosaccharides, such as the lipoarabinomannane (LAM), with antigenic proteins from Mycobacterium tuberculosis (MTB), has been proposed as a new strategy for developing [...] Read more.

Tuberculosis is still one of the most deadly infectious diseases worldwide, and the use of conjugated antigens, obtained by combining antigenic oligosaccharides, such as the lipoarabinomannane (LAM), with antigenic proteins from Mycobacterium tuberculosis (MTB), has been proposed as a new strategy for developing efficient vaccines. In this work, we investigated the effect of the chemical glycosylation on two recombinant MTB proteins produced in E. coli with an additional seven-amino acid tag (recombinant Ag85B and TB10.4). Different semi-synthetic glycoconjugated derivatives were prepared, starting from mannose and two disaccharide analogs. The glycans were activated at the anomeric position with a thiocyanomethyl group, as required for protein glycosylation by selective reaction with lysines. The glycosylation sites and the ex vivo evaluation of the immunogenic activity of the different neo-glycoproteins were investigated. Glycosylation does not modify the immunological activity of the TB10.4 protein. Similarly, Ag85B maintains its B-cell activity after glycosylation while showing a significant reduction in the T-cell response. The results were correlated with the putative B- and T-cell epitopes, predicted using a combination of in silico systems. In the recombinant TB10.4, the unique lysine is not included in any T-cell epitope. Lys30 of Ag85B, identified as the main glycosylation site, proved to be the most important site involved in the formation of T-cell epitopes, reasonably explaining why its glycosylation strongly influenced the T-cell activity. Furthermore, additional lysines included in different epitopes (Lys103, -123 and -282) are also glycosylated. In contrast, B-cell epitopic lysines of Ag85B were found to be poorly glycosylated and, thus, the antibody interaction of Ag85B was only marginally affected after coupling with mono- or disaccharides. Full article

(This article belongs to the Special Issue Synthesis and Biological Applications of Glycoconjugates)

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Open AccessReview

Olive Polyphenols and the Metabolic Syndrome

by Bandhita Saibandith, Jeremy P. E. Spencer, Ian R. Rowland and Daniel M. Commane^*

Hugh Sinclair Unit of Human Nutrition, Department of Food and Nutritional Sciences, School of Chemistry Food and Pharmacy, University of Reading, Whiteknights, Reading RG6 6AH, UK

Molecules 2017, 22(7), 1082; https://doi.org/10.3390/molecules22071082 - 29 Jun 2017

Cited by 76 | Viewed by 16024

Abstract

Here, the effects of consuming polyphenol-rich olive products, including olive leaves, their crude extract, and extra virgin olive oil, on aspects of the metabolic syndrome are reviewed. We have sought to summarize the available scientific evidence from dietary intervention trials demonstrating a role [...] Read more.

Here, the effects of consuming polyphenol-rich olive products, including olive leaves, their crude extract, and extra virgin olive oil, on aspects of the metabolic syndrome are reviewed. We have sought to summarize the available scientific evidence from dietary intervention trials demonstrating a role for these phytochemicals in ameliorating aberrant glucose metabolism, high blood pressure and elevated blood lipids, and we discuss the potential mechanisms underpinning these observations. Searches for relevant literature published in English were conducted via PubMed and Science Direct. Based on published dietary intervention studies, there is convincing evidence to show that olive polyphenols, independently of olive lipids, reduce risk factors for metabolic syndrome, in particular by improving blood sugar and blood pressure control, and in reducing low density lipoprotein oxidation. There is more limited evidence to suggest that the consumption of olive polyphenols or related products can reduce body weight and visceral fat or impede weight gain, and similarly there are some limited data suggesting improved lipid profiles. There is some mechanistic data to support observations made in human volunteers, but further work is needed in this area. The consumption of olive polyphenols within the context of a healthy pattern of food intake may, in part, explain the reduced risk of metabolic disease associated with adherence to the Mediterranean diet. Full article

(This article belongs to the Special Issue Bioactive Compounds for Metabolic Syndrome and Type 2 Diabetes)

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Open AccessFeature PaperArticle

The C5 Variant of the Butyrylcholinesterase Tetramer Includes a Noncovalently Bound 60 kDa Lamellipodin Fragment

by Lawrence M. Schopfer¹, Hervé Delacour², Patrick Masson^1,3

, Jacqueline Leroy⁴, Eric Krejci⁴

and Oksana Lockridge^1,*

¹ Eppley Institute, University of Nebraska Medical Center, Omaha, NE 68198-5950, USA

² Hôpital d’Instruction des Armées Bégin-Département des Laboratoires, 69, Avenue de Paris, 94 163 Saint Mandé, France

³ Neuropharmacology Laboratory, Kazan Federal University, 420000 Kazan, Russia

⁴ CNRS Université Paris Descartes Cognition Action Group UMR 8257, 75006 Paris, France

Molecules 2017, 22(7), 1083; https://doi.org/10.3390/molecules22071083 - 29 Jun 2017

Cited by 15 | Viewed by 5822

Abstract

Humans with the C5 genetic variant of butyrylcholinesterase (BChE) have 30–200% higher plasma BChE activity, low body weight, and shorter duration of action of the muscle relaxant succinylcholine. The C5 variant has an extra, slow-moving band of BChE activity on native polyacrylamide gel [...] Read more.

Humans with the C5 genetic variant of butyrylcholinesterase (BChE) have 30–200% higher plasma BChE activity, low body weight, and shorter duration of action of the muscle relaxant succinylcholine. The C5 variant has an extra, slow-moving band of BChE activity on native polyacrylamide gel electrophoresis. This band is about 60 kDa larger than wild-type BChE. Umbilical cord BChE in 100% of newborn babies has a C5-like band. Our goal was to identify the unknown, 60 kDa protein in C5. Both wild-type and C5 BChE are under the genetic control of two independent loci, the BCHE gene on Chr 3q26.1 and the RAPH1 (lamellipodin) gene on Chr 2q33. Wild-type BChE tetramers are assembled around a 3 kDa polyproline peptide from lamellipodin. Western blot of boiled C5 and cord BChE showed a positive response with an antibody to the C-terminus of lamellipodin. The C-terminal exon of lamellipodin is about 60 kDa including an N-terminal polyproline. We propose that the unknown protein in C5 and cord BChE is encoded by the last exon of the RAPH1 gene. In 90% of the population, the 60 kDa fragment is shortened to 3 kDa during maturation to adulthood, leaving only 10% of adults with C5 BChE. Full article

(This article belongs to the Special Issue The Cholinesterases—Structure, Mechanism, Function and Drug Design: The 25th Anniversary of the Solution of the Crystal Structure of Acetylcholinesterase by Joel L. Sussman and Israel Silman)

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Open AccessArticle

Water-soluble Manganese and Iron Mesotetrakis(carboxyl)porphyrin: DNA Binding, Oxidative Cleavage, and Cytotoxic Activities

by Lei Shi^1,2,*, Yi-Yu Jiang³, Tao Jiang¹, Wei Yin^1,2, Jian-Ping Yang^1,2, Man-Li Cao^1,2, Yu-Qi Fang¹ and Hai-Yang Liu^3,*

¹ Department of Chemistry, Guangdong University of Education, Guangzhou 510303, China

² Engineering Technology Development Center of Advanced Materials & Energy Saving and Emission Reduction in Guangdong Colleges and Universities, Guangzhou 510303, China

³ Department of Chemistry, South China University of Technology, Guangzhou 510641, China

Molecules 2017, 22(7), 1084; https://doi.org/10.3390/molecules22071084 - 29 Jun 2017

Cited by 24 | Viewed by 6188

Abstract

Two new water-soluble metal carboxyl porphyrins, manganese (III) meso-tetrakis (carboxyl) porphyrin and iron (III) meso-tetrakis (carboxyl) porphyrin, were synthesized and characterized. Their interactions with ct-DNA were investigated by UV-Vis titration, fluorescence spectra, viscosity measurement and CD spectra. The results showed they [...] Read more.

Two new water-soluble metal carboxyl porphyrins, manganese (III) meso-tetrakis (carboxyl) porphyrin and iron (III) meso-tetrakis (carboxyl) porphyrin, were synthesized and characterized. Their interactions with ct-DNA were investigated by UV-Vis titration, fluorescence spectra, viscosity measurement and CD spectra. The results showed they can strongly bind to ct-DNA via outside binding mode. Electrophoresis experiments revealed that both complexes can cleave pBR322 DNA efficiently in the presence of hydrogen peroxide, albeit 2-Mn exhibited a little higher efficiency. The inhibitor tests suggest the oxidative DNA cleavage by these two complexes may involve hydroxyl radical active intermediates. Notably, 2-Mn exhibited considerable photocytotoxicity against Hep G2 cell via triggering a significant generation of ROS and causing disruption of MMP after irradiation. Full article

(This article belongs to the Section Bioorganic Chemistry)

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Open AccessArticle

An All-Nanocrystal Biosensing System for In Vitro Detection of STAT3 Oligonucleotides

by Wei Kong^1,2, Chau Fan Lam¹ and Feng Wang^1,2,*

¹ Department of Physics and Materials Science, City University of Hong Kong, 83 Tat Chee Avenue, Hong Kong, China

² City University of Hong Kong Shenzhen Research Institute, Shenzhen 518057, China

Molecules 2017, 22(7), 1085; https://doi.org/10.3390/molecules22071085 - 29 Jun 2017

Cited by 1 | Viewed by 4549

Abstract

Lanthanide-doped nanocrystals have shown great promise in bio-detection due to their outstanding luminescent properties, including large Stokes shift and sharp emission bands. Herein, we describe an in vitro detection of STAT3 by using an all-nanocrystal biosensing system that takes advantage of inter-particle energy [...] Read more.

Lanthanide-doped nanocrystals have shown great promise in bio-detection due to their outstanding luminescent properties, including large Stokes shift and sharp emission bands. Herein, we describe an in vitro detection of STAT3 by using an all-nanocrystal biosensing system that takes advantage of inter-particle energy transfer between two types of lanthanide-doped nanocrystals. We investigate the effect of nanocrystal size on the sensing performance and find that smaller nanocrystals offer a lower detection limit and larger dynamic range. As STAT3 is identified as an oncogene aberrantly activated and expressed in malignant transformation and tumorigenesis, our study thus holds promise for cancer diagnosis and therapy. Full article

(This article belongs to the Special Issue Nanocrystals: Synthesis, Characterization and Applications)

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Open AccessCommunication

A Novel Synthesis of the Efficient Anti-Coccidial Drug Halofuginone Hydrobromide

by Junren Zhang^1,2,†

, Qizheng Yao^3,† and Zuliang Liu^1,*

¹ School of Chemical Engineering, Nanjing University of Science and Technology, Nanjing 210094, China

² Laboratory of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China

³ School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China

^† These authors contributed equally to this work.

Molecules 2017, 22(7), 1086; https://doi.org/10.3390/molecules22071086 - 30 Jun 2017

Cited by 11 | Viewed by 6265

Abstract

Background: Halofuginone hydrobromide (1) is recognized as an effective drug against several species of Eimeria (E.) in poultry. In this paper, we describe a convenient and low cost preparation method for the compound, as well as primary validation of its [...] Read more.

Background: Halofuginone hydrobromide (1) is recognized as an effective drug against several species of Eimeria (E.) in poultry. In this paper, we describe a convenient and low cost preparation method for the compound, as well as primary validation of its activity. Methods: First, 7-bromo-6-chloroquinazolin-4(3H)-one (2) was prepared from m-chlorotoluene by a conventional process, and then chloroacetone was creatively introduced in two steps. Finally, halofuginone hydrobromide (1) was obtained from 7-bromo-6-chloro-3-(3-cholroacetonyl) quinazolin-4(3H)-one (4) by a four-step reaction sequence including condensation, cyclization, deprotection and isomerization. The structures of the relative intermediates and target compound were characterized by melting point, IR, MS and ¹H-NMR. Besides, the protective effect of compound 1-supplemented chicken diet at doses of 6, 3 and 1.5 mg per 1 kg were evaluated on chickens infected with E. tenella, by reduction in mortality, weight loss, fecal oocyst excretion and gut pathology, respectively. Results: Halofuginone hydrobromide (1) was prepared successfully by and improved and innovative method based on traditional research. Moreover, the synthesized halofuginone hydrobromide significantly exhibited an anti-coccidial property. Conclusions: The fruitful work described in this Communication has resulted in halofuginone hydrobromide, which has a good pharmaceutical development prospects, becoming more available for large-scale production. Full article

(This article belongs to the Section Medicinal Chemistry)

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Open AccessArticle

Synthesis and In Vitro Anticancer Activity of Novel Dehydroabietic Acid-Based Acylhydrazones

by Fang-Yao Li^1,2, Xiu Wang², Wen-Gui Duan^1,* and Gui-Shan Lin¹

¹ School of Chemistry and Chemical Engineering, Guangxi University, Nanning 530004, Guangxi, China

² College of Pharmacy, Guilin Medical University, Guilin 541004, Guangxi, China

Molecules 2017, 22(7), 1087; https://doi.org/10.3390/molecules22071087 - 29 Jun 2017

Cited by 33 | Viewed by 4406

Abstract

In order to develop novel chemotherapeutic agents with potent anticancer activities, a series of dehydroabietic acid (DHA) derivatives bearing an acylhydrazone moiety were designed and synthesized by the condensation between dehydroabietic acylhydrazide (3) and a variety of substituted arylaldehydes. The inhibitory activities of [...] Read more.

In order to develop novel chemotherapeutic agents with potent anticancer activities, a series of dehydroabietic acid (DHA) derivatives bearing an acylhydrazone moiety were designed and synthesized by the condensation between dehydroabietic acylhydrazide (3) and a variety of substituted arylaldehydes. The inhibitory activities of these compounds against CNE-2 (nasopharynx), HepG2 (liver), HeLa (epithelial cervical), and BEL-7402 (liver) human carcinoma cell lines were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay in vitro. The screening results revealed that many of the compounds showed moderate to high levels of anticancer activities against the tested cancer cell lines and some displayed similar potent inhibitory activities to the commercial anticancer drug cisplatin, while they exhibited lower cytotoxicity against normal human liver cell (HL-7702). Particularly, compound 4w, N’-(3,5-difluorobenzylidene)-2-(dehydroabietyloxy)acetohydrazide, with an IC₅₀(50% inhibitory concentration) value of 2.21 μM against HeLa cell, was about 17-fold more active than that of the parent compound, and showed remarkable cytotoxicity with an IC₅₀ value of 14.46 μM against BEL-7402 cell. These results provide an encouraging framework that could lead to the development of potent novel anticancer agents. Full article

(This article belongs to the Section Medicinal Chemistry)

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Open AccessArticle

New Heterofunctional Supports Based on Glutaraldehyde-Activation: A Tool for Enzyme Immobilization at Neutral pH

by Ricardo Rodrigues de Melo^1,2,3,†, Robson Carlos Alnoch^1,4,†

, Adriana Ferreira Lopes Vilela^1,5, Emanuel Maltempi de Souza⁴, Nadia Krieger⁶, Roberto Ruller²

, Hélia Harumi Sato³ and Cesar Mateo^1,*

¹ Departamento de Biocatálisis, Instituto de Catálisis y Petroleoquímica (CSIC), Marie Curie 2. Cantoblanco, Campus UAM, 28049 Madrid, Spain

² Laboratório Nacional de Ciência e Tecnologia do Bioetanol (CTBE), Centro Nacional de Pesquisa em Energia e Materiais (CNPEM), Cx. P. 6192, 13083-970 Campinas, São Paulo, Brazil

³ Departamento de Ciência de Alimentos, Faculdade de Engenharia de Alimentos (FEA), Universidade Estadual de Campinas (UNICAMP), 13083-862 Campinas, São Paulo, Brazil

⁴ Departamento de Bioquímica e Biologia Molecular, Universidade Federal do Paraná, Cx. P. 19081 Centro Politécnico, 81531-980 Curitiba, Paraná, Brazil

⁵ Departamento de Química, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, 14040-901 Ribeirão Preto, São Paulo, Brazil

⁶ Departamento de Química, Universidade Federal do Paraná, Cx. P. 19081 Centro Politécnico, 81531-980 Curitiba, Paraná, Brazil

^† Author contributions: These authors contributed equally to this work.

Molecules 2017, 22(7), 1088; https://doi.org/10.3390/molecules22071088 - 29 Jun 2017

Cited by 47 | Viewed by 7567

Abstract

Immobilization is an exciting alternative to improve the stability of enzymatic processes. However, part of the applied covalent strategies for immobilization uses specific conditions, generally alkaline pH, where some enzymes are not stable. Here, a new generation of heterofunctional supports with application at [...] Read more.

Immobilization is an exciting alternative to improve the stability of enzymatic processes. However, part of the applied covalent strategies for immobilization uses specific conditions, generally alkaline pH, where some enzymes are not stable. Here, a new generation of heterofunctional supports with application at neutral pH conditions was proposed. New supports were developed with different bifunctional groups (i.e., hydrophobic or carboxylic/metal) capable of adsorbing biocatalysts at different regions (hydrophobic or histidine richest place), together with a glutaraldehyde group that promotes an irreversible immobilization at neutral conditions. To verify these supports, a multi-protein model system (E. coli extract) and four enzymes (Candida rugosa lipase, metagenomic lipase, β-galactosidase and β-glucosidase) were used. The immobilization mechanism was tested and indicated that moderate ionic strength should be applied to avoid possible unspecific adsorption. The use of different supports allowed the immobilization of most of the proteins contained in a crude protein extract. In addition, different supports yielded catalysts of the tested enzymes with different catalytic properties. At neutral pH, the new supports were able to adsorb and covalently immobilize the four enzymes tested with different recovered activity values. Notably, the use of these supports proved to be an efficient alternative tool for enzyme immobilization at neutral pH. Full article

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Open AccessArticle

Characterization of Polyelectrolyte Complex Formation Between Anionic and Cationic Poly(amino acids) and Their Potential Applications in pH-Dependent Drug Delivery

by Zoë Folchman-Wagner¹

, Jennica Zaro²

and Wei-Chiang Shen^1,*

¹ Department of Pharmaceutical Sciences, University of Southern California School of Pharmacy, 1985 Zonal Avenue, Los Angeles, CA 90089, USA

² Department of Pharmaceutical Sciences, West Coast University School of Pharmacy, 590 Vermont Ave, Los Angeles, CA 90004, USA

Molecules 2017, 22(7), 1089; https://doi.org/10.3390/molecules22071089 - 30 Jun 2017

Cited by 22 | Viewed by 5527

Abstract

Polyelectrolyte complexes (PECs) are self-assembling nano-sized constructs that offer several advantages over traditional nanoparticle carriers including controllable size, biodegradability, biocompatibility, and lack of toxicity, making them particularly appealing as tools for drug delivery. Here, we discuss potential application of PECs for drug delivery [...] Read more.

Polyelectrolyte complexes (PECs) are self-assembling nano-sized constructs that offer several advantages over traditional nanoparticle carriers including controllable size, biodegradability, biocompatibility, and lack of toxicity, making them particularly appealing as tools for drug delivery. Here, we discuss potential application of PECs for drug delivery to the slightly acidic tumor microenvironment, a pH in the range of 6.5–7.0. Poly(l-glutamic acid) (E_n), poly(l-lysine) (K_n), and a copolymer composed of histidine-glutamic acid repeats ((HE)_n) were studied for their ability to form PECs, which were analyzed for size, polydispersity, and pH sensitivity. PECs showed concentration dependent size variation at residue lengths of E₅₁/K₅₅ and E₁₃₅/K₁₂₇, however, no complexes were observed when E₂₂ or K₂₁ were used, even in combination with the longer chains. (HE)₂₀/K₅₅ PECs could encapsulate daunomycin, were stable from pH 7.4–6.5, and dissociated completely between pH 6.5–6.0. Conversely, the E_51-dauno/K₅₅ PEC dissociated between pH 4.0 and 3.0. These values for pH-dependent particle dissociation are consistent with the pK_a’s of the ionizable groups in each formulation and indicate that the specific pH-sensitivity of (HE)_20-dauno/K₅₅ PECs is mediated by incorporation of histidine. This response within a pH range that is physiologically relevant to the acidic tumors suggests a potential application of these PECs in pH-dependent drug delivery. Full article

(This article belongs to the Special Issue Peptide-Based Drugs and Drug Delivery Systems)

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Open AccessErratum

Erratum: Ksiksi, T., et al. Antioxidant, Lipoxygenase and Histone Deacetylase Inhibitory Activities of Acridocarpus orientalis from Al Ain and Oman. Molecules 2012, 17, 12521–12532.

by Molecules Editorial Office

MDPI AG, St. Alban-Anlage 66, 4052 Basel, Switzerland

Molecules 2017, 22(7), 1090; https://doi.org/10.3390/molecules22071090 - 30 Jun 2017

Viewed by 2119

Abstract

The Molecules Editorial Office wishes to make the following erratum to this paper [1]. [...]
Full article

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Open AccessArticle

Polyurethane Foams for Thermal Insulation Uses Produced from Castor Oil and Crude Glycerol Biopolyols

by Camila S. Carriço¹, Thaís Fraga¹, Vagner E. Carvalho² and Vânya M. D. Pasa^1,*

¹ Laboratório de Produtos da Biomassa, Departamento de Química, Universidade Federal de Minas Gerais, Av. Antonio Carlos, 6627, 31270-901 Belo Horizonte, Minas Gerais, Brazil

² Laboratório de Física de Superfícies, Departamento de Física, Universidade Federal de Minas Gerais, Av. Antonio Carlos, 6627, 31270-901 Belo Horizonte, Minas Gerais, Brazil

Molecules 2017, 22(7), 1091; https://doi.org/10.3390/molecules22071091 - 2 Jul 2017

Cited by 52 | Viewed by 10342

Abstract

Rigid polyurethane foams were synthesized using a renewable polyol from the simple physical mixture of castor oil and crude glycerol. The effect of the catalyst (DBTDL) content and blowing agents in the foams’ properties were evaluated. The use of physical blowing agents (cyclopentane [...] Read more.

Rigid polyurethane foams were synthesized using a renewable polyol from the simple physical mixture of castor oil and crude glycerol. The effect of the catalyst (DBTDL) content and blowing agents in the foams’ properties were evaluated. The use of physical blowing agents (cyclopentane and n-pentane) allowed foams with smaller cells to be obtained in comparison with the foams produced with a chemical blowing agent (water). The increase of the water content caused a decrease in density, thermal conductivity, compressive strength, and Young’s modulus, which indicates that the increment of CO₂ production contributes to the formation of larger cells. Higher amounts of catalyst in the foam formulations caused a slight density decrease and a small increase of thermal conductivity, compressive strength, and Young’s modulus values. These green foams presented properties that indicate a great potential to be used as thermal insulation: density (23–41 kg·m⁻³), thermal conductivity (0.0128–0.0207 W·m⁻¹·K⁻¹), compressive strength (45–188 kPa), and Young’s modulus (3–28 kPa). These biofoams are also environmentally friendly polymers and can aggregate revenue to the biodiesel industry, contributing to a reduction in fuel prices. Full article

(This article belongs to the Special Issue Natural Polymers and Biopolymers)

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Open AccessArticle

In Vitro Effect of 8-Prenylnaringenin and Naringenin on Fibroblasts and Glioblastoma Cells-Cellular Accumulation and Cytotoxicity

by Monika Stompor^1,2,*

, Łukasz Uram³ and Rafał Podgórski^1,2

¹ Centre for Innovative Research in Medical and Natural Sciences, Faculty of Medicine, University of Rzeszów, Warzywna 1a, 35-310 Rzeszów, Poland

² Department of Biochemistry, Faculty of Medicine, University of Rzeszów, Warzywna 1a, 35-310 Rzeszów, Poland

³ Faculty of Chemistry, Rzeszów University of Technology, 6 Powstańców Warszawy Ave, 35-959 Rzeszów, Poland

Molecules 2017, 22(7), 1092; https://doi.org/10.3390/molecules22071092 - 30 Jun 2017

Cited by 49 | Viewed by 6673

Abstract

Gliomas are one of the most aggressive and treatment-resistant types of human brain cancer. Identification and evaluation of anticancer properties of compounds found in plants, such as naringenin (N) and 8-prenylnaringenin (8PN), are among the most promising applications in glioma therapy. The prenyl [...] Read more.

Gliomas are one of the most aggressive and treatment-resistant types of human brain cancer. Identification and evaluation of anticancer properties of compounds found in plants, such as naringenin (N) and 8-prenylnaringenin (8PN), are among the most promising applications in glioma therapy. The prenyl group seems to be crucial to the anticancer activity of flavones, since it may lead to enhanced cell membrane targeting and thus increased intracellular activity. It should be noted that 8PN content in hop cones is 10 to 100 times lower compared to other flavonoids, such as xanthohumol. In the study presented, we used a simple method for the synthesis of 8PN from isoxanthohumol—O-demethylation, with a high yield of 97%. Cellular accumulation and cytotoxicity of naringenin and 8-prenylnaringenin in normal (BJ) and cancer cells (U-118 MG) was also examined. Obtained data indicated that 8-prenylnaringenin exhibited higher cytotoxicity against used cell lines than naringenin, and the effect of both flavones was stronger in U-118 MG cells than in normal fibroblasts. The anticancer properties of 8PN correlated with its significantly greater (37%) accumulation in glioblastoma cells than in normal fibroblasts. Additionally, naringenin demonstrated higher selectivity for glioblastoma cells, as it was over six times more toxic for cancer than normal cells. Our results provide evidence that examined prenylated and non-prenylated flavanones have different biological activities against normal and cancer cell lines, and this property may be useful in designing new anticancer drugs for glioblastoma therapy. Full article

(This article belongs to the Section Natural Products Chemistry)

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Open AccessArticle

Metal Atom Effect on the Photophysical Properties of Mg(II), Zn(II), Cd(II), and Pd(II) Tetraphenylporphyrin Complexes Proposed as Possible Drugs in Photodynamic Therapy

by Bruna Clara De Simone, Gloria Mazzone

, Nino Russo^*, Emilia Sicilia and Marirosa Toscano

Dipartimento di Chimica e Tecnologie Chimiche, Università della Calabria, I-87036 Arcavacata di Rende, Italy

Molecules 2017, 22(7), 1093; https://doi.org/10.3390/molecules22071093 - 30 Jun 2017

Cited by 44 | Viewed by 6050

Abstract

The effects of Mg, Zn, Cd, and Pd dications on the photophysical properties of the tetraphenylporphyrin ligand have been explored, considering the corresponding complexes and by using the density functional theory and its time-dependent extension. Results show that absorption wavelengths do not change [...] Read more.

The effects of Mg, Zn, Cd, and Pd dications on the photophysical properties of the tetraphenylporphyrin ligand have been explored, considering the corresponding complexes and by using the density functional theory and its time-dependent extension. Results show that absorption wavelengths do not change significantly when the metal ion changes contrary to what happens to the singlet–triplet energy gaps (ΔE_S−T) and the spin-orbit matrix elements ΨSnHsoΨTm. The most probable intersystem spin crossing (ISC) pathways for the population of the lowest triplet states have been explored. Our findings can contribute to rationalize the available experimental data and promote the potential therapeutic use of these compounds as photosensitizers in photodynamic therapy (PDT). Full article

(This article belongs to the Special Issue Frontiers in Computational Chemistry for Drug Discovery)

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Open AccessArticle

Molecular Docking and Anticonvulsant Activity of Newly Synthesized Quinazoline Derivatives

by Hatem A. Abuelizz¹

, Rabab El Dib^2,3, Mohamed Marzouk^4,5, El-Hassane Anouar⁴

, Yousreya A. Maklad⁶, Hanan N. Attia⁶

and Rashad Al-Salahi^1,*

¹ Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia

² Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh 11495, Saudi Arabia

³ Department of Pharmacognosy, Faculty of Pharmacy, Helwan University, Cairo 11795, Egypt

⁴ Department of Chemistry, College of Science and Humanities, Prince Sattam bin Abdulaziz University, P.O. Box 83, Alkharj 11942, Saudi Arabia

⁵ Chemistry of Natural Products Group, Center of Excellence for Advanced Sciences, National Research Centre, Dokki, Cairo 12622, Egypt

⁶ Medicinal and Pharmaceutical Chemistry Department (Pharmacology group), Pharmaceutical and Drug Industries Research Division, National Research Centre, Dokki, Giza 12622, Egypt

Molecules 2017, 22(7), 1094; https://doi.org/10.3390/molecules22071094 - 30 Jun 2017

Cited by 62 | Viewed by 11078

Abstract

A new series of quinazoline-4(3H)-ones are evaluated for anticonvulsant activity. After intraperitoneal (ip) injection to albino mice at a dose of 100 mg/kg body weight, synthesized quinazolin-4(3H)-ones (1–24) were examined in the maximal electroshock (MES) induced seizures and subcutaneous pentylenetetrazole (scPTZ) induced seizure [...] Read more.

A new series of quinazoline-4(3H)-ones are evaluated for anticonvulsant activity. After intraperitoneal (ip) injection to albino mice at a dose of 100 mg/kg body weight, synthesized quinazolin-4(3H)-ones (1–24) were examined in the maximal electroshock (MES) induced seizures and subcutaneous pentylenetetrazole (scPTZ) induced seizure models in mice. The Rotarod method was applied to determine the neurotoxicity. Most of the compounds displayed anticonvulsant activity in the scPTZ screen at a dose range of 0.204–0.376 mmol/mL. Out of twenty-four, compounds 8, 13 and 19 proved to be the most active with a remarkable protection (100%) against PTZ induced convulsions and four times more potent activity than ethosuximide. The structure-activity relationship concluded valuable pharmacophoric information, which was confirmed by the molecular docking studies using the target enzyme human carbon anhydrase II (HCA II). The studied quinazoline analogues suggested that the butyl substitution at position 3 has a significant effect on preventing the spread of seizure discharge and on raising the seizure threshold. However, benzyl substitution at position 3 has shown a strong anticonvulsant activity but with less seizure prevention compared to the butyl substitution. Full article

(This article belongs to the Special Issue Polypharmacology and Multitarget Drug Discovery)

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Open AccessFeature PaperArticle

Kinetics, Mechanism and Theoretical Studies of Norbornene-Ethylene Alternating Copolymerization Catalyzed by Organopalladium(II) Complexes Bearing Hemilabile α-Amino–pyridine

by Kuo-Hsuan Yu¹, Shou-Ling Huang¹, Yi-Hung Liu¹, Yu Wang¹, Shiuh-Tzung Liu¹, Yuan-Chung Cheng^1,*, Ya-Fan Lin^1,2,*

and Jwu-Ting Chen^1,*

¹ Department of Chemistry, National Taiwan University, Taipei 10617, Taiwan

² Department of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung 80708, Taiwan

Molecules 2017, 22(7), 1095; https://doi.org/10.3390/molecules22071095 - 30 Jun 2017

Cited by 10 | Viewed by 5720

Abstract

Cationic methylpalladium complexes bearing hemilabile bidentate α-amino–pyridines can serve as effective precursors for catalytic alternating copolymerization of norbornene (N) and ethylene (E), under mild conditions. The norbornyl palladium complexes in the formula of {[RHNCH₂(o-C₆H₄N)]Pd(C₇ [...] Read more.

Cationic methylpalladium complexes bearing hemilabile bidentate α-amino–pyridines can serve as effective precursors for catalytic alternating copolymerization of norbornene (N) and ethylene (E), under mild conditions. The norbornyl palladium complexes in the formula of {[RHNCH₂(o-C₆H₄N)]Pd(C₇H₁₀Me)(NCMe)}(BF₄) (R = ⁱPr (2a), ^tBu (2b), Ph (2c), 2,6-Me₂C₆H₃ (2d), 2,6-ⁱPr₂C₆H₃ (2e)) were synthesized via single insertion of norbornene into the corresponding methylpalladium complexes 1a–1e, respectively. Both square planar methyl and norbornyl palladium complexes exhibit facile equilibria of geometrical isomerization, via sterically-controlled amino decoordination–recoordination of amino–pyridine. Kinetic studies of E-insertion, N-insertion of complexes 1 and 2, and the geometric isomerization reactions have been examined by means of VT-NMR, and found in excellent agreement with the results estimated by DFT calculations. The more facile N-insertion in the cis-isomers, and ready geometric isomerization, cooperatively lead to a new mechanism that accounts for the novel catalytic formation of alternating COC. Full article

(This article belongs to the Special Issue Organometallic Catalysis for Olefin Polymerization/Oligomerization)

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Open AccessArticle

Enantioselective Michael Addition of Cyclic β-Diones to α,β-Unsaturated Enones Catalyzed by Quinine-Based Organocatalysts

by Qingqing Wang¹, Wei Wang¹, Ling Ye², Xuejun Yang¹, Xinying Li¹, Zhigang Zhao¹ and Xuefeng Li^1,*

¹ College of Chemistry and Environment Protection Engineering, Southwest Minzu University, Chengdu 610041, China

² Faculty of Geosciences and Environmental Engineering, Southwest Jiaotong University, Chengdu 610031, China

Molecules 2017, 22(7), 1096; https://doi.org/10.3390/molecules22071096 - 30 Jun 2017

Cited by 20 | Viewed by 5441

Abstract

An enantioselective (52–98% ee) Michael addition between cyclic β-diones and α,β-unsaturated enones was established in the presence of quinine-based primary amine or squaramide. A variety of cinnamones were smoothly converted into the desired 3,4-dihydropyrans in moderate to high yields (63–99%). Chalcones were also [...] Read more.

An enantioselective (52–98% ee) Michael addition between cyclic β-diones and α,β-unsaturated enones was established in the presence of quinine-based primary amine or squaramide. A variety of cinnamones were smoothly converted into the desired 3,4-dihydropyrans in moderate to high yields (63–99%). Chalcones were also suitable acceptors and gave rise to the expected adducts in satisfactory yields (31–99%). The resulting adducts readily underwent further modification to form fused 4H-pyran or 2,3-dihydrofuran. Full article

(This article belongs to the Special Issue Asymmetric Synthesis 2017)

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Open AccessArticle

Evaluation of Marine Microalga Diacronema vlkianum Biomass Fatty Acid Assimilation in Wistar Rats

by Cristina De Mello-Sampayo¹

, Angela Paterna¹, Ambra Polizzi¹, Diana Duarte², Irineu Batista², Rui Pinto¹, Patrícia Gonçalves³, Anabela Raymundo⁴, Ana P. Batista⁴, Luísa Gouveia⁵, Beatriz Silva-Lima¹ and Narcisa M. Bandarra^2,6,*

¹ Department of Pharmacological Sciences, iMed.ULisboa, Faculdade de Farmácia, Universidade de Lisboa, Lisbon 1649-003, Portugal

² Division of Aquaculture and Upgrading, Portuguese Institute for the Sea and Atmosphere (IPMA, IP), Rua Alfredo Magalhães Ramalho, Lisbon 1495-006, Portugal

³ Division of Modelling and Marine Resources, Portuguese Institute for the Sea and Atmosphere (IPMA, IP), Rua Alfredo Magalhães Ramalho, Lisbon 1495-006, Portugal

⁴ LEAF (Linking Landscape Environment Agriculture and Food), Research Center. Instituto Superior de Agronomia, Universidade de Lisboa. Tapada da Ajuda, 1349-017 Lisbon, Portugal

⁵ LNEG_Bioenergy Unit, Estrada do Paço do Lumiar, 22, 1649-038 Lisbon, Portugal

⁶ Interdisciplinary Centre of Marine and Environmental Research (CIIMAR/CIMAR), University of Porto, Rua dos Bragas 289, P 4050-123 Porto, Portugal

Molecules 2017, 22(7), 1097; https://doi.org/10.3390/molecules22071097 - 1 Jul 2017

Cited by 12 | Viewed by 4842

Abstract

Diacronema vlkianum is a marine microalgae for which supposed health promoting effects have been claimed based on its phytochemical composition. The potential use of its biomass as health ingredient, including detox-shakes, and the lack of bioavailability studies were the main concerns. In order [...] Read more.

Diacronema vlkianum is a marine microalgae for which supposed health promoting effects have been claimed based on its phytochemical composition. The potential use of its biomass as health ingredient, including detox-shakes, and the lack of bioavailability studies were the main concerns. In order to evaluate the microalgae-biomass assimilation and its health-benefits, single-dose (CD1-mice) studies were followed by 66-days repeated-dose study in Wistar rats with the highest tested single-dose of microalgae equivalent to 101 mg/kg eicosapentaenoic acid + docosahexaenoic acid (EPA+DHA). Microalgae-supplementation modulated EPA and docosapentaenoic acid enrichment at arachidonic acid content expenditure in erythrocytes and liver, while increasing EPA content of heart and adipose tissues of rats. Those fatty acid (FA) changes confirmed the D. vlkianum-biomass FA assimilation. The principal component analyses discriminated brain from other tissues, which formed two other groups (erythrocytes, liver, and heart separated from kidney and adipose tissues), pointing to a distinct signature of FA deposition for the brain and for the other organs. The improved serum lipid profile, omega-3 index and erythrocyte plasticity support the cardiovascular benefits of D. vlkianum. These results bolster the potential of D. vlkianum-biomass to become a “heart-healthy” food supplement providing a safe and renewable source of bioavailable omega-3 FA. Full article

(This article belongs to the Special Issue Natural Products and Chronic Diseases)

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Open AccessArticle

Antibacterial Activities of Pyrenylated Coumarins from the Roots of Prangos hulusii

by Nur Tan^1,*, Seçil Yazıcı-Tütüniş¹, Merve Bilgin², Emir Tan² and Mahmut Miski^1,*

¹ Department of Pharmacognosy, Faculty of Pharmacy, Istanbul University, Istanbul 34116, Turkey

² Department of Pharmaceutical Microbiology, Faculty of Pharmacy, Istanbul Yeni Yuzyil University, Istanbul 34110, Turkey

Molecules 2017, 22(7), 1098; https://doi.org/10.3390/molecules22071098 - 1 Jul 2017

Cited by 70 | Viewed by 6447

Abstract

The dichloromethane extract of the roots of Prangos hulusii, a recently described endemic species from Turkey, has yielded nine known and one new prenylated coumarins. The structures were elucidated by spectroscopic methods and direct comparison with the reference compounds where available. The [...] Read more.

The dichloromethane extract of the roots of Prangos hulusii, a recently described endemic species from Turkey, has yielded nine known and one new prenylated coumarins. The structures were elucidated by spectroscopic methods and direct comparison with the reference compounds where available. The root extract and its prenylated coumarins exhibit antimicrobial activity against nine standard and six clinically isolated strains at a concentration between 5 and 125 µg/mL. In particular, the new coumarin, 4′-senecioiloxyosthol (1), displayed 5 µg/mL MIC (Minimum Inhibitory Concentration) value against Bacillus subtilis ATCC 9372, murraol (4) and auraptenol (5) showed 63 µg/mL MIC value against Klebsiella pneumoniae ATCC 4352 and Bacillus subtilis ATCC 9372, and isoimperatorin (9) exhibited 16 µg/mL MIC value. Full article

(This article belongs to the Collection Bioactive Compounds)

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Open AccessArticle

Synthesis and Evaluation of N-(3-Trifluoroacetyl-indol-7-yl) Acetamides for Potential In Vitro Antiplasmodial Properties

by Malose J. Mphahlele^1,*

, Mmakwena M. Mmonwa¹ and Yee Siew Choong²

¹ Department of Chemistry, College of Science, Engineering and Technology, University of South Africa, Private Bag X06, Florida 1710, South Africa

² Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia, 11800 Minden, Penang, Malaysia

Molecules 2017, 22(7), 1099; https://doi.org/10.3390/molecules22071099 - 2 Jul 2017

Cited by 7 | Viewed by 4283

Abstract

A series of novel N-((2,5-diaryl-3-trifluoroacetyl)-1H-indol-7-yl)acetamides has been prepared via a successive and one-pot reaction sequence involving initial trifluoroacetic acid-mediated Beckmann rearrangement of the oximes derived from the 1-(2,5-diaryl-1H-indol-7-yl)ethanones, followed by trifluoroacetylation of the incipient N-(2,5-diaryl-1H-indol-7-yl)-acetamides [...] Read more.

A series of novel N-((2,5-diaryl-3-trifluoroacetyl)-1H-indol-7-yl)acetamides has been prepared via a successive and one-pot reaction sequence involving initial trifluoroacetic acid-mediated Beckmann rearrangement of the oximes derived from the 1-(2,5-diaryl-1H-indol-7-yl)ethanones, followed by trifluoroacetylation of the incipient N-(2,5-diaryl-1H-indol-7-yl)-acetamides with trifluoroacetic anhydride. The prepared compounds were evaluated for potential in vitro antiplasmodial properties. Preliminary results from antiplasmodial activity against the chloroquine-sensitive 3D7 strain of Plasmodium falciparum revealed that a combination of 2-(4-flurophenyl)- and 5-(4-fluorophenyl) or 2-(4-flurophenyl)- and 4-fluorostyryl groups in compounds 3(a,f) and 4(a,g), for example, is required for biological activity for both series of compounds. Their possible mode of action against the plasmodial parasite is explained theoretically through molecular docking of the most active compounds against the parasite lactate dehydrogenase (pLDH). These compounds were docked at the entrance of NAD+ in pLDH presumably hindering entry of lactate to cause the observed inhibition effect of pLDH. The four compounds were found to exhibit low toxicity against monkey kidney Vero cells at the highest concentrations tested. Full article

(This article belongs to the Section Bioorganic Chemistry)

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Open AccessArticle

Phytochemical Analysis and Antimicrobial Activity of Myrcia tomentosa (Aubl.) DC. Leaves

by Fabyola Amaral Da Silva Sa^1,3, Joelma Abadia Marciano De Paula², Pierre Alexandre Dos Santos³, Leandra De Almeida Ribeiro Oliveira³, Gerlon De Almeida Ribeiro Oliveira⁴, Luciano Morais Liao⁴, Jose Realino De Paula^3,* and Maria Do Rosario Rodrigues Silva^1,*

¹ Institute of Tropical Pathology and Public Health, Federal University of Goias, Goiânia 74605-050, Brazil

² Unit of Exact and Technologic Sciences, Goias State University, Anápolis 75132-400, Brazil

³ Faculty of Pharmacy, Federal University of Goias, Goiânia 74605-170, Brazil

⁴ Chemistry Institute, Federal University of Goiás, Goiânia 74690-900, Brazil

Molecules 2017, 22(7), 1100; https://doi.org/10.3390/molecules22071100 - 4 Jul 2017

Cited by 35 | Viewed by 6426

Abstract

This work describes the isolation and structural elucidation of compounds from the leaves of Myrcia tomentosa (Aubl.) DC. (goiaba-brava) and evaluates the antimicrobial activity of the crude extract, fractions and isolated compounds against bacteria and fungi. Column chromatography was used to fractionate and [...] Read more.

This work describes the isolation and structural elucidation of compounds from the leaves of Myrcia tomentosa (Aubl.) DC. (goiaba-brava) and evaluates the antimicrobial activity of the crude extract, fractions and isolated compounds against bacteria and fungi. Column chromatography was used to fractionate and purify the extract of the M. tomentosa leaves and the chemical structures of the compounds were determined using spectroscopic techniques. The antibacterial and antifungal activities were assessed using the broth microdilution method. The phytochemical investigation isolated 11 compounds: α-bisabolol, α-bisabolol oxide B, α-cadinol, β-sitosterol, n-pentacosane, n-tetracosane, quercetin, kaempferol, avicularin, juglanin and guaijaverin. The crude ethanolic extract and its fractions were tested against 15 bacteria and 9 yeasts. The crude extract inhibited the in vitro growth of yeasts at concentration of 4 to 32 μg/mL. The hexane, dichloromethane, ethyl acetate and aqueous fractions inhibited Candida sp. at concentrations of 4 to 256 μg/mL, whereas the Cryptococcus sp. isolates were inhibited only by the hexane and dichloromethane fractions in minimal inhibitory concentrations (MICs) at 16 to 64 μg/mL. The flavonoid quercetin-3-O-α-arabinofuranose (avicularin) was the most active compound, inhibiting Candida species in concentrations of 2 to 32 μg/mL. The MIC values suggest potential activity of this plant species against yeast. Full article

(This article belongs to the Collection Bioactive Compounds)

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Open AccessArticle

Sites for Dynamic Protein-Carbohydrate Interactions of O- and C-Linked Mannosides on the E. coli FimH Adhesin

by Mohamed Touaibia^1,2,†

, Eva-Maria Krammer^3,†, Tze C. Shiao¹, Nao Yamakawa³, Qingan Wang¹, Anja Glinschert⁴, Alex Papadopoulos¹, Leila Mousavifar¹

, Emmanuel Maes³, Stefan Oscarson⁴, Gerard Vergoten³, Marc F. Lensink³

, René Roy^1,* and Julie Bouckaert^3,*

¹ Pharmaqam, Department of Chemistry, Université du Québec à Montréal, P. O. Box 8888, Succ. Centre-ville, Montréal, QC H3C 3P8, Canada

² Department of Chemistry and Biochemistry, Université de Moncton, Moncton, NB E1A 3E9, Canada

³ Unité de Glycobiologie Structurale et Fonctionnelle (UGSF), UMR8576 du CNRS, Université de Lille, F-59000 Lille, France

⁴ Center for Synthesis and Chemical Biology (CSCB), University College Dublin, Belfield, Dublin 4, Ireland

^† These authors contributed equally to this work.

Molecules 2017, 22(7), 1101; https://doi.org/10.3390/molecules22071101 - 3 Jul 2017

Cited by 23 | Viewed by 7475

Abstract

Antagonists of the Escherichia coli type-1 fimbrial adhesin FimH are recognized as attractive alternatives for antibiotic therapies and prophylaxes against acute and recurrent bacterial infections. In this study α-d-mannopyranosides O- or C-linked with an alkyl, alkene, alkyne, thioalkyl, amide, [...] Read more.

Antagonists of the Escherichia coli type-1 fimbrial adhesin FimH are recognized as attractive alternatives for antibiotic therapies and prophylaxes against acute and recurrent bacterial infections. In this study α-d-mannopyranosides O- or C-linked with an alkyl, alkene, alkyne, thioalkyl, amide, or sulfonamide were investigated to fit a hydrophobic substituent with up to two aryl groups within the tyrosine gate emerging from the mannose-binding pocket of FimH. The results were summarized into a set of structure-activity relationships to be used in FimH-targeted inhibitor design: alkene linkers gave an improved affinity and inhibitory potential, because of their relative flexibility combined with a favourable interaction with isoleucine-52 located in the middle of the tyrosine gate. Of particular interest is a C-linked mannoside, alkene-linked to an ortho-substituted biphenyl that has an affinity similar to its O-mannosidic analog but superior to its para-substituted analog. Docking of its high-resolution NMR solution structure to the FimH adhesin indicated that its ultimate, ortho-placed phenyl ring is able to interact with isoleucine-13, located in the clamp loop that undergoes conformational changes under shear force exerted on the bacteria. Molecular dynamics simulations confirmed that a subpopulation of the C-mannoside conformers is able to interact in this secondary binding site of FimH. Full article

(This article belongs to the Special Issue Protein-Carbohydrate Interactions)

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A Novel Synthesis of 4-Acetoxyl 5(4H)-Oxazolones by Direct α-Oxidation of N-Benzoyl Amino-Acid Using Hypervalent Iodine

by Gang Wen, Wen-Xuan Zhang^*

and Song Wu^*

State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China

Molecules 2017, 22(7), 1102; https://doi.org/10.3390/molecules22071102 - 3 Jul 2017

Cited by 3 | Viewed by 5913

Abstract

We have developed a new method to prepare 4-acetoxy substituted 5(4H)-oxazolones by direct oxidation of N-benzoyl amino-acids using hypervalent iodine. The method is efficient, economical and easy to perform for the synthesis of quaternary substituted amino acid derivatives. We used [...] Read more.

We have developed a new method to prepare 4-acetoxy substituted 5(4H)-oxazolones by direct oxidation of N-benzoyl amino-acids using hypervalent iodine. The method is efficient, economical and easy to perform for the synthesis of quaternary substituted amino acid derivatives. We used online FTIR monitoring techniques to analyze the reaction, and gave a plausible reaction mechanism. Full article

(This article belongs to the Section Organic Chemistry)

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Synthesis and Fungicidal Activity of 1-(Carbamoylmethyl)-2-aryl-3,1-benzoxazines

by Zi-Long Tang^1,2,*

, Lian Wang^1,2, Jing-Zhao Tan^1,2, Yi-Chao Wan¹ and Yin-Chun Jiao²

¹ Key Laboratory of Theoretical Organic Chemistry and Functional Molecule of Ministry of Education, Hunan University of Science and Technology, Xiangtan 411201, China

² School of Chemistry and Chemical Engineering, Hunan University of Science and Technology, Xiangtan 411201, China

Molecules 2017, 22(7), 1103; https://doi.org/10.3390/molecules22071103 - 6 Jul 2017

Cited by 9 | Viewed by 3553

Abstract

A series of new 1-(carbamoylmethyl)-2-aryl-3,1-benzoxazines were prepared in moderate to good yields by BF₃·OEt₂-catalyzed reactions of aromatic aldehydes with 2-(N-substituted carbamoylmethylamino)benzyl alcohols. The structures of the target compounds were confirmed by IR, ¹H-NMR, ¹³C-NMR, and [...] Read more.

A series of new 1-(carbamoylmethyl)-2-aryl-3,1-benzoxazines were prepared in moderate to good yields by BF₃·OEt₂-catalyzed reactions of aromatic aldehydes with 2-(N-substituted carbamoylmethylamino)benzyl alcohols. The structures of the target compounds were confirmed by IR, ¹H-NMR, ¹³C-NMR, and elemental analyses. The fungicidal activities of the target compounds against plant fungi were preliminarily evaluated, and some of them exhibited good activity. Full article

(This article belongs to the Section Organic Chemistry)

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L1210 Cells Overexpressing ABCB1 Drug Transporters Are Resistant to Inhibitors of the N- and O-glycosylation of Proteins

by Lucia Pavlikova¹, Mario Seres¹, Milan Hano¹, Viera Bohacova¹, Ivana Sevcikova^1,2, Tomas Kyca^1,2, Albert Breier^2,*

and Zdena Sulova^1,*

¹ Institute of Molecular Physiology and Genetics, Centre of Bioscience, Slovak Academy of Sciences, Dúbravska cesta 9, 84005 Bratislava, Slovakia

² Institute of Biochemistry and Microbiology, Faculty of Chemical and Food Technology, Slovak University of Technology, Radlinského 9, 81237 Bratislava, Slovakia

Molecules 2017, 22(7), 1104; https://doi.org/10.3390/molecules22071104 - 3 Jul 2017

Cited by 6 | Viewed by 4886

Abstract

Overexpression of P-glycoprotein (P-gp, drug transporter) in neoplastic cells is the most frequently observed molecular cause of multidrug resistance. Here, we show that the overexpression of P-gp in L1210 cells leads to resistance to tunicamycin and benzyl 2-acetamido-2-deoxy-α-d-galactopyranoside (GalNAc-α-O-benzyl). [...] Read more.

Overexpression of P-glycoprotein (P-gp, drug transporter) in neoplastic cells is the most frequently observed molecular cause of multidrug resistance. Here, we show that the overexpression of P-gp in L1210 cells leads to resistance to tunicamycin and benzyl 2-acetamido-2-deoxy-α-d-galactopyranoside (GalNAc-α-O-benzyl). Tunicamycin induces both glycosylation depression and ubiquitination improvement of P-gp. However, the latter is not associated with large increases in molecular mass as evidence for polyubiquitination. Therefore, P-gp continues in maturation to an active membrane efflux pump rather than proteasomal degradation. P-gp-positive L1210 cells contain a higher quantity of ubiquitin associated with cell surface proteins than their P-gp-negative counterparts. Thus, P-gp-positive cells use ubiquitin signaling for correct protein folding to a higher extent than P-gp-negative cells. Elevation of protein ubiquitination after tunicamycin treatment in these cells leads to protein folding rather than protein degradation, resulting at least in the partial lack of cell sensitivity to tunicamycin in L1210 cells after P-gp expression. In contrast to tunicamycin, to understand why P-gp-positive cells are resistant to GalNAc-α-O-benzyl, further research is needed. Full article

(This article belongs to the Special Issue Protein-Carbohydrate Interactions)

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Subcritical Water Technology for Extraction of Phenolic Compounds from Chlorella sp. Microalgae and Assessment on Its Antioxidant Activity

by Siti Maisurah Zakaria¹, Siti Mazlina Mustapa Kamal^1,*, Mohd Razif Harun², Rozita Omar² and Shamsul Izhar Siajam²

¹ Department of Process and Food Engineering, Faculty of Engineering, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia;

² Department of Chemical and Environmental Engineering, Faculty of Engineering, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia

Molecules 2017, 22(7), 1105; https://doi.org/10.3390/molecules22071105 - 3 Jul 2017

Cited by 56 | Viewed by 7394

Abstract

Chlorella sp. microalgae is a potential source of antioxidants and natural bioactive compounds used in the food and pharmaceutical industries. In this study, a subcritical water (SW) technology was applied to determine the phenolic content and antioxidant activity of Chlorella sp. [...] Read more.

Chlorella sp. microalgae is a potential source of antioxidants and natural bioactive compounds used in the food and pharmaceutical industries. In this study, a subcritical water (SW) technology was applied to determine the phenolic content and antioxidant activity of Chlorella sp. This study focused on maximizing the recovery of Chlorella sp. phenolic content and antioxidant activity measured by 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay as a function of extraction temperature (100–250 °C), time (5–20 min) and microalgae concentration (5–20 wt. %) using response surface methodology. The optimal operating conditions for the extraction process were found to be 5 min at 163 °C with 20 wt. % microalgae concentration, which resulted in products with 58.73 mg gallic acid equivalent (GAE)/g phenolic content and 68.5% inhibition of the DPPH radical. Under optimized conditions, the experimental values were in close agreement with values predicted by the model. The phenolic content was highly correlated (R² = 0.935) with the antioxidant capacity. Results indicated that extraction by SW technology was effective and that Chlorella sp. could be a useful source of natural antioxidants. Full article

(This article belongs to the Special Issue Green Extraction of Natural Product: Innovative Techniques, Alternative Solvents and Original Procedures)

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Open AccessArticle

Newly Synthesized Doxorubicin Complexes with Selected Metals—Synthesis, Structure and Anti-Breast Cancer Activity

by Agata Jabłońska-Trypuć^1,*

, Grzegorz Świderski², Rafał Krętowski³

and Włodzimierz Lewandowski²

¹ Division of Sanitary Biology and Biotechnology, Faculty of Civil Engineering and Environmental Engineering, Białystok University of Technology, Wiejska 45E Street, Białystok 15-351, Poland

² Division of Chemistry, Bialystok University of Technology, Białystok 15-351, Poland

³ Department of Pharmaceutical Biochemistry, Medical University of Białystok, Białystok 15-222, Poland

Molecules 2017, 22(7), 1106; https://doi.org/10.3390/molecules22071106 - 4 Jul 2017

Cited by 59 | Viewed by 7963

Abstract

Doxorubicin (DOX) is very effective chemotherapeutic agent, however it has several major drawbacks. Therefore the motivation for developing novel drug complexes as anticancer agents with different mechanism of action has arisen. The aim of the present study was to evaluate the influence of [...] Read more.

Doxorubicin (DOX) is very effective chemotherapeutic agent, however it has several major drawbacks. Therefore the motivation for developing novel drug complexes as anticancer agents with different mechanism of action has arisen. The aim of the present study was to evaluate the influence of newly synthesized DOX complexes with selected metals (Mg, Mn, Co, Ni, Fe, Cu, Zn) on apoptosis, cell cycle, viability, proliferation and cytotoxicity in the breast cancer cell line MCF-7. Complexation of DOX with metals has likewise been the subject of our research. The current work showed that the tested bivalent metals at a given pH condition formed metal:DOX complexes in a ratio of 2:1, while iron complexes with DOX in a ratio of 3:1. The studies also showed that selected metal-DOX complexes (Mg-DOX, Mn-DOX, Ni-DOX) at 0.5 µM concentration significantly decreased cell viability and proliferation, however they increased caspase 7 activity. Results also indicated that studied metal-DOX complexes showed high cytotoxicity in MCF-7 cells. Therefore they were chosen for cell cycle check-points and apoptosis/necrosis analysis studied by flow cytometry. Obtained results suggest that doxorubicin complexed by specified metals can be considered as a potential anti-breast cancer agent, which is characterized by a higher efficacy than a parent drug. Full article

(This article belongs to the Collection Efficient Pharmaceutical and Chemical Approaches for Anticancer Therapy: Design, Preliminary Evaluations, and Further Developments)

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Open AccessReview

Synthesis and Modification of Clinoptilolite

by Pavlina Ambrozova¹

, Jindrich Kynicky^1,2,*, Tomas Urubek^1,2 and Vinh Dinh Nguyen^2,3

¹ Faculty of Forestry and Wood Technology, Mendel University in Brno, Zemedelska 1, 61300 Brno, Czech Republic

² Central European Institute of Technology, Brno University of Technology, Purkynova 656/123, 61200 Brno, Czech Republic

³ Faculty of Chemistry, Thai Nguyen University of Sciences, Tan Thinh Ward, 251580 Thai Nguyen, Vietnam

Molecules 2017, 22(7), 1107; https://doi.org/10.3390/molecules22071107 - 4 Jul 2017

Cited by 57 | Viewed by 8914

Abstract

Clinoptilolite is a natural mineral with exceptional physical characteristics resulting from its special crystal structure, mainstreamed into a large zeolite group called heulandites. An overall view of the research related to the synthesis, modification and application of synthetic clinoptilolite is presented. A single [...] Read more.

Clinoptilolite is a natural mineral with exceptional physical characteristics resulting from its special crystal structure, mainstreamed into a large zeolite group called heulandites. An overall view of the research related to the synthesis, modification and application of synthetic clinoptilolite is presented. A single phase of clinoptilolite can be hydrothermally synthesized for 1–10 days in an autoclave from various silica, alumina, and alkali sources with initial Si/Al ratio from 3.0 to 5.0 at a temperature range from 120 to 195 °C. Crystallization rate and crystallinity of clinoptilolite can be improved by seeding. The modification of clinoptilolite has received noticeable attention from the research community, since modified forms have specific properties and therefore their area of application has been broadening. This paper provides a review of the use of organic compounds such as quarter alkyl ammonium, polymer, amine and inorganic species used in the modification process, discusses the processes and mechanisms of clinoptilolite modification, and identifies research gaps and new perspectives. Full article

(This article belongs to the Special Issue Zeolites and Related Nanoporous Materials: Synthesis, Characterization and Applications in Catalysis and Green Chemistry)

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Open AccessArticle

The [Mo₆Cl₁₄]²⁻ Cluster is Biologically Secure and Has Anti-Rotavirus Activity In Vitro

by Edgardo Rojas-Mancilla¹, Alexis Oyarce², Viviana Verdugo², Cesar Morales-Verdejo³, Cesar Echeverria³, Felipe Velásquez⁴, Jonas Chnaiderman⁴, Fernando Valiente-Echeverría⁴ and Rodrigo Ramirez-Tagle^5,*

¹ Departamento de Ciencias Químicas y Biológicas, Universidad Bernardo O Higgins, General Gana 1702, Santiago 8370854, Chile

² Escuela de Tecnología Médica, Universidad Bernardo O Higgins, General Gana 1702, Santiago 8370854, Chile

³ Centro Integrativo de Biología y Química Aplicada, Universidad Bernardo O Higgins, General Gana 1702, Santiago 8370854, Chile

⁴ Instituto de Ciencias Biomédicas, Programa de Virología, Universidad de Chile, Avda, Independencia 1027, Independencia 8380453, Chile

⁵ Facultad de Ingeniería, Ciencia y Tecnología, Universidad Bernardo O Higgins, Avenida Viel 1497, Santiago 8370993, Chile

Molecules 2017, 22(7), 1108; https://doi.org/10.3390/molecules22071108 - 5 Jul 2017

Cited by 6 | Viewed by 5259

Abstract

The molybdenum cluster [Mo₆Cl₁₄]²⁻ is a fluorescent component with potential for use in cell labelling and pharmacology. Biological safety and antiviral properties of the cluster are as yet unknown. Here, we show the effect of acute exposition of [...] Read more.

The molybdenum cluster [Mo₆Cl₁₄]²⁻ is a fluorescent component with potential for use in cell labelling and pharmacology. Biological safety and antiviral properties of the cluster are as yet unknown. Here, we show the effect of acute exposition of human cells and red blood cells to the molybdenum cluster and its interaction with proteins and antiviral activity in vitro. We measured cell viability of HepG2 and EA.hy926 cell lines exposed to increasing concentrations of the cluster (0.1 to 250 µM), by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay. Hemolysis and morphological alterations of red blood cells, obtained from healthy donors, exposed to the cluster (10 to 200 µM) at 37 °C were analyzed. Furthermore, quenching of tryptophan residues of albumin was performed. Finally, plaque formation by rotavirus SA11 in MA104 cells treated with the cluster (100 to 300 µM) were analyzed. We found that all doses of the cluster showed similar cell viability, hemolysis, and morphology values, compared to control. Quenching of tryptophan residues of albumin suggests a protein-cluster complex formation. Finally, the cluster showed antiviral activity at 300 µM. These results indicate that the cluster [Mo₆Cl₁₄]²⁻ could be intravenously administered in animals at therapeutic doses for further in vivo studies and might be studied as an antiviral agent. Full article

(This article belongs to the Special Issue Metal Based Drugs: Opportunities and Challenges)

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Open AccessArticle

Synthesis and Evaluation of New Oxadiazole, Thiadiazole, and Triazole Derivatives as Potential Anticancer Agents Targeting MMP-9

by Ahmet Özdemir^1,*, Belgin Sever¹

, Mehlika Dilek Altıntop¹, Halide Edip Temel², Özlem Atlı³, Merve Baysal³ and Fatih Demirci⁴

¹ Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, Eskişehir 26470, Turkey

² Department of Biochemistry, Faculty of Pharmacy, Anadolu University, Eskişehir 26470, Turkey

³ Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Anadolu University, Eskişehir 26470, Turkey

⁴ Department of Pharmacognosy, Faculty of Pharmacy, Anadolu University, Eskişehir 26470, Turkey

Molecules 2017, 22(7), 1109; https://doi.org/10.3390/molecules22071109 - 4 Jul 2017

Cited by 36 | Viewed by 5202

Abstract

Matrix metalloproteinases (MMPs) are important proteases involved in tumor progression including angiogenesis, tissue invasion, and migration. Therefore, MMPs have been reported as potential diagnostic and prognostic biomarkers in many types of cancer. New oxadiazole, thiadiazole, and triazole derivatives were synthesized and evaluated for [...] Read more.

Matrix metalloproteinases (MMPs) are important proteases involved in tumor progression including angiogenesis, tissue invasion, and migration. Therefore, MMPs have been reported as potential diagnostic and prognostic biomarkers in many types of cancer. New oxadiazole, thiadiazole, and triazole derivatives were synthesized and evaluated for their anticancer effects on A549 human lung adenocarcinoma and C6 rat glioma cell lines. In order to examine the relationship between their anticancer activity and MMP-9, the compounds were evaluated for their inhibitory effects on MMPs. N-(1,3-Benzodioxol-5-ylmethyl)-2-{[5,[5-(((5,6,7,8-tetrahydronaphthalen-2-yl)oxy)methyl)-1,3,4-oxadiazol-2-yl]thio}acetamide (8) and N-(1,3-benzodioxol-5-ylmethyl)-2-[(5-phenyl-1,3,4-oxadiazol-2-yl)thio]acetamide (9) revealed promising cytotoxic effects on A549 and C6 cell lines similar to cisplatin without causing any toxicity towards NIH/3T3 mouse embryonic fibroblast cell line. Compounds 8 and 9 were also the most effective MMP-9 inhibitors in this series. Moreover, docking studies pointed out that compounds 8 and 9 had good affinity to the active site of the MMP-9 enzyme. The molecular docking and in vitro studies suggest that the MMP-9 inhibitory effects of compounds 8 and 9 may play an important role in lung adenocarcinoma and glioma treatment. Full article

(This article belongs to the Section Medicinal Chemistry)

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Open AccessArticle

Ranatensin-HL: A Bombesin-Related Tridecapeptide from the Skin Secretion of the Broad-Folded Frog, Hylarana latouchii

by Yan Lin^1,2,*

, Tianbao Chen²

, Mei Zhou²

, Lei Wang², Songkun Su^1,* and Chris Shaw²

¹ College of Bee Science, Fujian Agriculture and Forestry University, Fuzhou 350002, China

² Natural Drug Discovery Group, School of Pharmacy, Queen’s University, Belfast BT9 7BL, Northern Ireland, UK

Molecules 2017, 22(7), 1110; https://doi.org/10.3390/molecules22071110 - 4 Jul 2017

Cited by 6 | Viewed by 4341

Abstract

Bombesin-related peptides are a family of peptides whose prototype was discovered in amphibian skin and which exhibit a wide range of biological activities. Since the initial isolation of bombesin from Bombina bombina skin, diverse forms of bombesin-related peptides have been found in the [...] Read more.

Bombesin-related peptides are a family of peptides whose prototype was discovered in amphibian skin and which exhibit a wide range of biological activities. Since the initial isolation of bombesin from Bombina bombina skin, diverse forms of bombesin-related peptides have been found in the skins across Anura. In this study, a novel bombesin-related peptide of the ranatensin subfamily, named ranatensin-HL, was structurally-characterised from the skin secretion of the broad-folded frog, Hylarana latouchii, through combination of molecular cloning and mass spectrometric methodologies. It is composed of 13 amino acid residues, pGlu-RAGNQWAIGHFM-NH₂, and resembles an N-terminally extended form of Xenopus neuromedin B. Ranatensin-HL and its C-terminal decapeptide (ranatensin-HL-10) were chemically synthesised and subjected to in vitro smooth muscle assays in which they were found to display moderate stimulatory effects on rat urinary bladder and uterus smooth muscles with EC₅₀ values in the range of 1–10 nM. The prepro-ranatensin-HL was highly homological to a bombesin-like peptide from Rana catesbeiana at both nucleotide and amino acid levels, which might provide a clue for the taxonomic classification of ranid frogs in the future. Full article

(This article belongs to the Special Issue Bioactive Natural Peptides As A Pipeline For Therapeutics)

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Open AccessArticle

Substituent Effects on the Stability of Thallium and Phosphorus Triple Bonds: A Density Functional Study

by Jia-Syun Lu¹, Ming-Chung Yang¹ and Ming-Der Su^1,2,*

¹ Department of Applied Chemistry, National Chiayi University, Chiayi 60004, Taiwan

² Department of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung 80708, Taiwan

Molecules 2017, 22(7), 1111; https://doi.org/10.3390/molecules22071111 - 5 Jul 2017

Cited by 3 | Viewed by 4106

Abstract

Three computational methods (M06-2X/Def2-TZVP, B3PW91/Def2-TZVP and B3LYP/LANL2DZ+dp) were used to study the effect of substitution on the potential energy surfaces of RTl≡PR (R = F, OH, H, CH₃, SiH₃, SiMe(SitBu₃)₂, SiiPrDis [...] Read more.

Three computational methods (M06-2X/Def2-TZVP, B3PW91/Def2-TZVP and B3LYP/LANL2DZ+dp) were used to study the effect of substitution on the potential energy surfaces of RTl≡PR (R = F, OH, H, CH₃, SiH₃, SiMe(SitBu₃)₂, SiiPrDis₂, Tbt (=C₆H₂-2,4,6-(CH(SiMe₃)₂)₃), and Ar* (=C₆H₃-2,6-(C₆H₂-2, 4,6-i-Pr₃)₂)). The theoretical results show that these triply bonded RTl≡PR compounds have a preference for a bent geometry (i.e., ∠R⎼Tl⎼P ≈ 180° and ∠Tl⎼P⎼R ≈ 120°). Two valence bond models are used to interpret the bonding character of the Tl≡P triple bond. One is model [I], which is best described as TlP. This interprets the bonding conditions for RTl≡PR molecules that feature small ligands. The other is model [II], which is best represented as TlP. This explains the bonding character of RTl≡PR molecules that feature large substituents. Irrespective of the types of substituents used for the RTl≡PR species, the theoretical investigations (based on the natural bond orbital, the natural resonance theory, and the charge decomposition analysis) demonstrate that their Tl≡P triple bonds are very weak. However, the theoretical results predict that only bulkier substituents greatly stabilize the triply bonded RTl≡PR species, from the kinetic viewpoint. Full article

(This article belongs to the Section Computational and Theoretical Chemistry)

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Efficiency of Dinucleosides as the Backbone to Pre-Organize Multi-Porphyrins and Enhance Their Stability as Sandwich Type Complexes with DABCO

by Sonja Merkaš^1,2,†, Souhaila Bouatra¹, Régis Rein¹, Ivo Piantanida²

, Mladen Zinic² and Nathalie Solladié^1,*

¹ CNRS, LCC (Laboratoire de Chimie de Coordination), 205 Route de Narbonne, 31077 Toulouse France and Université de Toulouse, UPS, INPT, 31077 Toulouse, France

² Laboratory of Supramolecular and Nucleoside Chemistry, Rudjer Boskovic Institute, Bijenicka cesta 54, HR-10002 Zagreb, Croatia

^† Current Address: Novartis Pharma AG, CH-4056 Basel, Switzerland

Molecules 2017, 22(7), 1112; https://doi.org/10.3390/molecules22071112 - 6 Jul 2017

Cited by 3 | Viewed by 4722

Abstract

Flexible linkers such as uridine or 2′-deoxyuridine pre-organize bis-porphyrins in a face-to-face conformation, thus forming stable sandwich complexes with a bidentate base such as 1,4-diazabicyclo[2.2.2]octane (DABCO). Increased stability can be even greater when a dinucleotide linker is used. Such pre-organization increases the association [...] Read more.

Flexible linkers such as uridine or 2′-deoxyuridine pre-organize bis-porphyrins in a face-to-face conformation, thus forming stable sandwich complexes with a bidentate base such as 1,4-diazabicyclo[2.2.2]octane (DABCO). Increased stability can be even greater when a dinucleotide linker is used. Such pre-organization increases the association constant by one to two orders of magnitude when compared to the association constant of DABCO with a reference porphyrin. Comparison with rigid tweezers shows a better efficiency of nucleosidic dimers. Thus, the choice of rigid spacers is not the only way to pre-organize bis-porphyrins, and well-chosen nucleosidic linkers offer an interesting option for the synthesis of such devices. Full article

(This article belongs to the Special Issue Porphyrins and Phthalocyanines: Synthesis, Properties and Applications)

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Open AccessArticle

Proteomics Analysis Reveals an Important Role for the PPAR Signaling Pathway in DBDCT-Induced Hepatotoxicity Mechanisms

by Yunlan Li^1,2,*, Xinxin Liu¹, Lin Niu¹ and Qingshan Li^1,2,*

¹ School of Pharmaceutical Science, Shanxi Medical University, Taiyuan 030001, China

² Department of Traditional Chinese Medicine, Shanxi University of Traditional Chinese Medicine, Taiyuan 030001, China

Molecules 2017, 22(7), 1113; https://doi.org/10.3390/molecules22071113 - 6 Jul 2017

Cited by 16 | Viewed by 6388

Abstract

A patented organotin di-n-butyl-di-(4-chlorobenzohydroxamato)tin (DBDCT) with high a antitumor activity was designed, however, its antitumor and toxic mechanisms have not yet been clearly illustrated. Hepatic proteins of DBDCT-treated rats were identified and analyzed using LC–MS/MS with label-free quantitative technology. In total, [...] Read more.

A patented organotin di-n-butyl-di-(4-chlorobenzohydroxamato)tin (DBDCT) with high a antitumor activity was designed, however, its antitumor and toxic mechanisms have not yet been clearly illustrated. Hepatic proteins of DBDCT-treated rats were identified and analyzed using LC–MS/MS with label-free quantitative technology. In total, 149 differentially expressed proteins were successfully identified. Five protein and mRNA expressions were involved in the peroxisome proliferator-activated receptor (PPAR) signaling pathway, including a scavenger receptor (CD36), adipocyte fatty acid binding protein 4 (FABP4), enoyl-CoA hydratase (EHHADH), acetyl-CoA acyltransferase 1 (ACAA1), and phosphoenolpyruvate carboxykinase (PEPCK) in DBDCT-treated Rat Liver (BRL) cells. PPAR-α and PPAR-λ were also significantly decreased at both protein and mRNA levels. Furthermore, compared with the DBDCT treatment group, a special blocking agent of PPAR-λ T0070907 was used to evaluate the relationship between PPAR-λ and its downstream genes. Our studies indicated that DBDCT may serve as a modulator of PPAR-λ, further up-regulating CD36, FABP4 and EHHADH on the PPAR signal pathway. Full article

(This article belongs to the Section Medicinal Chemistry)

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Open AccessArticle

Antioxidant Capacity, Anticancer Ability and Flavonoids Composition of 35 Citrus (Citrus reticulata Blanco) Varieties

by Yue Wang¹, Jing Qian¹, Jinping Cao^1,2, Dengliang Wang³, Chunrong Liu³, Rongxi Yang⁴, Xian Li¹ and Chongde Sun^1,*

¹ Laboratory of Fruit Quality Biology/The State Agriculture Ministry Laboratory of Horticultural Plant Growth, Development and Quality Improvement, Zhejiang University, Zijingang Campus, Hangzhou 310058, China

² Horticulture Research Institute, Taizhou Academy of Agricultural Sciences, Linhai 317000, China

³ Citrus Research Institute, Quzhou Academy of Agricultural Sciences, Quzhou 324000, China

⁴ Forestry Special Production Technology Promotion Center, Xiangshan Bureau of Agriculture and Forestry, Ningbo 315700, China

Molecules 2017, 22(7), 1114; https://doi.org/10.3390/molecules22071114 - 5 Jul 2017

Cited by 107 | Viewed by 9241

Abstract

Citrus (Citrus reticulate Blanco) is one of the most commonly consumed and widely distributed fruit in the world, which is possessing extensive bioactivities. Present study aimed to fully understand the flavonoids compositions, antioxidant capacities and in vitro anticancer abilities of different citrus [...] Read more.

Citrus (Citrus reticulate Blanco) is one of the most commonly consumed and widely distributed fruit in the world, which is possessing extensive bioactivities. Present study aimed to fully understand the flavonoids compositions, antioxidant capacities and in vitro anticancer abilities of different citrus resources. Citrus fruits of 35 varieties belonging to 5 types (pummelos, oranges, tangerines, mandarins and hybrids) were collected. Combining li quid chromatography combined with electrospray ionization mass spectrometry (LC-ESI-MS/MS) and ultra-performance liquid chromatography combined with diode array detector (UPLC-DAD), a total of 39 flavonoid compounds were identified, including 4 flavones, 9 flavanones and 26 polymethoxylated flavonoids (PMFs). Each citrus fruit was examined and compared by 4 parts, flavedo, albedo, segment membrane and juice sacs. The juice sacs had the lowest total phenolics, following by the segment membrane. Four antioxidant traits including 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, ferric reducing antioxidant power (FRAP), oxygen radical absorbance capacity (ORAC) and cupric reducing antioxidant capacity (CUPRAC) were applied for the antioxidant capacities evaluation. Three gastric cancer cell lines, SGC-7901, BGC-823 and AGS were applied for the cytotoxicity evaluation. According to the results of correlation analysis, phenolics compounds might be the main contributor to the antioxidant activity of citrus extracts, while PMFs existing only in the flavedo might be closely related to the gastric cancer cell line cytotoxicity of citrus extracts. The results of present study might provide a theoretical guidance for the utilization of citrus resources. Full article

(This article belongs to the Collection Bioactive Compounds)

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Quality Control of the Root and Rhizome of Helminthostachys zeylanica (Daodi-Ugon) by HPLC Using Quercetin and Ugonins as Markers

by Kun-Chang Wu^1,†, Chun-Pin Kao^2,†, Yu-Ling Ho^3,* and Yuan-Shiun Chang^1,4,*

¹ Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, College of Chinese Medicine, China Medical University, Taichung 40402, Taiwan

² Department of Nursing, Hsin Sheng Junior College of Medical Care and Management, Taoyuan 32544, Taiwan

³ Department of Nursing, Hungkuang University, Taichung 43302, Taiwan

⁴ Chinese Crude Drug Pharmacy, China Medical University Hospital, Taichung 40402, Taiwan

^† These authors contributed equally to this work.

Molecules 2017, 22(7), 1115; https://doi.org/10.3390/molecules22071115 - 5 Jul 2017

Cited by 15 | Viewed by 5937

Abstract

Daodi-Ugon is the dried root and rhizome of Helminthostachys zeylanica (L.) Hook. and has been used for centuries in the treatment of inflammation, fever, pneumonia, burns, and various disorders. However, the chromatographic methods to determine the phytochemical composition of H. zeylanica have never [...] Read more.

Daodi-Ugon is the dried root and rhizome of Helminthostachys zeylanica (L.) Hook. and has been used for centuries in the treatment of inflammation, fever, pneumonia, burns, and various disorders. However, the chromatographic methods to determine the phytochemical composition of H. zeylanica have never been reported. This study not only aims to develop a valid high-performance liquid chromatography (HPLC) method and to establish a chromatographic fingerprint for the quality control of H. zeylanica, it also establish the proposed content limits of Quercetin, Ugonin J, and Ugonin M. An HPLC method with a RP₁₈ column (250 × 4.6 mm, 5 μm) was developed for the quantitative analysis of Quercetin, Ugonin J, and Ugonin M in H. zeylanica. A simple gradient of (A) methanol/(B) phosphoric acid in water (5–45 min, 70–80% A; 50–55 min, 80–70% A) was used and 360 nm was selected as the detection wavelength. The average contents and proposed content limits for H. zeylanica were calculated with a t-test and a measurement uncertainty test based on 20 batches of authentic H. zeylanica samples. Limits of detection (LOD), quantification (LOQ), linearity, precision, repeatability, stability, and recovery of the developed method were validated. All of the validation results of quantitative determination and fingerprinting methods were satisfactory. The developed method was then applied to assay the contents of Quercetin, Ugonin J, and Ugonin M and to acquire the fingerprints of all of the collected H. zeylanica samples. At the 99% confidence level, the calculated content limits were 56.45, 112.15, and 277.98 mg/kg for Quercetin, Ugonin J, and Ugonin M, respectively. Those validated HPLC quantitative method, fingerprinting profile, and the proposed content limits of three chemical markers that could be used in the quality control of H. zeylanica in the market. Full article

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Open AccessArticle

Characterization of Danaparoid Complex Extractive Drug by an Orthogonal Analytical Approach

by Cristina Gardini¹, Elena Urso², Marco Guerrini², René Van Herpen³, Pauline De Wit³ and Annamaria Naggi^2,*

¹ Centro Alta Tecnologia Istituto di Ricerche Chimiche e Biochimiche G. Ronzoni S.r.l., via G. Colombo 81, 20133 Milan, Italy

² Istituto di Ricerche Chimiche e Biochimiche G. Ronzoni S.r.l., via G. Colombo 81, 20133 Milan, Italy

³ Aspen Oss B.V., Kloosterstraat 6, 5349 AB Oss, The Netherlands

Molecules 2017, 22(7), 1116; https://doi.org/10.3390/molecules22071116 - 5 Jul 2017

Cited by 12 | Viewed by 6294

Abstract

Danaparoid sodium salt, is the active component of ORGARAN, an anticoagulant and antithrombotic drug constituted of three glycosaminoglycans (GAGs) obtained from porcine intestinal mucosa extracts. Heparan sulfate is the major component, dermatan sulfate and chondroitin sulfate being the minor ones. Currently dermatan sulfate [...] Read more.

Danaparoid sodium salt, is the active component of ORGARAN, an anticoagulant and antithrombotic drug constituted of three glycosaminoglycans (GAGs) obtained from porcine intestinal mucosa extracts. Heparan sulfate is the major component, dermatan sulfate and chondroitin sulfate being the minor ones. Currently dermatan sulfate and chondroitin sulfate are quantified by UV detection of their unsaturated disaccharides obtained by enzymatic depolymerization. Due to the complexity of danaparoid biopolymers and the presence of shared components, an orthogonal approach has been applied using more advanced tools and methods. To integrate the analytical profile, 2D heteronuclear single quantum coherence (HSQC) NMR spectroscopy was applied and found effective to identify and quantify GAG component signals as well as those of some process signatures of danaparoid active pharmaceutical ingredient (API) batches. Analyses of components of both API samples and size separated fractions proceeded through the determination and distribution of the molecular weight (Mw) by high performance size exclusion chromatographic triple detector array (HP-SEC-TDA), chain mapping by LC/MS, and mono- (¹H and ¹³C) and bi-dimensional (HSQC) NMR spectroscopy. Finally, large scale chromatographic isolation and depolymerization of each GAG followed by LC/MS and 2D-NMR analysis, allowed the sequences to be defined and components to be evaluated of each GAG including oxidized residues of hexosamines and uronic acids at the reducing ends. Full article

(This article belongs to the Special Issue Looking Forward to the Future of Heparin: New Sources, Developments and Applications)

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Isopentyl-Sulfide-Impregnated Nano-MnO₂ for the Selective Sorption of Pd(II) from the Leaching Liquor of Ores

by Shengjie Wu^†, Mingjin Xie^†, Qin Zhang, Lijiang Zhong, Muhan Chen and Zhangjie Huang^*

¹ School of Chemistry Science and Engineering, Yunnan University, Cuihu North Road No. 2, Kunming 650091, China

^† These two authors contributed equally to this work.

Molecules 2017, 22(7), 1117; https://doi.org/10.3390/molecules22071117 - 6 Jul 2017

Cited by 14 | Viewed by 4400

Abstract

Conventional separation methods are not suitable for recovering palladium present in low concentrations in ore leaching solutions. In this study, a novel isopentyl sulfide (S₂₀₁)-impregnated α-MnO₂ nanorod adsorbent (BISIN) was prepared, characterized, and applied for the selective adsorption and separation [...] Read more.

Conventional separation methods are not suitable for recovering palladium present in low concentrations in ore leaching solutions. In this study, a novel isopentyl sulfide (S₂₀₁)-impregnated α-MnO₂ nanorod adsorbent (BISIN) was prepared, characterized, and applied for the selective adsorption and separation of palladium from the leaching liquor of ores. Batch studies were carried out, and the main adsorption parameters were systematically investigated, in addition to the relevant thermodynamic parameters, isotherms, and kinetic models. The thermodynamic parameters reflected the endothermic and spontaneous nature of the adsorption. Moreover, the experimental results indicated that the Langmuir isotherm model fits the palladium adsorption data well and the adsorption was well described by the pseudo-second-order kinetic model. The main adsorption mechanisms of palladium were elucidated at the molecular level by X-ray crystal structure analysis. Thiourea was found to be an excellent desorption agent, and the palladium-thiourea complex was also confirmed by X-ray crystal structure analysis. The results indicated that almost all of the Pd(II) (>99.0%) is adsorbed on BISIN, whereas less than 2% of the adsorbed Pt(IV), Fe³⁺, Cu²⁺, Ni²⁺, and Co²⁺ is observed under the optimum conditions. The proposed method can be used for the efficient adsorption and separation of palladium from the leaching liquor of ores. Full article

(This article belongs to the Section Organometallic Chemistry)

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Characterization of the Fifth Putative Acetylcholinesterase in the Wolf Spider, Pardosa pseudoannulata

by Xiangkun Meng^1,2, Xixia Xu¹, Haibo Bao¹, Jianjun Wang² and Zewen Liu^1,*

¹ Key Laboratory of Integrated Management of Crop Diseases and Pests (Ministry of Education), College of Plant Protection, Nanjing Agricultural University, Weigang 1, Nanjing 210095, China

² College of Horticulture and Plant Protection, Yangzhou University, Yangzhou 225009, China

Molecules 2017, 22(7), 1118; https://doi.org/10.3390/molecules22071118 - 11 Jul 2017

Cited by 2 | Viewed by 4329

Abstract

Background: Acetylcholinesterase (AChE) is an important neurotransmitter hydrolase in invertebrate and vertebrate nervous systems. The number of AChEs is various among invertebrate species, with different functions including the ‘classical’ role in terminating synaptic transmission and other ‘non-classical’ roles. Methods: Using rapid amplification [...] Read more.

Background: Acetylcholinesterase (AChE) is an important neurotransmitter hydrolase in invertebrate and vertebrate nervous systems. The number of AChEs is various among invertebrate species, with different functions including the ‘classical’ role in terminating synaptic transmission and other ‘non-classical’ roles. Methods: Using rapid amplification of cDNA ends (RACE) technology, a new putative AChE-encoding gene was cloned from Pardosa pseudoannulata, an important predatory natural enemy. Sequence analysis and in vitro expression were employed to determine the structural features and biochemical properties of this putative AChE. Results: The cloned AChE contained the most conserved motifs of AChEs family and was clearly clustered with Arachnida AChEs. Determination of biochemical properties revealed that the recombinant enzyme had the obvious preference for the substrate ATC (acetylthiocholine iodide) versus BTC (butyrylthiocholine iodide). The AChE was highly sensitive to AChE-specific inhibitor BW284C51, but not butyrylcholinesterase-specific inhibitor tetraisopropyl pyrophosphoramide (ISO-OMPA). Based on these results, we concluded that a new AChE was identified from P. pseudoannulata and denoted as PpAChE5. Conclusion: Here we report the identification of a new AChE from P. pseudoannulata and increased the AChE number to five in this species. Although PpAChE5 had the biggest V_max value among five identified AChEs, it showed relatively low affinity with ATC. Similar sensitivity to test insecticides indicated that this AChE might serve as the target for both organophosphorus and carbamate insecticides. Full article

(This article belongs to the Section Medicinal Chemistry)

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Open AccessArticle

Prediction of Drug–Target Interaction Networks from the Integration of Protein Sequences and Drug Chemical Structures

by Fan-Rong Meng¹, Zhu-Hong You^2,*, Xing Chen^3,*, Yong Zhou¹ and Ji-Yong An¹

¹ School of Computer Science and Technology, China University of Mining and Technology, Xuzhou 21116, China

² Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Science, Urumqi 830011, China

³ School of Information and Control Engineering, China University of Mining and Technology, Xuzhou 21116, China

Molecules 2017, 22(7), 1119; https://doi.org/10.3390/molecules22071119 - 5 Jul 2017

Cited by 61 | Viewed by 8327

Abstract

Knowledge of drug–target interaction (DTI) plays an important role in discovering new drug candidates. Unfortunately, there are unavoidable shortcomings; including the time-consuming and expensive nature of the experimental method to predict DTI. Therefore, it motivates us to develop an effective computational method to [...] Read more.

Knowledge of drug–target interaction (DTI) plays an important role in discovering new drug candidates. Unfortunately, there are unavoidable shortcomings; including the time-consuming and expensive nature of the experimental method to predict DTI. Therefore, it motivates us to develop an effective computational method to predict DTI based on protein sequence. In the paper, we proposed a novel computational approach based on protein sequence, namely PDTPS (Predicting Drug Targets with Protein Sequence) to predict DTI. The PDTPS method combines Bi-gram probabilities (BIGP), Position Specific Scoring Matrix (PSSM), and Principal Component Analysis (PCA) with Relevance Vector Machine (RVM). In order to evaluate the prediction capacity of the PDTPS, the experiment was carried out on enzyme, ion channel, GPCR, and nuclear receptor datasets by using five-fold cross-validation tests. The proposed PDTPS method achieved average accuracy of 97.73%, 93.12%, 86.78%, and 87.78% on enzyme, ion channel, GPCR and nuclear receptor datasets, respectively. The experimental results showed that our method has good prediction performance. Furthermore, in order to further evaluate the prediction performance of the proposed PDTPS method, we compared it with the state-of-the-art support vector machine (SVM) classifier on enzyme and ion channel datasets, and other exiting methods on four datasets. The promising comparison results further demonstrate that the efficiency and robust of the proposed PDTPS method. This makes it a useful tool and suitable for predicting DTI, as well as other bioinformatics tasks. Full article

(This article belongs to the Special Issue Computational Analysis for Protein Structure and Interaction)

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Open AccessArticle

Advantages of an Electrochemical Method Compared to the Spectrophotometric Kinetic Study of Peroxidase Inhibition by Boroxine Derivative

by Jelena Ostojić^1,*

, Safija Herenda¹, Zerina Bešić¹, Mladen Miloš² and Borivoj Galić¹

¹ Department of Chemistry, Faculty of Science, University of Sarajevo, Zmaja od Bosne 33-35, 71 000 Sarajevo, Bosnia and Herzegovina

² Faculty of Chemistry and Technology, University of Split, Teslina 10, 21 000 Split, Croatia

Molecules 2017, 22(7), 1120; https://doi.org/10.3390/molecules22071120 - 5 Jul 2017

Cited by 48 | Viewed by 5211

Abstract

In this study, boroxine derivative (K₂[B₃O₃F₄OH]) was tested as an inhibitor of horseradish peroxidase (HRP) by spectrophotometric and electrochemical methods. The activity of horseradish peroxidase was first studied under steady-state kinetic conditions by a spectrophotometric [...] Read more.

In this study, boroxine derivative (K₂[B₃O₃F₄OH]) was tested as an inhibitor of horseradish peroxidase (HRP) by spectrophotometric and electrochemical methods. The activity of horseradish peroxidase was first studied under steady-state kinetic conditions by a spectrophotometric method which required the use of guaiacol as a second substrate to measure guaiacol peroxidation. The results of this method have shown that, by changing the concentration of guaiacol as the literature suggests, a different type of inhibition is observed than when changing the concentration of hydrogen peroxide as the substrate. This suggests that guaiacol interferes with the reaction in some way. The electrochemical method involves direct electron transfer of HRP immobilized in Nafion nanocomposite films on a glassy carbon (GC) electrode, creating a sensor with an electro-catalytic response to the reduction of hydrogen peroxide. The electrochemical method simplifies kinetic assays by removing the requirement of reducing substrates. Full article

(This article belongs to the Special Issue Metallopeptides)

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Open AccessArticle

Anti-Inflammatory and Anti-Urolithiasis Effects of Polyphenolic Compounds from Quercus gilva Blume

by Sung Hye Youn¹, Joo Hee Kwon¹, Jun Yin¹, Le Thi Tam¹, Hye Shin Ahn¹, Soon Chul Myung² and Min Won Lee^1,*

¹ Laboratory of Pharmacognosy and Natural Product Derived Medicine, College of Pharmacy, Chung-Ang University, Seoul 156-756, Korea

² Department of Urology, College of Medicine, Chung-Ang University, Seoul 156-756, Korea

Molecules 2017, 22(7), 1121; https://doi.org/10.3390/molecules22071121 - 5 Jul 2017

Cited by 16 | Viewed by 7510

Abstract

Quercus gilva Bume (QGB, family Fagaceae) is a tall evergreen oak species tree that grows in warm temperate regions in Korea, Japan, China and Taiwan. Quercus plants have long been the basis of traditional medicines. Their clinical benefits according to traditional medicine include [...] Read more.

Quercus gilva Bume (QGB, family Fagaceae) is a tall evergreen oak species tree that grows in warm temperate regions in Korea, Japan, China and Taiwan. Quercus plants have long been the basis of traditional medicines. Their clinical benefits according to traditional medicine include relief of urolithiasis, tremors and inflammation. In the present study, the anti-urolithiasis activity including anti-inflammatory and anti-oxidative activities, of some phenolic compounds isolated from QGB were described. Seven compounds were isolated and identified as picraquassioside D (1), quercussioside (2), (+)-lyoniresinol-9′α-O-β-d-xylopyranoside (3), (+)-catechin (4), (−)-epicatechin (5), procyanidin B-3 (6), and procyanidin B-4 (7). Compounds 5–7 showed potent anti-oxidative and anti-inflammatory activities. These compounds were further tested for their inhibition of the gene expression of the inflammatory cytokines. The three compounds 5–7 showed dose-dependent inhibitory activities on gene expression of COX-2 and IL-1β. In vivo, urolithiasis was induced more effectively in an animal model of acute urolithiasis by the administration of QGB extract. These results indicate the potential of compounds from QGB in the treatment of urolithiasis. Full article

(This article belongs to the Collection Bioactive Compounds)

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Open AccessArticle

Protective Effect of Quercetin against Oxidative Stress-Induced Cytotoxicity in Rat Pheochromocytoma (PC-12) Cells

by Dengke Bao¹, Jingkai Wang², Xiaobin Pang¹ and Hongliang Liu^1,*

¹ Institute of Pharmacy, Pharmaceutical College of Henan University, Kaifeng 475004, China

² Department of Nursing, NanYang Medical College, NanYang 473000, China

Molecules 2017, 22(7), 1122; https://doi.org/10.3390/molecules22071122 - 6 Jul 2017

Cited by 95 | Viewed by 7869

Abstract

Oxidative stress has been implicated in the pathogenesis of many kinds of neurodegenerative disorders, particularly Parkinson’s disease. Quercetin is a bioflavonoid found ubiquitously in fruits and vegetables, and has antioxidative activity. However, the underlying mechanism of the antioxidative effect of quercetin in neurodegenerative [...] Read more.

Oxidative stress has been implicated in the pathogenesis of many kinds of neurodegenerative disorders, particularly Parkinson’s disease. Quercetin is a bioflavonoid found ubiquitously in fruits and vegetables, and has antioxidative activity. However, the underlying mechanism of the antioxidative effect of quercetin in neurodegenerative diseases has not been well explored. Here, we investigated the antioxidative effect and underlying molecular mechanisms of quercetin on PC-12 cells. We found that PC-12 cells pretreated with quercetin exhibited an increased cell viability and reduced lactate dehydrogenase (LDH) release when exposed to hydrogen peroxide (H₂O₂). The significantly-alleviated intracellular reactive oxygen species (ROS), malondialdehyde (MDA), and lipoperoxidation of the cell membrane of PC-12 cells induced by H₂O₂ were observed in the quercetin pretreated group. Furthermore, quercetin pretreatment markedly reduced the apoptosis of PC-12 cells and hippocampal neurons. The inductions of antioxidant enzyme catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) in PC-12 cells exposed to H₂O₂ were significantly reduced by preatment with quercetin. In addition, quercetin pretreatment significantly increased Bcl-2 expression, and reduced Bax, cleaved caspase-3 and p53 expressions. In conclusion, this study demonstrated that quercetin exhibited a protective effect against oxidative stress-induced apoptosis in PC-12 cells. Our findings suggested that quercetin may be developed as a novel therapeutic agent for neurodegenerative diseases induced by oxidative stress. Full article

(This article belongs to the Special Issue Natural Products and Chronic Diseases)

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Open AccessArticle

A Purified Serine Protease from Nereis virens and Its Impaction of Apoptosis on Human Lung Cancer Cells

by Yunping Tang^1,†

, Fangmiao Yu^1,†, Guomei Zhang¹, Zuisu Yang¹, Fangfang Huang¹ and Guofang Ding^1,2,*

¹ School of Food and Pharmacy, Zhejiang Provincial Engineering Technology Research Center of Marine Biomedical Products, Zhejiang Ocean University, 1st Haidanan Road, Changzhi Island, Lincheng, Zhoushan 316022, China

² Zhejiang Marine Fisheries Research Institution, Zhoushan 316021, China

^† These authors contributed equally to this paper.

Molecules 2017, 22(7), 1123; https://doi.org/10.3390/molecules22071123 - 7 Jul 2017

Cited by 18 | Viewed by 4726

Abstract

Nereis active protease (NAP) is a novel fibrinolytic active serine protease from the polychaete Nereis virens. In this study, NAP was purified from Nereis virens and the effects of NAP on human lung cancer cells were investigated. Our results indicated that NAP [...] Read more.

Nereis active protease (NAP) is a novel fibrinolytic active serine protease from the polychaete Nereis virens. In this study, NAP was purified from Nereis virens and the effects of NAP on human lung cancer cells were investigated. Our results indicated that NAP inhibited the proliferation and induced apoptosis of H1299 cells in a time- and dose-dependent manner. The loss of mitochondrial membrane potential, the activation of Bax and cleaved-caspase 3/9, the release of cytochrome C, and the suppression of Bcl-2 and poly-ADP ribose polymerase were observed in NAP-treated H1299 cells by flow cytometry and Western blotting. Moreover, the expression levels of Bax and Bcl-2 mRNA were determined by real-time quantitative polymerase chain reaction and the Bax/Bcl-2 expression ratio was increased in the NAP-treated cell lines. The results indicated that NAP-induced apoptosis may be related to mitochondria mediated apoptosis and occurs through caspase-dependent pathways. Then, the effects of NAP on tumor growth in animal models were observed, where 5 or 10 mg/kg of NAP noticeably reduced tumor volume and weight and increased apoptosis as determined by Western blotting when compared to the negative control group. Therefore, our findings suggest that NAP could be a hopeful anticancer medicine for its propensity to inhibit growth and induce of apoptosis in human lung cancer cells. Full article

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Open AccessArticle

Substituted Caffeic and Ferulic Acid Phenethyl Esters: Synthesis, Leukotrienes Biosynthesis Inhibition, and Cytotoxic Activity

by Pier Morin, Patrick-Denis St-Coeur, Jérémie A. Doiron, Marc Cormier, Julie J. Poitras, Marc E. Surette and Mohamed Touaibia^*

Department of Chemistry and Biochemistry, Université de Moncton, Moncton, NB E1A 3E9, Canada

Molecules 2017, 22(7), 1124; https://doi.org/10.3390/molecules22071124 - 6 Jul 2017

Cited by 17 | Viewed by 6265

Abstract

Glioblastoma multiforme (GBM) is an aggressive brain tumor that correlates with short patient survival and for which therapeutic options are limited. Polyphenolic compounds, including caffeic acid phenethyl ester (CAPE, 1a), have been investigated for their anticancer properties in several types of cancer. [...] Read more.

Glioblastoma multiforme (GBM) is an aggressive brain tumor that correlates with short patient survival and for which therapeutic options are limited. Polyphenolic compounds, including caffeic acid phenethyl ester (CAPE, 1a), have been investigated for their anticancer properties in several types of cancer. To further explore these properties in brain cancer cells, a series of caffeic and ferulic acid esters bearing additional oxygens moieties (OH or OCH₃) were designed and synthesized. (CAPE, 1a), but not ferulic acid phenethyl ester (FAPE, 1b), displayed substantial cytotoxicity against two glioma cell lines. Some but not all selected compounds derived from both (CAPE, 1a) and (FAPE, 1b) also displayed cytotoxicity. All CAPE-derived compounds were able to significantly inhibit 5-lipoxygenase (5-LO), however FAPE-derived compounds were largely ineffective 5-LO inhibitors. Molecular docking revealed new hydrogen bonds and π-π interactions between the enzyme and some of the investigated compounds. Overall, this work highlights the relevance of exploring polyphenolic compounds in cancer models and provides additional leads in the development of novel therapeutic strategies in gliomas. Full article

(This article belongs to the Section Medicinal Chemistry)

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Open AccessArticle

Measuring the Transition Rates of Coalescence Events during Double Phase Separation in Microgravity

by Ana Oprisan^1,*

, Yves Garrabos², Carole Lecoutre² and Daniel Beysens³

¹ Department of Physics and Astronomy, College of Charleston, Charleston, SC 29424, USA

² CNRS, Institut de Chimie de la Matière Condensée de Bordeaux, ESEME, Université de Bordeaux, UPR 9048, F-33600 Pessac, France

³ Physique et Mécanique des Milieux Hétérogènes, UMR 7636 CNRS-ESPCI-Université Pierre et Marie Curie - Université Paris Diderot, 10 rue Vauquelin, 75005 Paris, France

Molecules 2017, 22(7), 1125; https://doi.org/10.3390/molecules22071125 - 6 Jul 2017

Cited by 9 | Viewed by 4179

Abstract

Phase transition is a ubiquitous phenomenon in nature, science and technology. In general, the phase separation from a homogeneous phase depends on the depth of the temperature quench into the two-phase region. Earth’s gravity masks the details of phase separation phenomena, which is [...] Read more.

Phase transition is a ubiquitous phenomenon in nature, science and technology. In general, the phase separation from a homogeneous phase depends on the depth of the temperature quench into the two-phase region. Earth’s gravity masks the details of phase separation phenomena, which is why experiments were performed under weightlessness. Under such conditions, the pure fluid sulphur hexafluoride (SF

_{6}

) near its critical point also benefits from the universality of phase separation behavior and critical slowing down of dynamics. Initially, the fluid was slightly below its critical temperature with the liquid matrix separated from the vapor phase. A 0.2 mK temperature quench further cooled down the fluid and produced a double phase separation with liquid droplets inside the vapor phase and vapor bubbles inside the liquid matrix, respectively. The liquid droplets and the vapor bubbles respective distributions were well fitted by a lognormal function. The evolution of discrete bins of different radii allowed the derivation of the transition rates for coalescence processes. Based on the largest transition rates, two main coalescence mechanisms were identified: (1) asymmetric coalescences between one small droplet of about 20

μ

m and a wide range of larger droplets; and (2) symmetric coalescences between droplets of large and similar radii. Both mechanisms lead to a continuous decline of the fraction of small radii droplets and an increase in the fraction of the large radii droplets. Similar coalescence mechanisms were observed for vapor bubbles. However, the mean radii of liquid droplets exhibits a

t^{1 / 3}

evolution, whereas the mean radii of the vapor bubbles exhibit a

t^{1 / 2}

evolution. Full article

(This article belongs to the Special Issue Sub- and Supercritical Fluids and Green Chemistry)

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Open AccessArticle

Design, Synthesis and Bioactivities of Novel 1,4-Pentadien-3-one Derivatives Containing a Substituted Pyrazolyl Moiety

by Cuili Chen^1,2, Jia Chen³, Haiying Gu^1,2,*, Ning Bao² and Hong Dai^3,*

¹ College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215123, China

² School of Public Health, Nantong University, Nantong 226019, China

³ College of Chemistry and Chemical Engineering, Nantong University, Nantong 226019, China

Molecules 2017, 22(7), 1126; https://doi.org/10.3390/molecules22071126 - 6 Jul 2017

Cited by 5 | Viewed by 3721

Abstract

In this study, in order to find novel biologically active penta-1,4-dien-3-one derivatives, a series of penta-1,4-dien-3-one compounds containing a substituted pyrazole subunit were designed and synthesized. Their structures were characterized by ¹H-NMR, ¹³C-NMR and elemental analysis. The preliminary bioassays displayed that [...] Read more.

In this study, in order to find novel biologically active penta-1,4-dien-3-one derivatives, a series of penta-1,4-dien-3-one compounds containing a substituted pyrazole subunit were designed and synthesized. Their structures were characterized by ¹H-NMR, ¹³C-NMR and elemental analysis. The preliminary bioassays displayed that most of the title compounds showed significant antiproliferative activity against HepG2 cell lines. Especially, compounds 7a–m, o, r, s, u, w, y and z were active against HepG2 cells with IC₅₀ values of 0.10–5.05 μM, which were superior to that of the contrast sorafenib (IC₅₀ = 16.20 μM). Full article

(This article belongs to the Section Organic Chemistry)

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Open AccessEditorial

Special Issue: Frontiers in Antimicrobial Drug Discovery and Design

by Daniela Barlocco^* and Fiorella Meneghetti^*

Department of Pharmaceutical Sciences (DISFARM), University of Milan, 20133 Milano, Italy

Molecules 2017, 22(7), 1127; https://doi.org/10.3390/molecules22071127 - 6 Jul 2017

Cited by 2 | Viewed by 3433

Abstract

Since the discovery of Penicillin, antibiotics have saved millions of lives every year.[...] Full article

(This article belongs to the Special Issue Frontiers in Antimicrobial Drug Discovery and Design)

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Open AccessArticle

DeCAF—Discrimination, Comparison, Alignment Tool for 2D PHarmacophores

by Marta M. Stepniewska-Dziubinska¹

, Piotr Zielenkiewicz^1,2 and Pawel Siedlecki^1,2,*

¹ Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawinskiego 5a, 02-106 Warsaw, Poland

² Department of Systems Biology, Institute of Experimental Plant Biology and Biotechnology, University of Warsaw, Miecznikowa 1, 02-096 Warsaw, Poland

Molecules 2017, 22(7), 1128; https://doi.org/10.3390/molecules22071128 - 6 Jul 2017

Cited by 6 | Viewed by 5630

Abstract

Comparison of small molecules is a common component of many cheminformatics workflows, including the design of new compounds and libraries as well as side-effect predictions and drug repurposing. Currently, large-scale comparison methods rely mostly on simple fingerprint representation of molecules, which take into [...] Read more.

Comparison of small molecules is a common component of many cheminformatics workflows, including the design of new compounds and libraries as well as side-effect predictions and drug repurposing. Currently, large-scale comparison methods rely mostly on simple fingerprint representation of molecules, which take into account the structural similarities of compounds. Methods that utilize 3D information depend on multiple conformer generation steps, which are computationally expensive and can greatly influence their results. The aim of this study was to augment molecule representation with spatial and physicochemical properties while simultaneously avoiding conformer generation. To achieve this goal, we describe a molecule as an undirected graph in which the nodes correspond to atoms with pharmacophoric properties and the edges of the graph represent the distances between features. This approach combines the benefits of a conformation-free representation of a molecule with additional spatial information. We implemented our approach as an open-source Python module called DeCAF (Discrimination, Comparison, Alignment tool for 2D PHarmacophores), freely available at http://bitbucket.org/marta-sd/decaf. We show DeCAF’s strengths and weaknesses with usage examples and thorough statistical evaluation. Additionally, we show that our method can be manually tweaked to further improve the results for specific tasks. The full dataset on which DeCAF was evaluated and all scripts used to calculate and analyze the results are also provided. Full article

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Open AccessArticle

Steroid Alkaloids from Holarrhena africana with Strong Activity against Trypanosoma brucei rhodesiense

by Charles Okeke Nnadi^1,2

, Ngozi Justina Nwodo², Marcel Kaiser^3,4

, Reto Brun^3,4 and Thomas J. Schmidt^1,*

¹ Institute of Pharmaceutical Biology and Phytochemistry (IPBP), University of Münster, PharmaCampus Corrensstraße 48, D-48149 Münster, Germany

² Department of Pharmaceutical and Medicinal Chemistry, Faculty of Pharmaceutical Sciences, University of Nigeria Nsukka, Enugu State 410001, Nigeria

³ Swiss Tropical and Public Health Institute (Swiss TPH), Socinstr. 57, CH-4051 Basel, Switzerland

⁴ University of Basel, Petersplatz 1, CH-4003 Basel, Switzerland

Molecules 2017, 22(7), 1129; https://doi.org/10.3390/molecules22071129 - 6 Jul 2017

Cited by 35 | Viewed by 6931

Abstract

In our continued search for natural compounds with activity against Trypanosoma brucei, causative agent of human African trypanosomiasis (HAT, “sleeping sickness”), we have investigated extracts from the leaves and bark of the West African Holarrhena africana (syn. Holarrhena floribunda; Apocynaceae). The [...] Read more.

In our continued search for natural compounds with activity against Trypanosoma brucei, causative agent of human African trypanosomiasis (HAT, “sleeping sickness”), we have investigated extracts from the leaves and bark of the West African Holarrhena africana (syn. Holarrhena floribunda; Apocynaceae). The extracts and their alkaloid-enriched fractions displayed promising in vitro activity against bloodstream forms of T. brucei rhodesiense (Tbr; East African HAT). Bioactivity-guided chromatographic fractionation of the alkaloid-rich fractions resulted in the isolation of 17 steroid alkaloids, one nitrogen-free steroid and one alkaloid-like non-steroid. Impressive activities (IC₅₀ in µM) against Tbr were recorded for 3β-holaphyllamine (0.40 ± 0.28), 3α-holaphyllamine (0.37 ± 0.16), 3β-dihydroholaphyllamine (0.67 ± 0.03), N-methylholaphyllamine (0.08 ± 0.01), conessimine (0.17 ± 0.08), conessine (0.42 ± 0.09), isoconessimine (0.17 ± 0.11) and holarrhesine (0.12 ± 0.08) with selectivity indices ranging from 13 to 302. Based on comparison of the structures of this congeneric series of steroid alkaloids and their activities, structure-activity relationships (SARs) could be established. It was found that a basic amino group at position C-3 of the pregnane or pregn-5-ene steroid nucleus is required for a significant anti-trypanosomal activity. The mono-methylated amino group at C-3 represents an optimum for activity. ∆^5,6 unsaturation slightly increased the activity while hydrolysis of C-12β ester derivatives led to a loss of activity. An additional amino group at C-20 engaged in a pyrrolidine ring closed towards C-18 significantly increased the selectivity index of the compounds. Our findings provide useful empirical data for further development of steroid alkaloids as a novel class of anti-trypanosomal compounds which represent a promising starting point towards new drugs to combat human African trypanosomiasis. Full article

(This article belongs to the Collection Natural Products as Leads or Drugs against Neglected Tropical Diseases)

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Open AccessArticle

Trifluoroethoxy-Coated Phthalocyanine Catalyzes Perfluoroalkylation of Alkenes under Visible-Light Irradiation

by Kohei Matsuzaki¹, Tomoya Hiromura², Hideki Amii³ and Norio Shibata^1,2,*

¹ Department of Nanopharmaceutical Sciences, Nagoya Institute of Technology Gokiso, Showa-ku, Nagoya 466-8555, Japan

² Department of Life Science and Applied Chemistry, Nagoya Institute of Technology Gokiso, Showa-ku, Nagoya 466-8555, Japan

³ Division of Molecular Science, Graduate School of Science and Technology, Gunma University, 1-5-1 Tenjin-cho, Kiryu, Gunma 376-8515, Japan

Molecules 2017, 22(7), 1130; https://doi.org/10.3390/molecules22071130 - 7 Jul 2017

Cited by 18 | Viewed by 5383

Abstract

We disclose herein the perfluoroalkylation of alkenes catalyzed by trifluoroethoxy-coated zinc phthalocyanine under irradiation of visible light. Perfluoroalkyl iodides were nicely incorporated into unsaturated substrates, including alkyne, to provide perfluoroalkyl and iodide adducts in moderate to good yields. Trifluoromethylation is also possible by [...] Read more.

We disclose herein the perfluoroalkylation of alkenes catalyzed by trifluoroethoxy-coated zinc phthalocyanine under irradiation of visible light. Perfluoroalkyl iodides were nicely incorporated into unsaturated substrates, including alkyne, to provide perfluoroalkyl and iodide adducts in moderate to good yields. Trifluoromethylation is also possible by trifluoromethyl iodide under the same reaction conditions. The mechanistic study is discussed. Full article

(This article belongs to the Special Issue Tri- and Di-Fluoromethylation and Tri- and Di-Fluoromethylchalcogenation Reactions)

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Open AccessArticle

[3+2] Cycloaddition of Tosylmethyl Isocyanide with Styrylisoxazoles: Facile Access to Polysubstituted 3-(Isoxazol-5-yl)pyrroles

by Xueming Zhang¹, Xianxiu Xu² and Dawei Zhang^1,*

¹ College of Chemistry, Jilin University, Changchun 130012, China

² College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong Normal University, Jinan 250014, China

Molecules 2017, 22(7), 1131; https://doi.org/10.3390/molecules22071131 - 7 Jul 2017

Cited by 8 | Viewed by 4740

Abstract

A facile access to polysubstituted 3-(isoxazol-5-yl)pyrroles was developed through [3+2] cycloaddition of tosylmethyl isocyanide (TosMIC) and styrylisoxazoles. In the presence of KOH, various styrylisoxazoles reacted smoothly with tosylmethyl isocyanide and analogs to deliver a wide range of 3-(isoxazol-5-yl)pyrroles at ambient temperature. This transformation [...] Read more.

A facile access to polysubstituted 3-(isoxazol-5-yl)pyrroles was developed through [3+2] cycloaddition of tosylmethyl isocyanide (TosMIC) and styrylisoxazoles. In the presence of KOH, various styrylisoxazoles reacted smoothly with tosylmethyl isocyanide and analogs to deliver a wide range of 3-(isoxazol-5-yl)pyrroles at ambient temperature. This transformation is operationally simple, high-yielding, and displays broad substrate scope. Full article

(This article belongs to the Special Issue Isocyanide)

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Open AccessArticle

Novel N-Arylaminophosphonates Bearing a Pyrrole Moiety and Their Ecotoxicological Properties

by Jarosław Lewkowski^1,*, Marta Morawska¹, Anna Kaczmarek^1,3, Diana Rogacz² and Piotr Rychter^2,*

¹ Department of Organic Chemistry, Faculty of Chemistry, University of Łódź, Tamka 12, 91-403 Łódź, Poland

² Faculty of Mathematics and Natural Science, Jan Długosz University in Częstochowa, 13/15 Armii Krajowej Av., 42-200 Częstochowa, Poland

³ M.Sc. Student at the Faculty of Chemistry, University of Łódź, Tamka 12, 91-403 Łódź, Poland

Molecules 2017, 22(7), 1132; https://doi.org/10.3390/molecules22071132 - 7 Jul 2017

Cited by 3 | Viewed by 3785

Abstract

A wide range of biological activities of aminophosphonates predisposes them to find applications as anticancer, antiviral, antimicrobial, antifungal, or herbicidal agents. Despite a number of positive aspects of the use of aminophosphonates, their applications may cause a risk to the environment, which is [...] Read more.

A wide range of biological activities of aminophosphonates predisposes them to find applications as anticancer, antiviral, antimicrobial, antifungal, or herbicidal agents. Despite a number of positive aspects of the use of aminophosphonates, their applications may cause a risk to the environment, which is well exemplified by the case of glyphosate. Therefore, scientists see a pressing need to rate ecotoxicity of aminophosphonates. Nowadays, it is recommended to use comprehensive tools to carry out appropriate and effective risk assessments of toxic substances. For these purposes, tests based on the acute toxicity of the luminescent bacteria Aliivibrio fischeri, as well as the measurement of sub-chronic toxicity of the crustacean Heterocypris incongruens seem to be the most convenient. A series of five diphenyl N-arylamino(pyrrole-2-yl)methylphosphonates was synthesized and preliminary evaluation of their ecotoxicological properties was performed. In order to carry out such investigations, we applied the two biotests mentioned above. Results showed that the N-(4-nitrophenyl) derivative was the most toxic for bacteria in comparison to other tested compounds. As for crustaceans, N-phenyl and N-naphthyl derivatives were found to be the most harmful, simultaneously being relatively harmless for bacteria. Such a phenomenon are discussed in correlation with the literature, while its reason is discussed with respect to the aspect of structure of the tested compounds. Full article

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Open AccessArticle

Coinage Metal Complexes of the Carbenic Tautomer of a Conjugated Mesomeric Betaine Akin to Nitron

by Charlotte Thie, Clemens Bruhn, Michael Leibold and Ulrich Siemeling^*

Institute of Chemistry, University of Kassel, Heinrich-Plett-Straße 40, 34132 Kassel, Germany

Molecules 2017, 22(7), 1133; https://doi.org/10.3390/molecules22071133 - 7 Jul 2017

Cited by 14 | Viewed by 6987

Abstract

This study was motivated by our recent observation that the analytical reagent Nitron (2) is an “instant carbene”, whose reaction with coinage metal salts MX afforded complexes of its carbenic tautomer 1,4-diphenyl-3-phenylamino-1,2,4-triazol-5-ylidene (2′). Our aim was to establish an [...] Read more.

This study was motivated by our recent observation that the analytical reagent Nitron (2) is an “instant carbene”, whose reaction with coinage metal salts MX afforded complexes of its carbenic tautomer 1,4-diphenyl-3-phenylamino-1,2,4-triazol-5-ylidene (2′). Our aim was to establish an alkyl homologue of 2 in order to achieve a carbenic tautomer of higher donicity. For this purpose 1-tert-butyl-4-methyl-1,2,4-triazol-4-ium-3-tert-butylaminide (6) was synthesized. Its reactions with MX afforded complexes of the carbenic tautomer 1-tert-butyl-3-tert-butylamino-4-methyl-1,2,4-triazol-5-ylidene (6′). With a stoichiometric ratio of 1:1 complexes of the type [MX(6′)] were obtained. A ratio of 2:1 furnished complexes of the type [MX(6′)₂] or [M(6′)₂]X. 6′ is a better σ-donor and less electrophilic than 2′ according to NMR spectroscopic data of 6H[BF₄] and 6′ = Se, respectively, and IR spectroscopic data of [RhCl(6′)(CO)₂] confirm that its net electron donor capacity is superior to that of 2′. A comparison of the complexes of 2′ and 6′ reveals two pronounced structural differences. [CuX(6′)₂] (X = Cl, Br) exhibit more acute C‒Cu‒C bond angles than [CuX(2′)₂]. In contrast to [CuCl(2′)], [CuCl(6′)] aggregates through Cu···Cu contacts of ca. 2.87 Å, compatible with cuprophilic interactions. These differences may be explained by the complementary steric requirements of the t-Bu and the Me substituent of 6′. Full article

(This article belongs to the Special Issue Group 11 Metal Complexes with N-Heterocyclic Carbene Ligands: Recent Developments)

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Open AccessArticle

Current Study of the Mechanism of Action of the Potential Anti-Epileptic Agent Q808

by Xiang Li¹, Hong-Jian Zhang², Qing Wang³, Dian-Wen Zhang³, Di Wu³, Wei Li^3,* and Zhe-Shan Quan²

¹ Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, College of Life Sciences, Jilin University, No. 2699 Qianjin Street, Changchun 130012, China

² Key Laboratory of Natural Resources and Functional Molecules of the Changbai Mountain, Affiliated Ministry of Education, College of Pharmacy, Yanbian University, Yanji 133002, China

³ Academy of Chinese Medical Sciences of Jilin Province, Changchun 130012, China

Molecules 2017, 22(7), 1134; https://doi.org/10.3390/molecules22071134 - 7 Jul 2017

Cited by 8 | Viewed by 3655

Abstract

Our previous study showed that the anticonvulsant Q808 might be effective against seizures induced by maximal electroshock, pentylenetetrazole (PTZ), isoniazid (ISO), thiosemicarbazide (THIO), and 3-mercaptopropionic acid (3-MP). In the present study, we explored the possible mechanism of action of Q808. Results obtained with [...] Read more.

Our previous study showed that the anticonvulsant Q808 might be effective against seizures induced by maximal electroshock, pentylenetetrazole (PTZ), isoniazid (ISO), thiosemicarbazide (THIO), and 3-mercaptopropionic acid (3-MP). In the present study, we explored the possible mechanism of action of Q808. Results obtained with high-performance liquid chromatography (HPLC) suggest that Q808 may affect neurotransmitter content in the brain, by specifically increasing GABA content in the rat hippocampus at doses of 40 mg/kg and 80 mg/kg, and by reducing the content of glutamate and glutamine in the rat thalamus at a dose of 80 mg/kg. Intriguingly, there were no changes in the neurotransmitter content in the cortex in response to Q808. In vitro brain slice electrophysiological studies showed that 10⁻⁵ M Q808 enhanced the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) in corn cells of the CA1 area of the hippocampus, and had no effect on the amplitude of sIPSCs, the frequency and amplitude of spontaneous excitatory postsynaptic currents (sEPSCs), or γ-aminobutyric acid (GABA) receptor-mediated currents in primary cultured hippocampal neurons. These findings suggest that the antiepileptic activity of Q808 may be due to its ability to increase the amount of GABA between synapses, without affecting the function of GABA receptors. Full article

(This article belongs to the Section Medicinal Chemistry)

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Open AccessReview

How Can Synergism of Traditional Medicines Benefit from Network Pharmacology?

by Haidan Yuan^1,2, Qianqian Ma¹, Heying Cui³, Guancheng Liu¹, Xiaoyan Zhao¹, Wei Li¹ and Guangchun Piao^1,2,*

¹ College of Pharmacy, Yanbian University; 977 Gongyuan Street, Yanji 133002, China

² Key Laboratory of Natural Resources of Changbai Mountain & Functional Molecules, Yanbian University, Ministry of Education, Yanji 133002, China

³ College of Traditional Chinese Medicine, Yanbian University; Yanji 133002, China

Molecules 2017, 22(7), 1135; https://doi.org/10.3390/molecules22071135 - 7 Jul 2017

Cited by 324 | Viewed by 15673

Abstract

Abstract: Many prescriptions of traditional medicines (TMs), whose efficacy has been tested in clinical practice, have great therapeutic value and represent an excellent resource for drug discovery. Research into single compounds of TMs, such as artemisinin from Artemisia annua L., has achieved great [...] Read more.

Abstract: Many prescriptions of traditional medicines (TMs), whose efficacy has been tested in clinical practice, have great therapeutic value and represent an excellent resource for drug discovery. Research into single compounds of TMs, such as artemisinin from Artemisia annua L., has achieved great success; however, it has become evident that a TM prescription (which frequently contains various herbs or other components) has a synergistic effect in effecting a cure or reducing toxicity. Network pharmacology targets biological networks and analyzes the links among drugs, targets, and diseases in those networks. Comprehensive, systematic research into network pharmacology is consistent with the perspective of holisticity, which is a main characteristic of many TMs. By means of network pharmacology, research has demonstrated that many a TM show a synergistic effect by acting at different levels on multiple targets and pathways. This approach effectively bridges the gap between modern medicine and TM, and it greatly facilitates studies into the synergistic actions of TMs. There are different kinds of synergistic effects with TMs, such as synergy among herbs, effective parts, and pure compounds; however, for various reasons, new drug discovery should at present focus on synergy among pure compounds. Full article

(This article belongs to the Section Natural Products Chemistry)

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Open AccessArticle

Cytotoxic Compounds from Aloe megalacantha

by Negera Abdissa^1,2,*, Sebastian Gohlke¹, Marcel Frese¹ and Norbert Sewald^1,*

¹ Department of Chemistry, Organic and Bioorganic Chemistry, Bielefeld University, P.O. Box 100131, 33501 Bielefeld, Germany

² Department of Chemistry, College of Natural Sciences, Jimma University, P.O. Box 378, 251 Jimma, Ethiopia

Molecules 2017, 22(7), 1136; https://doi.org/10.3390/molecules22071136 - 7 Jul 2017

Cited by 17 | Viewed by 5569

Abstract

Phytochemical investigation of the ethyl acetate extract of the roots of Aloe megalacantha led to the isolation of four new natural products—1,8-dimethoxynepodinol (1), aloesaponarin III (2), 10-O-methylchrysalodin (3) and methyl-26-O-feruloyl-oxyhexacosanate (4)—along [...] Read more.

Phytochemical investigation of the ethyl acetate extract of the roots of Aloe megalacantha led to the isolation of four new natural products—1,8-dimethoxynepodinol (1), aloesaponarin III (2), 10-O-methylchrysalodin (3) and methyl-26-O-feruloyl-oxyhexacosanate (4)—along with ten known compounds. All purified metabolites were characterized by NMR, mass spectrometric analyses and comparison with literature data. The isolates were evaluated for their cytotoxic activity against a human cervix carcinoma cell line KB-3-1 and some of them exhibited good activity, with aloesaponarin II (IC₅₀ = 0.98 µM) being the most active compound. Full article

(This article belongs to the Collection Bioactive Compounds)

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Open AccessReview

Analytical Techniques and Pharmacokinetics of Gastrodia elata Blume and Its Constituents

by Jinyi Wu, Bingchu Wu, Chunlan Tang^* and Jinshun Zhao^*

Department of Preventative Medicine, Zhejiang Provincial Key Laboratory of Pathological and Physiological Technology, Medical School of Ningbo University, Ningbo 315211, Zhejiang, China

Molecules 2017, 22(7), 1137; https://doi.org/10.3390/molecules22071137 - 8 Jul 2017

Cited by 40 | Viewed by 6970

Abstract

Gastrodia elata Blume (G. elata), commonly called Tianma in Chinese, is an important and notable traditional Chinese medicine (TCM), which has been used in China as an anticonvulsant, analgesic, sedative, anti-asthma, anti-immune drug since ancient times. The aim of this review [...] Read more.

Gastrodia elata Blume (G. elata), commonly called Tianma in Chinese, is an important and notable traditional Chinese medicine (TCM), which has been used in China as an anticonvulsant, analgesic, sedative, anti-asthma, anti-immune drug since ancient times. The aim of this review is to provide an overview of the abundant efforts of scientists in developing analytical techniques and performing pharmacokinetic studies of G. elata and its constituents, including sample pretreatment methods, analytical techniques, absorption, distribution, metabolism, excretion (ADME) and influence factors to its pharmacokinetics. Based on the reported pharmacokinetic property data of G. elata and its constituents, it is hoped that more studies will focus on the development of rapid and sensitive analytical techniques, discovering new therapeutic uses and understanding the specific in vivo mechanisms of action of G. elata and its constituents from the pharmacokinetic viewpoint in the near future. The present review discusses analytical techniques and pharmacokinetics of G. elata and its constituents reported from 1985 onwards. Full article

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Open AccessArticle

Dereplication-Guided Isolation of New Phenylpropanoid-Substituted Diglycosides from Cistanche salsa and Their Inhibitory Activity on NO Production in Macrophage

by Jongmin Ahn¹, Hee-Sung Chae², Young-Won Chin² and Jinwoong Kim^1,*

¹ College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 08826, Korea

² College of Pharmacy and Integrated Research Institute for Drug Development, Dongguk University-Seoul, Gyeonggi-do 10326, Korea

Molecules 2017, 22(7), 1138; https://doi.org/10.3390/molecules22071138 - 8 Jul 2017

Cited by 7 | Viewed by 4048

Abstract

Dereplication allows for a rapid identification of known and unknown compounds in plant extracts. In this study, we performed liquid chromatography-mass spectroscopy (LC-MS)- based dereplication using data from ESI⁺ QTOF-MS for the analysis of phenylpropanoid-substituted diglycosides, the major active constituents of Cistanche [...] Read more.

Dereplication allows for a rapid identification of known and unknown compounds in plant extracts. In this study, we performed liquid chromatography-mass spectroscopy (LC-MS)- based dereplication using data from ESI⁺ QTOF-MS for the analysis of phenylpropanoid-substituted diglycosides, the major active constituents of Cistanche salsa (C. A. Mey.) Beck. Using TOF-MS alone, the substructures of these compounds could be unambiguously confirmed based on the characteristic fragmentation patterns of various product ions. HPLC-MS based profiling of C. salsa also allowed for the detection of new phenylpropanoid-substituted diglycosides from this plant. Of them, five new phenylpropanoid-substituted diglycosides, named cistansalsides A–E (5, 6, 12, 17 and 18), were isolated. Their structures were elucidated through spectroscopic methods including NMR and MS analysis. All the isolates were tested for their inhibitory activity against NO production in RAW 264.7 cells stimulated by LPS. Of the tested compounds, compounds 5, 11, 13 and 18 showed moderate inhibitory activity on inducible NO synthase. Compounds 11, 13 and 18 also inhibited the phosphorylation of NF-κB in macrophages. None of the compounds displayed significant cytotoxicity. Full article

(This article belongs to the Section Natural Products Chemistry)

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Open AccessArticle

Antifungal and Ichthyotoxic Sesquiterpenoids from Santalum album Heartwood

by Tae Hoon Kim^1,2, Tsutomu Hatano², Keinosuke Okamoto², Takashi Yoshida², Hiroshi Kanzaki³, Michiko Arita⁴ and Hideyuki Ito^2,4,*

¹ Department of Food Science and Biotechnology, Daegu University, Gyeongsan 38453, Korea

² Faculty of Pharmaceutical Sciences, Okayama University, Tsushima, Okayama 700-8530, Japan

³ Faculty of Agriculture, Okayama University, Tsushima, Okayama 700-8530, Japan

⁴ Faculty of Health and Welfare Science, Okayama Prefectural University, Soja, Okayama 719-1197, Japan

Molecules 2017, 22(7), 1139; https://doi.org/10.3390/molecules22071139 - 8 Jul 2017

Cited by 19 | Viewed by 6316

Abstract

In our continuing study on a survey of biologically active natural products from heartwood of Santalum album (Southwest Indian origin), we newly found potent fish toxic activity of an n-hexane soluble extract upon primary screening using killifish (medaka) and characterized α-santalol and [...] Read more.

In our continuing study on a survey of biologically active natural products from heartwood of Santalum album (Southwest Indian origin), we newly found potent fish toxic activity of an n-hexane soluble extract upon primary screening using killifish (medaka) and characterized α-santalol and β-santalol as the active components. The toxicity (median tolerance limit (TLm) after 24 h at 1.9 ppm) of α-santalol was comparable with that of a positive control, inulavosin (TLm after 24 h at 1.3 ppm). These fish toxic compounds including inulavosin were also found to show a significant antifungal effect against a dermatophytic fungus, Trichophyton rubrum. Based on a similarity of the morphological change of the immobilized Trichophyton hyphae in scanning electron micrographs between treatments with α-santalol and griseofulvin (used as the positive control), inhibitory effect of α-santalol on mitosis (the antifungal mechanism proposed for griseofulvin) was assessed using sea urchin embryos. As a result, α-santalol was revealed to be a potent antimitotic agent induced by interference with microtubule assembly. These data suggested that α-santalol or sandalwood oil would be promising to further practically investigate as therapeutic agent for cancers as well as fungal skin infections. Full article

(This article belongs to the Special Issue Diversity of Terpenoids)

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Open AccessArticle

Phenolics from Mikania micrantha and Their Antioxidant Activity

by Li-Mei Dong^1,†, Xu-Chao Jia^2,†, Qing-Wen Luo³, Qiang Zhang³, Bi Luo³, Wen-Bin Liu³, Xu Zhang¹, Qiao-Lin Xu^4,* and Jian-Wen Tan^1,3,*

¹ State Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources/Guangdong Key Laboratory for Innovative Development and Utilization of Forest Plant Germplasm, College of Forestry and Landscape Architecture, South China Agricultural University, Guangzhou 510642, China

² Key Laboratory of Functional Foods, Ministry of Agriculture/Guangdong Key Laboratory of Agricultural Products Processing/Sericultural & Agri-food Research Institute, Guangdong Academy of Agricultural Sciences, Guangzhou 510610, China

³ Guangdong Provincial Key Laboratory of Applied Botany, South China Botanical Garden, Chinese Academy of Sciences, Guangzhou 510650, China

⁴ Guangdong Provincial Key Laboratory of Bio-control for the Forest Disease and Pest, Guangdong Academy of Forestry, Guangzhou 510520, China

^† These authors contributed equally to this work.

Molecules 2017, 22(7), 1140; https://doi.org/10.3390/molecules22071140 - 8 Jul 2017

Cited by 29 | Viewed by 6180

Abstract

A phytochemical study on the aerial parts of Mikania micrantha led to the isolation of two new phenolic compounds, benzyl 5-O-β-d-glucopyranosyl-2,5-dihydroxybenzoate (1) and (7S,8R)-threo-dihydroxydehydrodiconiferyl alcohol 9-acetate (2), together with [...] Read more.

A phytochemical study on the aerial parts of Mikania micrantha led to the isolation of two new phenolic compounds, benzyl 5-O-β-d-glucopyranosyl-2,5-dihydroxybenzoate (1) and (7S,8R)-threo-dihydroxydehydrodiconiferyl alcohol 9-acetate (2), together with twelve known compounds, benzyl 2-O-β-d-glucopyranosyl-2,6-dihydroxybenzoate (3), 4-allyl-2,6-dimethoxyphenol glucoside (4), (+)-isolariciresinol (5), icariol A₂ (6), 9,10-dihydroxythymol (7), 8,9,10-trihydroxythymol (8), caffeic acid (9), p-coumaric acid (10), ethyl protocatechuate (11), procatechuic aldehyde (12), 4-hydroxybenzoic acid (13), and hydroquinone (14). Their structures were elucidated on the basis of extensive spectroscopic analysis. Except 8 and 9, all the other compounds were isolated from this plant species for the first time. The antioxidant activity of those isolated compounds were evaluated using three different assays. Compounds 1, 2, 3, 9, 10, 13, and 14 demonstrated significant 2,2′-azinobis-(3-ethylbenzthiazoline-6-sulphonic acid) (ABTS) free radical cation scavenging activity ranging from SC₅₀ 0.31 to 4.86 µM, which were more potent than l-ascorbic acid (SC₅₀ = 10.48 µM). Compounds 5, 9, 11, and 12 exhibited more potent 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity (SC₅₀ = 16.24–21.67 µM) than l-ascorbic acid (39.48 µM). Moreover, the ferric reducing antioxidant power (FRAP) of compounds 2, 5, 9, and 11 were discovered to be also comparable to or even more potent than l-ascorbic acid. Full article

(This article belongs to the Section Natural Products Chemistry)

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Open AccessFeature PaperArticle

Metal-Mediated Addition of N-Nucleophiles to Isocyanides: Mechanistic Aspects

by Maxim L. Kuznetsov^1,2,*

and Vadim Yu. Kukushkin²

¹ Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, Lisbon 1049-001, Portugal

² International Group on Organometallic Chemistry, Institute of Chemistry, Saint Petersburg State University, Universitetskaya Nab., 7/9, Saint Petersburg 199034, Russia

Molecules 2017, 22(7), 1141; https://doi.org/10.3390/molecules22071141 - 8 Jul 2017

Cited by 7 | Viewed by 4777

Abstract

Despite the long history of the investigation of nucleophilic addition to metal-bound isocyanides, some important aspects of the reaction mechanism remain unclear even for the simplest systems. In this work, the addition of the sp³-N, sp²-N, and mixed sp [...] Read more.

Despite the long history of the investigation of nucleophilic addition to metal-bound isocyanides, some important aspects of the reaction mechanism remain unclear even for the simplest systems. In this work, the addition of the sp³-N, sp²-N, and mixed sp²/sp³-N nucleophiles (i.e., HNMe₂, HN=CPh₂, and H₂N–N=CPh₂, respectively) to isocyanides C≡NR coordinated to the platinum(II) centers in the complexes cis-[Pt(C≡NCy)(2-pyz)(dppe)]⁺ (2-pyz = 2-pyrazyl, dmpe = Me₂PCH₂CH₂PMe₂) and cis-[PtCl₂(C≡NXyl)(C≡NMe)] was studied in detail by theoretical (DFT) methods. The mechanism of these reactions is stepwise associative rather than concerted and it includes the addition of a nucleophile to the isocyanide C atom, deprotonation of the nucleophilic moiety in the resulting intermediate, and protonation of the isocyanide N atom to give the final product. The calculated activation energy (ΔG^≠) of all reactions is in the range of 19.8–22.4 kcal/mol. Full article

(This article belongs to the Section Computational and Theoretical Chemistry)

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Open AccessArticle

Synthesis and Study of Fe-Doped Bi₂S₃ Semimagnetic Nanocrystals Embedded in a Glass Matrix

by Ricardo S. Silva^1,*, Hanna D. Mikhail², Eder V. Guimarães¹, Elis R. Gonçalves¹

, Nilo F. Cano³ and Noelio O. Dantas⁴

¹ Departamento de Física, Instituto de Ciências Exatas, Naturais e Educação (ICENE), Universidade Federal do Triângulo Mineiro, Uberaba 38025–180, Minas Gerais, Brazil

² Departamento de Engenharia Mecânica, Instituto de Ciências Tecnológicas e Exatas (ICTE), Universidade Federal do Triângulo Mineiro, Uberaba 38064–200, Minas Gerais, Brazil

³ Instituto do Mar, Universidade Federal de São Paulo, Santos 11070–100, São Paulo, Brazil

⁴ Laboratório de Novos Materiais Isolantes e Semicondutores (LNMIS), Instituto de Física, Universidade Federal de Uberlândia, Uberlândia 38400–902, Minas Gerais, Brazil

Molecules 2017, 22(7), 1142; https://doi.org/10.3390/molecules22071142 - 11 Jul 2017

Cited by 26 | Viewed by 6885

Abstract

Iron-doped bismuth sulphide (Bi_2−xFe_xS₃) nanocrystals have been successfully synthesized in a glass matrix using the fusion method. Transmission electron microscopy images and energy dispersive spectroscopy data clearly show that nanocrystals are formed with an average diameter [...] Read more.

Iron-doped bismuth sulphide (Bi_2−xFe_xS₃) nanocrystals have been successfully synthesized in a glass matrix using the fusion method. Transmission electron microscopy images and energy dispersive spectroscopy data clearly show that nanocrystals are formed with an average diameter of 7–9 nm, depending on the thermic treatment time, and contain Fe in their chemical composition. Magnetic force microscopy measurements show magnetic phase contrast patterns, providing further evidence of Fe incorporation in the nanocrystal structure. The electron paramagnetic resonance spectra displayed Fe³⁺ typical characteristics, with spin of 5/2 in the 3d⁵ electronic state, thereby confirming the expected trivalent state of Fe ions in the Bi₂S₃ host structure. Results from the spin polarized density functional theory simulations, for the bulk Fe-doped Bi₂S₃ counterpart, corroborate the experimental fact that the volume of the unit cell decreases with Fe substitutionally doping at Bi1 and Bi2 sites. The Bader charge analysis indicated a pseudo valency charge of 1.322|e| on Fe_Bi₁ and 1.306|e| on Fe_Bi₂ ions, and a spin contribution for the magnetic moment of 5.0 µ_B per unit cell containing one Fe atom. Electronic band structures showed that the (indirect) band gap changes from 1.17 eV for Bi₂S₃ bulk to 0.71 eV (0.74 eV) for Bi₂S₃:Fe_Bi1 (Bi₂S₃:Fe_Bi2). These results are compatible with the 3d⁵ high-spin state of Fe³⁺, and are in agreement with the experimental results, within the density functional theory accuracy. Full article

(This article belongs to the Special Issue Nanocrystals: Synthesis, Characterization and Applications)

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Open AccessReview

Review of Ligand Specificity Factors for CYP1A Subfamily Enzymes from Molecular Modeling Studies Reported to-Date

by Jayalakshmi Sridhar, Navneet Goyal

, Jiawang Liu

and Maryam Foroozesh^*

Department of Chemistry, Xavier University of Louisiana, 1 Drexel Dr., New Orleans, LA 70125, USA

Molecules 2017, 22(7), 1143; https://doi.org/10.3390/molecules22071143 - 8 Jul 2017

Cited by 42 | Viewed by 8663

Abstract

The cytochrome P450 (CYP) family 1A enzymes, CYP1A1 and CYP1A2, are two of the most important enzymes implicated in the metabolism of endogenous and exogenous compounds through oxidation. These enzymes are also known to metabolize environmental procarcinogens into carcinogenic species, leading to the [...] Read more.

The cytochrome P450 (CYP) family 1A enzymes, CYP1A1 and CYP1A2, are two of the most important enzymes implicated in the metabolism of endogenous and exogenous compounds through oxidation. These enzymes are also known to metabolize environmental procarcinogens into carcinogenic species, leading to the advent of several types of cancer. The development of selective inhibitors for these P450 enzymes, mitigating procarcinogenic oxidative effects, has been the focus of many studies in recent years. CYP1A1 is mainly found in extrahepatic tissues while CYP1A2 is the major CYP enzyme in human liver. Many molecules have been found to be metabolized by both of these enzymes, with varying rates and/or positions of oxidation. A complete understanding of the factors that govern the specificity and potency for the two CYP 1A enzymes is critical to the development of effective inhibitors. Computational molecular modeling tools have been used by several research groups to decipher the specificity and potency factors of the CYP1A1 and CYP1A2 substrates. In this review, we perform a thorough analysis of the computational studies that are ligand-based and protein-ligand complex-based to catalog the various factors that govern the specificity/potency toward these two enzymes. Full article

(This article belongs to the Special Issue Special Issue in Honor of Professor Nikolaus (Klaus) Fischer on the Occasion of His 80th Birthday)

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Open AccessArticle

Peptide Nucleic Acids as miRNA Target Protectors for the Treatment of Cystic Fibrosis

by Federica Zarrilli^1,2

, Felice Amato^2,3

, Carmine Marco Morgillo⁴, Brunella Pinto⁴

, Giuliano Santarpia⁴, Nicola Borbone⁴, Stefano D’Errico⁴

, Bruno Catalanotti⁴

, Gennaro Piccialli⁴

, Giuseppe Castaldo^2,3 and Giorgia Oliviero^3,*

¹ Department of Biosciences and Territory, University of Molise, 86170 Isernia, Italy

² CEINGE–Advanced Biotechnologies Scarl, 80131 Napoli, Italy

³ Department of Molecular Medicine and Medical Biotechnologies, University of Naples Federico II, 80131 Napoli, Italy

⁴ Department of Pharmacy, University of Naples Federico II, 80131 Napoli, Italy

Molecules 2017, 22(7), 1144; https://doi.org/10.3390/molecules22071144 - 8 Jul 2017

Cited by 31 | Viewed by 6207

Abstract

Cystic Fibrosis (CF) is one of the most common life shortening conditions in Caucasians. CF is caused by mutations in the CF Transmembrane Conductance Regulator (CFTR) gene which result in reduced or altered CFTR functionality. Several microRNAs (miRNAs) downregulate the expression of CFTR, [...] Read more.

Cystic Fibrosis (CF) is one of the most common life shortening conditions in Caucasians. CF is caused by mutations in the CF Transmembrane Conductance Regulator (CFTR) gene which result in reduced or altered CFTR functionality. Several microRNAs (miRNAs) downregulate the expression of CFTR, thus causing or exacerbating the symptoms of CF. In this context, the design of anti-miRNA agents represents a valid functional tool, but its translation to the clinic might lead to unpredictable side effects because of the interference with the expression of other genes regulated by the same miRNAs. Herein, for the first time, is proposed the use of peptide nucleic acids (PNAs) to protect specific sequences in the 3’UTR (untranslated region) of the CFTR messenger RNA (mRNA) by action of miRNAs. Two PNAs (7 and 13 bases long) carrying the tetrapeptide Gly-SerP-SerP-Gly at their C-end, fully complementary to the 3’UTR sequence recognized by miR-509-3p, have been synthesized and the structural features of target PNA/RNA heteroduplexes have been investigated by spectroscopic and molecular dynamics studies. The co-transfection of the pLuc-CFTR-3´UTR vector with different combinations of PNAs, miR-509-3p, and controls in A549 cells demonstrated the ability of the longer PNA to rescue the luciferase activity by up to 70% of the control, thus supporting the use of suitable PNAs to counteract the reduction in the CFTR expression. Full article

(This article belongs to the Special Issue Molecular Properties and the Applications of Peptide Nucleic Acids)

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Open AccessFeature PaperArticle

Therapeutic Delivery of Butyrylcholinesterase by Brain-Wide Viral Gene Transfer to Mice

by Yang Gao, Liyi Geng, Vicky Ping Chen

and Stephen Brimijoin^*

Department of Molecular Pharmacology and Experimental Therapeutics, Kogod Center on Aging, Mayo Clinic, Rochester, MN 55905, USA

Molecules 2017, 22(7), 1145; https://doi.org/10.3390/molecules22071145 - 8 Jul 2017

Cited by 10 | Viewed by 4389

Abstract

Recent research shows that butyrylcholinesterase (BChE) is not simply a liver enzyme that detoxifies bioactive esters in food and medications. In fact, in pursuing other goals, we recently found that it has an equally important role in regulating the peptide hormone ghrelin and [...] Read more.

Recent research shows that butyrylcholinesterase (BChE) is not simply a liver enzyme that detoxifies bioactive esters in food and medications. In fact, in pursuing other goals, we recently found that it has an equally important role in regulating the peptide hormone ghrelin and its impact on hunger, obesity, and emotions. Here, we present and examine means of manipulating brain BChE levels by viral gene transfer, either regionally or globally, to modulate ghrelin signaling for long-term therapeutic purposes and to set the stage for exploring the neurophysiological impact of such an intervention. Full article

(This article belongs to the Special Issue The Cholinesterases—Structure, Mechanism, Function and Drug Design: The 25th Anniversary of the Solution of the Crystal Structure of Acetylcholinesterase by Joel L. Sussman and Israel Silman)

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Open AccessArticle

Combining NMR Spectroscopy and Chemometrics to Monitor Structural Features of Crude Hep-arin

by Lucio Mauri¹, Maria Marinozzi¹, Giulia Mazzini¹, Richard E. Kolinski², Michael Karfunkle²

, David A. Keire²

and Marco Guerrini^1,*

¹ Institute for Chemical and Biochemical Research G. Ronzoni, via G. Colombo 81, 20133 Milan, Italy

² Division of Pharmaceutical Analysis, Office of Testing and Research, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, 645 S. Newstead Ave., St. Louis, MO 63110, USA

Molecules 2017, 22(7), 1146; https://doi.org/10.3390/molecules22071146 - 8 Jul 2017

Cited by 23 | Viewed by 8117

Abstract

Because of the complexity and global nature of the heparin supply chain, the control of heparin quality during manufacturing steps is essential to ensure the safety of the final active pharmaceutical ingredient (API). For this reason, there is a need to develop consistent [...] Read more.

Because of the complexity and global nature of the heparin supply chain, the control of heparin quality during manufacturing steps is essential to ensure the safety of the final active pharmaceutical ingredient (API). For this reason, there is a need to develop consistent analytical methods able to assess the quality of heparin early in production (i.e., as the crude heparin before it is purified to API under cGMP conditions). Although a number of analytical techniques have been applied to characterize heparin APIs, few of them have been applied for crude heparin structure and composition analyses. Here, to address this issue, NMR spectroscopy and chemometrics were applied to characterize 88 crude heparin samples. The samples were also analyzed by strong anion exchange HPLC (SAX-HPLC) as an orthogonal check of the purity levels of the crudes analyzed by NMR. The HPLC data showed that the chemometric analysis of the NMR data differentiated the samples based on their purity. These orthogonal approaches differentiated samples according their glycosaminoglycan (GAG) composition and their mono and disaccharide composition and structure for each GAG family (e.g., heparin/heparan, dermatan sulfate, and chondroitin sulfate A). Moreover, quantitative HSQC and multivariate analysis (PCA) were used to distinguish between crude heparin of different animal and tissue sources. Full article

(This article belongs to the Special Issue Looking Forward to the Future of Heparin: New Sources, Developments and Applications)

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Open AccessFeature PaperArticle

Synthesis and Structure of the Inclusion Complex {NdQ[5]K@Q[10](H₂O)₄}·4NO₃·20H₂O

by Li Xia Chen¹, Jing Lan Kan², Hang Cong¹, Timothy J. Prior³

, Zhu Tao¹, Xin Xiao^1,* and Carl Redshaw^3,*

¹ Key Laboratory of Macrocyclic and Supramolecular Chemistry of Guizhou Province, Guizhou University, Guiyang 550025, China

² College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong Normal University, Jinan 250014, China

³ Department of Chemistry, School of Mathematics and Physical Sciences, University of Hull, Hull HU6 7RX, UK

Molecules 2017, 22(7), 1147; https://doi.org/10.3390/molecules22071147 - 9 Jul 2017

Cited by 9 | Viewed by 5244

Abstract

Heating a mixture of Nd(NO₃)₃·6H₂O, KCl, Q[10] and Q[5] in HCl for 10 min affords the inclusion complex {NdQ[5]K@Q[10](H₂O)₄}·4NO₃·20H₂O. The structure of the inclusion complex has been investigated by single crystal X-ray diffraction and by X-ray Photoelectron spectroscopy (XPS). Full article

(This article belongs to the Special Issue Calixarenes, Pillararenes, and Cucurbiturils)

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Open AccessReview

β-Ocimene, a Key Floral and Foliar Volatile Involved in Multiple Interactions between Plants and Other Organisms

by Gerard Farré-Armengol^1,2,3,*

, Iolanda Filella^1,2, Joan Llusià^1,2 and Josep Peñuelas^1,2

¹ CSIC, Global Ecology Unit CREAF-CSIC-UAB, Bellaterra, 08193 Barcelona, Catalonia, Spain

² CREAF, Cerdanyola del Vallès, 08193 Barcelona, Catalonia, Spain

³ Department of Ecology and Evolution, University of Salzburg, Hellbrunnerstraße 34, 5020 Salzburg, Austria

Molecules 2017, 22(7), 1148; https://doi.org/10.3390/molecules22071148 - 13 Jul 2017

Cited by 123 | Viewed by 14801

Abstract

β-Ocimene is a very common plant volatile released in important amounts from the leaves and flowers of many plant species. This acyclic monoterpene can play several biological functions in plants, by potentially affecting floral visitors and also by mediating defensive responses to herbivory. [...] Read more.

β-Ocimene is a very common plant volatile released in important amounts from the leaves and flowers of many plant species. This acyclic monoterpene can play several biological functions in plants, by potentially affecting floral visitors and also by mediating defensive responses to herbivory. The ubiquity and high relative abundance of β-ocimene in the floral scents of species from most plant families and from different pollination syndromes (ranging from generalism to specialism) strongly suggest that this terpenoid may play an important role in the attraction of pollinators to flowers. We compiled abundant evidence from published studies that supports β-ocimene as a generalist attractant of a wide spectrum of pollinators. We found no studies testing behavioural responses of pollinators to β-ocimene, that could directly demonstrate or deny the function of β-ocimene in pollinator attraction; but several case studies support that the emissions of β-ocimene in flowers of different species follow marked temporal and spatial patterns of emission, which are typical from floral volatile organic compound (VOC) emissions that are involved in pollinator attraction. Furthermore, important β-ocimene emissions are induced from vegetative plant tissues after herbivory in many species, which have relevant functions in the establishment of tritrophic interactions. We thus conclude that β-ocimene is a key plant volatile with multiple relevant functions in plants, depending on the organ and the time of emission. Experimental behavioural studies on pure β-ocimene conducted with pollinating insects will be necessary to prove the assumptions made here. Full article

(This article belongs to the Collection Recent Advances in Flavors and Fragrances)

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Open AccessReview

Crystallization of Covalent Organic Frameworks for Gas Storage Applications

by Lijuan Zhu

and Yue-Biao Zhang^*

School of Physical Science and Technology, ShanghaiTech University, Shanghai 201210, China

Molecules 2017, 22(7), 1149; https://doi.org/10.3390/molecules22071149 - 10 Jul 2017

Cited by 135 | Viewed by 21933

Abstract

Covalent organic frameworks (COFs) have emerged as a new class of crystalline porous materials prepared by integrating organic molecular building blocks into predetermined network structures entirely through strong covalent bonds. The consequently encountered “crystallization problem” has been conquered by dynamic covalent chemistry in [...] Read more.

Covalent organic frameworks (COFs) have emerged as a new class of crystalline porous materials prepared by integrating organic molecular building blocks into predetermined network structures entirely through strong covalent bonds. The consequently encountered “crystallization problem” has been conquered by dynamic covalent chemistry in syntheses and reticular chemistry in materials design. In this contribution, we have reviewed the progress in the crystallization of COF materials and their hydrogen, methane and carbon dioxide gas storage properties for clean energy applications. Full article

(This article belongs to the Special Issue Covalent Organic Frameworks and Related Porous Organic Materials)

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Open AccessArticle

Design, Synthesis, and Biological Activity of New Triazole and Nitro-Triazole Derivatives as Antifungal Agents

by Hossein Sadeghpour¹, Soghra Khabnadideh¹, Kamiar Zomorodian², Keyvan Pakshir², Khadijeh Hoseinpour¹, Nabiollah Javid¹, Ehsan Faghih-Mirzaei³ and Zahra Rezaei^1,*

¹ Department of Medicinal Chemistry, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz 7146864685, Iran

² Department of Medical Mycology and Parasitology, School of Medicine, Shiraz University of Medical Sciences, Shiraz 7134845794, Iran

³ Department of Medicinal Chemistry, School of Pharmacy, Kerman University of Medical Sciences, Kerman 7616911319, Iran

Molecules 2017, 22(7), 1150; https://doi.org/10.3390/molecules22071150 - 10 Jul 2017

Cited by 39 | Viewed by 7343

Abstract

In this study two series of fluconazole derivatives bearing nitrotriazole (series A) or piperazine ethanol (series B) side chain were designed and synthesized and then docked in the active site of lanosterol 14α-demethylase enzyme (1EA1) using the Autodock 4.2 program (The scripps research [...] Read more.

In this study two series of fluconazole derivatives bearing nitrotriazole (series A) or piperazine ethanol (series B) side chain were designed and synthesized and then docked in the active site of lanosterol 14α-demethylase enzyme (1EA1) using the Autodock 4.2 program (The scripps research institute, La Jolla, CA, USA). The structures of synthesized compound were confirmed by various methods including elemental and spectral (NMR, CHN, and Mass) analyses. Then antifungal activities of the synthesized compound were tested against several natural and clinical strains of fungi using a broth microdilution assay against several standard and clinical fungi. Nitrotriazole derivatives showed excellent and desirable antifungal activity against most of the tested fungi. Among the synthesized compounds, 5a–d and 5g, possessing nitrotriazole moiety, showed maximum antifungal activity, in particular against several fluconazole-resistant fungi. Full article

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Open AccessArticle

Engineering of a Potent Recombinant Lectin-Toxin Fusion Protein to Eliminate Human Pluripotent Stem Cells

by Hiroaki Tateno^*, Fumi Minoshima and Sayoko Saito

Biotechnology Research Institute for Drug Discovery (BRD), National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba Central 2, 1-1-1 Umezono, Tsukuba, Ibaraki 305-8568, Japan

Molecules 2017, 22(7), 1151; https://doi.org/10.3390/molecules22071151 - 10 Jul 2017

Cited by 17 | Viewed by 4867

Abstract

The use of human pluripotent stem cells (hPSCs) such as human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs) in regenerative medicine is hindered by their tumorigenic potential. Previously, we developed a recombinant lectin-toxin fusion protein of the hPSC-specific lectin [...] Read more.

The use of human pluripotent stem cells (hPSCs) such as human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs) in regenerative medicine is hindered by their tumorigenic potential. Previously, we developed a recombinant lectin-toxin fusion protein of the hPSC-specific lectin rBC2LCN, which has a 23 kDa catalytic domain (domain III) of Pseudomonas aeruginosa exotoxin A (rBC2LCN-PE23). This fusion protein could selectively eliminate hPSCs following its addition to the cell culture medium. Here we conjugated rBC2LCN lectin with a 38 kDa domain of exotoxin A containing domains Ib and II in addition to domain III (PE38). The developed rBC2LCN-PE38 fusion protein could eliminate 50% of 201B7 hPSCs at a concentration of 0.003 μg/mL (24 h incubation), representing an approximately 556-fold higher activity than rBC2LCN-PE23. Little or no effect on human fibroblasts, human mesenchymal stem cells, and hiPSC-derived hepatocytes was observed at concentrations lower than 1 μg/mL. Finally, we demonstrate that rBC2LCN-PE38 selectively eliminates hiPSCs from a mixed culture of hiPSCs and hiPSC-derived hepatocytes. Since rBC2LCN-PE38 can be prepared from soluble fractions of E. coli culture at a yield of 9 mg/L, rBC2LCN-PE38 represents a practical reagent to remove human pluripotent stem cells residing in cultured cells destined for transplantation. Full article

(This article belongs to the Special Issue Protein-Carbohydrate Interactions)

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Open AccessArticle

The Evaluation of the Reactivating and Neuroprotective Efficacy of Two Newly Prepared Bispyridinium Oximes (K305, K307) in Tabun-Poisoned Rats—A Comparison with Trimedoxime and the Oxime K203

by Jiri Kassa^1,*, Jan Misik¹, Jana Hatlapatkova¹, Jana Zdarova Karasova¹, Vendula Sepsova¹, Filip Caisberger^1,2 and Jaroslav Pejchal¹

¹ Department of Toxicology and Military Pharmacy, Faculty of Military Health Sciences, University of Defense, Trebesska 1575, 500 01 Hradec Kralove, Czech Republic

² Clinic of Neurology, Faculty Hospital Hradec Kralove, Sokolovska 581, 500 01 Hradec Kralove, Czech Republic

Molecules 2017, 22(7), 1152; https://doi.org/10.3390/molecules22071152 - 11 Jul 2017

Cited by 8 | Viewed by 3458

Abstract

The ability of two newly developed oximes (K305, K307) to protect tabun-poisoned rats from tabun-induced inhibition of brain acetylcholinesterase, acute neurotoxic signs and symptoms and brain damage was compared with that of the oxime K203 and trimedoxime. The reactivating and neuroprotective effects of [...] Read more.

The ability of two newly developed oximes (K305, K307) to protect tabun-poisoned rats from tabun-induced inhibition of brain acetylcholinesterase, acute neurotoxic signs and symptoms and brain damage was compared with that of the oxime K203 and trimedoxime. The reactivating and neuroprotective effects of the oximes studied combined with atropine on rats poisoned with tabun at a sublethal dose were evaluated. The reactivating efficacy of a newly developed oxime K305 is lower compared to the reactivating efficacy of the oxime K203 and trimedoxime while the ability of the oxime K307 to reactivate tabun-inhibited acetylcholinesterase (AChE) in the brain roughly corresponds to the reactivating efficacy of the oxime K203 and it is slightly lower compared to trimedoxime. In addition, only one newly developed oxime (K307) combined with atropine was able to markedly decrease tabun-induced neurotoxicity although it did not eliminate all tabun-induced acute neurotoxic signs and symptoms. These results correspond to the histopathological evaluation of tabun-induced brain damage. Therefore, the newly developed oximes are not suitable for the replacement of commonly used oximes (especially trimedoxime) in the treatment of acute tabun poisonings. Full article

(This article belongs to the Special Issue The Cholinesterases—Structure, Mechanism, Function and Drug Design: The 25th Anniversary of the Solution of the Crystal Structure of Acetylcholinesterase by Joel L. Sussman and Israel Silman)

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Open AccessArticle

Warfarin and Flavonoids Do Not Share the Same Binding Region in Binding to the IIA Subdomain of Human Serum Albumin

by Hrvoje Rimac¹, Claire Dufour²

, Željko Debeljak^3,4, Branka Zorc¹ and Mirza Bojić^1,*

¹ Department of Medicinal Chemistry, University of Zagreb, Faculty of Pharmacy and Biochemistry, Ante Kovačića 1, 10000 Zagreb, Croatia

² UMR408 SQPOV, Safety and Quality of Plant Products, INRA, Avignon University, 228 Route de l’Aérodrome, 84000 Avignon, France

³ Institute of Clinical Laboratory Diagnostics, Osijek University Hospital Center, Josipa Huttlera 4, 31000 Osijek, Croatia

⁴ Department of Pharmacology, School of Medicine, University of Osijek, Cara Hadrijana 10/E, 31000 Osijek, Croatia

Molecules 2017, 22(7), 1153; https://doi.org/10.3390/molecules22071153 - 11 Jul 2017

Cited by 37 | Viewed by 6987

Abstract

Human serum albumin (HSA) binds a variety of xenobiotics, including flavonoids and warfarin. The binding of another ligand to the IIA binding site on HSA can cause warfarin displacement and potentially the elevation of its free concentration in blood. Studies dealing with flavonoid-induced [...] Read more.

Human serum albumin (HSA) binds a variety of xenobiotics, including flavonoids and warfarin. The binding of another ligand to the IIA binding site on HSA can cause warfarin displacement and potentially the elevation of its free concentration in blood. Studies dealing with flavonoid-induced warfarin displacement from HSA provided controversial results: estimated risk of displacement ranged from none to serious. To resolve these controversies, in vitro study of simultaneous binding of warfarin and eight different flavonoid aglycons and glycosides to HSA was carried out by fluorescence spectroscopy as well as molecular docking. Results show that warfarin and flavonoids do not share the same binding region in binding to HSA. Interactions were only observed at high warfarin concentrations not attainable under recommended dosing regimes. Docking experiments show that flavonoid aglycons and glycosides do not bind at warfarin high affinity sites, but rather to different regions within the IIA HSA subdomain. Thus, the risk of clinically significant warfarin–flavonoid interaction in binding to HSA should be regarded as negligible. Full article

(This article belongs to the Section Natural Products Chemistry)

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Open AccessArticle

Synthesis and Evaluation of New Quinoxaline Derivatives of Dehydroabietic Acid as Potential Antitumor Agents

by Wen Gu^1,*, Shuang Wang^1,†, Xiaoyan Jin^1,†, Yaliang Zhang², Dawei Hua¹, Tingting Miao¹, Xubing Tao¹ and Shifa Wang¹

¹ Jiangsu Key Lab of Biomass-Based Green Fuels and Chemicals, College of Chemical Engineering, Nanjing Forestry University, Nanjing 210037, China

² The State Key Lab of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, China

^† The two authors contributed equally to this work.

Molecules 2017, 22(7), 1154; https://doi.org/10.3390/molecules22071154 - 11 Jul 2017

Cited by 27 | Viewed by 4950

Abstract

A series of new quinoxaline derivatives of dehydroabietic acid (DAA) were designed and synthesized as potential antitumor agents. Their structures were characterized by IR, ¹H-NMR, ¹³C-NMR, and MS spectra and elemental analyses. All the new compounds were screened for their in [...] Read more.

A series of new quinoxaline derivatives of dehydroabietic acid (DAA) were designed and synthesized as potential antitumor agents. Their structures were characterized by IR, ¹H-NMR, ¹³C-NMR, and MS spectra and elemental analyses. All the new compounds were screened for their in vitro antiproliferative activities against three human cancer cell lines (MCF-7, SMMC-7721 and HeLa) and noncancerous human hepatocyte cells (LO2). A cytotoxic assay manifested that compound 4b showed the most potent cytotoxic activity against the three cancer cell lines, with IC₅₀ values of 1.78 ± 0.36, 0.72 ± 0.09 and 1.08 ± 0.12 μM, respectively, and a substantially lower cytotoxicity to LO2 cells (IC₅₀: 11.09 ± 0.57 μM). Moreover, the cell cycle analysis suggested that compound 4b caused cell cycle arrest of SMMC-7721 cells at the G0/G1 phase. In a Hoechst 33258 staining assay, compound 4b caused considerable morphological changes of the nuclei of SMMC-7721 cells, correlated with cell apoptosis. In addition, an Annexin V-FITC/PI dual staining assay confirmed that compound 4b could induce the apoptosis of SMMC-7721 cells in a dose-dependent manner. Full article

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Open AccessArticle

Site-Specific PEGylated Adeno-Associated Viruses with Increased Serum Stability and Reduced Immunogenicity

by Tianzhuo Yao^†, Xueying Zhou^†

, Chuanling Zhang^*, Xiaojuan Yu, Zhenyu Tian, Lihe Zhang and Demin Zhou^*

¹ State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 100191 Beijing, China

^† These authors contributed equally to this work.

Molecules 2017, 22(7), 1155; https://doi.org/10.3390/molecules22071155 - 11 Jul 2017

Cited by 37 | Viewed by 11673

Abstract

Adeno-associated virus (AAV) is one of the most extensively studied and utilized viral vectors in clinical gene transfer research. However, the serum instability and immunogenicity of AAV vectors significantly limit their application. Here, we endeavored to overcome these limitations by developing a straightforward [...] Read more.

Adeno-associated virus (AAV) is one of the most extensively studied and utilized viral vectors in clinical gene transfer research. However, the serum instability and immunogenicity of AAV vectors significantly limit their application. Here, we endeavored to overcome these limitations by developing a straightforward approach for site-specific PEGylation of AAV via genetic code expansion. This technique includes incorporation of the azide moiety into the AAV capsid protein followed by orthogonal and stoichiometric conjugation of a variety of polyethylene glycols (PEGs) through click chemistry. Using this approach, only the chosen site(s) was consistently PEGylated under mild conditions, preventing nonselective conjugation. Upon a series of in vitro examinations, AAVs conjugated with 20-kD PEG at sites Q325+1, S452+1, and R585+1 showed a 1.7- to 2.4-fold stability improvement in pooled human serum and a nearly twofold reduction in antibody recognition. Subsequent animal research on Sprague Dawley rats displayed a promising 20% reduction in antibody inducement and a higher virus titer in the blood. Together, our data demonstrate successful protection of an AAV vector from antibody neutralization and blood clearance, thereby increasing the efficiency of therapeutic gene delivery. Full article

(This article belongs to the Special Issue Nucleic Acid Chemistry and Nucleic Acid Drugs: A Themed Issue in Honor of Professor Lihe Zhang on the Occasion of His 80th Birthday)

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Open AccessArticle

Homogenate-assisted Vacuum-powered Bubble Extraction of Moso Bamboo Flavonoids for On-line Scavenging Free Radical Capacity Analysis

by Yinnan Sun^†, Kui Yang^†, Qin Cao, Jinde Sun, Yu Xia, Yinhang Wang, Wei Li, Chunhui Ma^* and Shouxin Liu^*

¹ College of Material Science and Engineering, Northeast Forestry University, Harbin 150040, China

^† Authors contributed equally to this work.

Molecules 2017, 22(7), 1156; https://doi.org/10.3390/molecules22071156 - 11 Jul 2017

Cited by 17 | Viewed by 4980

Abstract

A homogenate-assisted vacuum-powered bubble extraction (HVBE) method using ethanol was applied for extraction of flavonoids from Phyllostachys pubescens (P. pubescens) leaves. The mechanisms of homogenate-assisted extraction and vacuum-powered bubble generation were discussed in detail. Furthermore, a method for the rapid determination of flavonoids [...] Read more.

A homogenate-assisted vacuum-powered bubble extraction (HVBE) method using ethanol was applied for extraction of flavonoids from Phyllostachys pubescens (P. pubescens) leaves. The mechanisms of homogenate-assisted extraction and vacuum-powered bubble generation were discussed in detail. Furthermore, a method for the rapid determination of flavonoids by HPLC was established. HVBE followed by HPLC was successfully applied for the extraction and quantification of four flavonoids in P. pubescens, including orientin, isoorientin, vitexin, and isovitexin. This method provides a fast and effective means for the preparation and determination of plant active components. Moreover, the on-line antioxidant capacity, including scavenging positive ion and negative ion free radical capacity of different fractions from the bamboo flavonoid extract was evaluated. Results showed that the scavenging DPPH˙ free radical capacity of vitexin and isovitexin was larger than that of isoorientin and orientin. On the contrary, the scavenging ABTS⁺˙free radical capacity of isoorientin and orientin was larger than that of vitexin and isovitexin. Full article

(This article belongs to the Special Issue Green Extraction of Natural Product: Innovative Techniques, Alternative Solvents and Original Procedures)

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Open AccessArticle

2,5-Dihydroxyacetophenone Induces Apoptosis of Multiple Myeloma Cells by Regulating the MAPK Activation Pathway

by Jeong-Hyeon Ko¹, Jae Hwi Lee¹, Sang Hoon Jung²

, Seok-Geun Lee¹, Arunachalam Chinnathambi³, Sulaiman Ali Alharbi³, Woong Mo Yang¹, Jae-Young Um¹, Gautam Sethi^3,4,5,*

and Kwang Seok Ahn^1,*

¹ College of Korean Medicine, Kyung Hee University, 24 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea

² Natural Products Research Institute, Korean Institute of Science and Technology, 679 Saimdang-ro, Gangneung, Gangwon-do 25451, Korea

³ Department of Botany and Microbiology, College of Science, King Saud University, Riyadh 11451, Saudi Arabia

⁴ School of Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University, Perth, WA 6009, Australia

⁵ Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, Singapore

Molecules 2017, 22(7), 1157; https://doi.org/10.3390/molecules22071157 - 11 Jul 2017

Cited by 25 | Viewed by 6100

Abstract

2,5-Dihydroxyacetophenone (DHAP) is an active compound obtained from Radix rehmanniae preparata, which is widely used as a herbal medicine in many Asian countries. DHAP has been found to possess anti-inflammatory, anti-anxiety, and neuroprotective qualities. For the present study, we evaluated the anti-cancer effects [...] Read more.

2,5-Dihydroxyacetophenone (DHAP) is an active compound obtained from Radix rehmanniae preparata, which is widely used as a herbal medicine in many Asian countries. DHAP has been found to possess anti-inflammatory, anti-anxiety, and neuroprotective qualities. For the present study, we evaluated the anti-cancer effects of DHAP on multiple myeloma cells. It was discovered that DHAP downregulated the expression of oncogenic gene products like Bcl-xl, Bcl-2, Mcl-1, Survivin, Cyclin D1, IAP-1, Cyclin E, COX-2, and MMP-9, and upregulated the expression of Bax and p21 proteins, consistent with the induction of G2/M phase cell cycle arrest and apoptosis in U266 cells. DHAP inhibited cell proliferation and induced apoptosis, as characterized by the cleavage of PARP and the activation of caspase-3, caspase-8, and caspase-9. Mitogen-activated protein kinase (MAPK) pathways have been linked to the modulation of the angiogenesis, proliferation, metastasis, and invasion of tumors. We therefore attempted to determine the effect of DHAP on MAPK signaling pathways, and discovered that DHAP treatment induced a sustained activation of JNK, ERK1/2, and p38 MAPKs. DHAP also potentiated the pro-apoptotic and anti-proliferative effects of bortezomib in U266 cells. Our results suggest that DHAP can be an effective therapeutic agent to target multiple myeloma. Full article

(This article belongs to the Collection Bioactive Compounds)

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Open AccessArticle

Comparative Transcriptome Analysis Reveals Adaptive Evolution of Notopterygium incisum and Notopterygium franchetii, Two High-Alpine Herbal Species Endemic to China

by Yun Jia, Mi-Li Liu, Ming Yue, Zhe Zhao, Gui-Fang Zhao and Zhong-Hu Li^*

Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, College of Life Sciences, Northwest University, Xi’an 710069, China

Molecules 2017, 22(7), 1158; https://doi.org/10.3390/molecules22071158 - 11 Jul 2017

Cited by 21 | Viewed by 5878

Abstract

The extreme conditions (e.g., cold, low oxygen, and strong ultraviolet radiation) of the high mountains provide an ideal natural laboratory for studies on speciation and the adaptive evolution of organisms. Up to now, few genome/transcriptome-based studies have been carried out on how plants [...] Read more.

The extreme conditions (e.g., cold, low oxygen, and strong ultraviolet radiation) of the high mountains provide an ideal natural laboratory for studies on speciation and the adaptive evolution of organisms. Up to now, few genome/transcriptome-based studies have been carried out on how plants adapt to conditions at extremely high altitudes. Notopterygium incisum and Notopterygium franchetii (Notopterygium, Apiaceae) are two endangered high-alpine herbal plants endemic to China. To explore the molecular genetic mechanisms of adaptation to high altitudes, we performed high-throughput RNA sequencing (RNA-seq) to characterize the transcriptomes of the two species. In total, more than 130 million sequence reads, 81,446 and 63,153 unigenes with total lengths of 86,924,837 and 62,615,693 bp, were generated for the two herbal species, respectively. OrthoMCL analysis identified 6375 single-copy orthologous genes between N. incisum and N. franchetii. In total, 381 positively-selected candidate genes were identified for both plants by using estimations of the non-synonymous to synonymous substitution rate. At least 18 of these genes potentially participate in RNA splicing, DNA repair, glutathione metabolism and the plant–pathogen interaction pathway, which were further enriched in various functional gene categories possibly responsible for environment adaptation in high mountains. Meanwhile, we detected various transcription factors that regulated the material and energy metabolism in N. incisum and N. franchetii, which probably play vital roles in the tolerance to stress in surroundings. In addition, 60 primer pairs based on orthologous microsatellite-containing sequences between the both Notopterygium species were determined. Finally, 17 polymorphic microsatellite markers (SSR) were successfully characterized for the two endangered species. Based on these candidate orthologous and SSR markers, we detected that the adaptive evolution and species divergence of N. incisum and N. franchetii were significantly associated with the extremely heterogeneous environments and climatic oscillations in high-altitude areas. This work provides important insights into the molecular mechanisms of adaptation to high-altitudes in alpine herbal plants. Full article

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Open AccessArticle

Characterization and Biological Evaluation of Propolis from Poland

by Milena Popova^1,4,*

, Efstathia Giannopoulou²

, Krystyna Skalicka-Woźniak^3,*

, Konstantia Graikou⁴, Jaroslaw Widelski³, Vassya Bankova¹, Haralabos Kalofonos², Gregory Sivolapenko⁵, Katarzyna Gaweł-Bęben⁶

, Beata Antosiewicz⁶ and Ioanna Chinou^4,*

¹ Institute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria

² Clinical Oncology Laboratory, University Hospital of Patras, Patras Medical School, 26504 Rio, Greece

³ Department of Pharmacognosy with Medicinal Plant Unit, Medical University of Lublin, 20093 Lublin, Poland

⁴ Division of Pharmacognosy and Chemistry of Natural Products, Departments of Pharmacy, National and Kapodistrian University of Athens, 15771 Athens, Greece

⁵ Pharmacokinetics Laboratory, Department of Pharmacy, University of Patras, 26504 Rio, Greece

⁶ Department of Cosmetology, University of Information Technology and Management in Rzeszow, 35225 Rzeszów, Poland

Molecules 2017, 22(7), 1159; https://doi.org/10.3390/molecules22071159 - 11 Jul 2017

Cited by 87 | Viewed by 6428

Abstract

In this study, we assessed the therapeutic potential of propolis from Poland and performed chemical analysis by GC–MS, as well as determined its botanical origin. Chemical constituents typical for bud exudates of Populus nigra (section Aigeiros) were determined, however, glycerol esters of [...] Read more.

In this study, we assessed the therapeutic potential of propolis from Poland and performed chemical analysis by GC–MS, as well as determined its botanical origin. Chemical constituents typical for bud exudates of Populus nigra (section Aigeiros) were determined, however, glycerol esters of phenolic acids, as well as unusually high amounts of p-coumaric and ferulic acid and their benzyl esters, were also detected. These constituents are characteristic for buds of Populus tremula (section Leuce). We also evaluated the antiproliferative effect of propolis extracts against nine human cancer cell lines. Additionally, promising antibacterial activity of the dichloromethane extract (Minimal Inhibitory Concentration MIC values of 0.95–1.24 mg/mL), as well as a moderate antifungal activity (MIC values of 1.25–1.40 mg/mL), was noticed. Propolis from Poland appeared as a rich source of antibacterial and antiproliferative compounds and this confirmed that it is a valuable natural product with the potential to improve human health. Full article

(This article belongs to the Section Natural Products Chemistry)

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Open AccessArticle

The Inhibitory Effect of Tartary Buckwheat Extracts on Adipogenesis and Inflammatory Response

by Mak-Soon Lee¹, Yoonjin Shin¹, Sunyoon Jung¹

, Seog-Young Kim¹, Young-Hee Jo², Chong-Tai Kim², Min-Kyu Yun³, Sung-Jin Lee³, Johann Sohn³, Heui-Jong Yu³ and Yangha Kim^1,*

¹ Department of Nutritional Science and Food Management, Ewha Womans University, 52 Ewhayeodae-gil, Seodaemun-gu, Seoul 03760, Korea

² Research Group of Bioprocess Engineering, Korea Food Research Institute, Seongnam, Gyeonggi 13539, Korea

³ R&D Center, SKBioland Co. Ltd., 152, Manhae-ro, Danwon-gu, Ansan-si, Gyeonggi-do 15407, Korea

Molecules 2017, 22(7), 1160; https://doi.org/10.3390/molecules22071160 - 12 Jul 2017

Cited by 31 | Viewed by 5348

Abstract

Tartary buckwheat (Fagopyrum tataricum) has been established globally as a nutritionally important food item, particularly owing to high levels of bioactive compounds such as rutin. This study investigated the effect of tartary buckwheat extracts (TBEs) on adipogenesis and inflammatory response in [...] Read more.

Tartary buckwheat (Fagopyrum tataricum) has been established globally as a nutritionally important food item, particularly owing to high levels of bioactive compounds such as rutin. This study investigated the effect of tartary buckwheat extracts (TBEs) on adipogenesis and inflammatory response in 3T3-L1 cells. TBEs inhibited lipid accumulation, triglyceride content, and glycerol-3-phosphate dehydrogenase (GPDH) activity during adipocyte differentiation of 3T3 L1 cells. The mRNA levels of genes involved in fatty acid synthesis, such as peroxisome proliferator-activated receptor-γ (PPAR-γ), CCAAT/enhancer binding protein-α (CEBP-α), adipocyte protein 2 (aP2), acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), and stearoylcoenzyme A desaturase-1 (SCD-1), were suppressed by TBEs. They also reduced the mRNA levels of inflammatory mediators such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), monocyte chemoattractant protein 1 (MCP-1), and inducible nitric oxide synthase (iNOS). In addition, TBEs were decreased nitric oxide (NO) production. These results suggest that TBEs may inhibit adipogenesis and inflammatory response; therefore, they seem to be beneficial as a food ingredient to prevent obesity-associated inflammation. Full article

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Open AccessArticle

Effect of UV-C Radiation, Ultra-Sonication Electromagnetic Field and Microwaves on Changes in Polyphenolic Compounds in Chokeberry (Aronia melanocarpa)

by Tomasz Cebulak^1,†, Jan Oszmiański^2,†, Ireneusz Kapusta^1,†

and Sabina Lachowicz^2,*,†

¹ Department of Food Technology and Human Nutrition, Faculty of Biology and Agriculture, Rzeszów University, 4 Zelwerowicza Street, 35-601 Rzeszów, Poland

² Department of Fruit, Vegetable and Plant Nutraceutical Technology, Wrocław University of Environmental and Life Science, 37, Chełmońskiego Street, 51-630 Wrocław, Poland

^† These authors contributed equally to this work.

Molecules 2017, 22(7), 1161; https://doi.org/10.3390/molecules22071161 - 12 Jul 2017

Cited by 20 | Viewed by 5284

Abstract

Chokeberry fruits are highly valued for their high content of polyphenolic compounds. The use of such abiotic stress factors as UV-C radiation, an electromagnetic field, microwave radiation, and ultrasound, at different operation times, caused differentiation in the contents of anthocyanins, phenolic acids, flavonols, [...] Read more.

Chokeberry fruits are highly valued for their high content of polyphenolic compounds. The use of such abiotic stress factors as UV-C radiation, an electromagnetic field, microwave radiation, and ultrasound, at different operation times, caused differentiation in the contents of anthocyanins, phenolic acids, flavonols, and flavan-3-ols. Samples were analyzed for contents of polyphenolics with ultra-performance liquid chromatography and photodiode detector-quadrupole/time-of-flight mass spectrometry (UPLC-PDA-MS/MS). The analysis showed that after exposure to abiotic stress factors, the concentration of anthocyanins ranged from 3587 to 6316 mg/100 g dry matter (dm) that constituted, on average, 67.6% of all identified polyphenolic compounds. The second investigated group included phenolic acids with the contents ranging between 1480 and 2444 mg/100 g dm (26.5%); then flavonols within the range of 133 to 243 mg/100 g dm (3.7%), and finally flavan-3-ols fluctuated between 191 and 369 mg/100 g dm (2.2%). The use of abiotic stress factors such as UV-C radiation, microwaves and ultrasound field, in most cases contributed to an increase in the content of the particular polyphenolic compounds in black chokeberry. Under the influence of these factors, increases were observed: in anthocyanin content, of 22%; in phenolic acids, of 20%; in flavonols, of 43%; and in flavan-3-ols, of 30%. Only the use of the electromagnetic field caused a decrease in the content of the examined polyphenolic compounds. Full article

(This article belongs to the Section Natural Products Chemistry)

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Specialized Metabolites of the Lichen Vulpicida pinastri Act as Photoprotective Agents

by Béatrice Legouin^1,*,†, Françoise Lohézic-Le Dévéhat^1,*,†, Solenn Ferron¹, Isabelle Rouaud¹, Pierre Le Pogam^1,2, Laurence Cornevin¹, Michel Bertrand³ and Joël Boustie¹

¹ ISCR-UMR CNRS 6226, Faculté des Sciences Pharmaceutiques et Biologiques, Institut des Sciences Chimiques de Rennes, Université Rennes 1, 2 Av. du Pr. Léon Bernard, 35043 Rennes CEDEX, France

² IETR-UMR CNRS 6164, Institut d’Électronique et de Télécommunications de Rennes, Université Rennes 1, 263 Av. du Général Leclerc, 35042 Rennes CEDEX, France

³ French Lichenological Society, Station D’écologie Forestière, Route de la tour Dénecourt, 77300 Fontainebleau/Avon, France

^† These authors contributed equally to this paper.

Molecules 2017, 22(7), 1162; https://doi.org/10.3390/molecules22071162 - 12 Jul 2017

Cited by 32 | Viewed by 6445

Abstract

The extreme resiliency of lichens to UV radiations makes them an interesting model to find new photoprotective agents acting as UV-blockers and antioxidant. In this research, using a new in vitro method designed to overcome the shortage of material associated to many studies [...] Read more.

The extreme resiliency of lichens to UV radiations makes them an interesting model to find new photoprotective agents acting as UV-blockers and antioxidant. In this research, using a new in vitro method designed to overcome the shortage of material associated to many studies dealing with natural products, we show that the three major compounds isolated from the lichen Vulpicida pinastri, vulpinic acid, pinastric acid and usnic acid, were UV blocker agents. Antioxidant assays evidenced superoxide anion scavenging activity. Combination of the most promising compounds against UVB and UVB radiations, usnic acid, vulpinic acid and pinastric acid, increased the photoprotective activity. At the same time, they were found not cytotoxic on keratinocyte cell lines and photostable in the UVA and UVB ranges. Thus, lichens represent an attractive source to find good candidate ingredients as photoprotective agents. Additionally, the uncommon scalemic usnic acid mixture in this Vulpicida species was proven through electronic circular dichroism calculation. Full article

(This article belongs to the Special Issue Lichens: Chemistry, Ecological and Biological Activities)

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Myrcia splendens (Sw.) DC. (syn. M. fallax (Rich.) DC.) (Myrtaceae) Essential Oil from Amazonian Ecuador: A Chemical Characterization and Bioactivity Profile

by Laura Scalvenzi^1,*, Alessandro Grandini², Antonella Spagnoletti², Massimo Tacchini²

, David Neill³, José Luis Ballesteros⁴

, Gianni Sacchetti²

and Alessandra Guerrini^2,3,*

¹ Department of Earth Science, Universidad Estatal Amazónica, Puyo 160106, Ecuador

² Department of Life Sciences and Biotechnology (SVeB), UR7 Terra&Acqua Tech, University of Ferrara, Ferrara 44121, Italy

³ Department of Life Science, Universidad Estatal Amazónica, Puyo 160106, Ecuador

⁴ Department of Life Sciences, Universidad Politécnica Salesiana, Quito 170525, Ecuador

Molecules 2017, 22(7), 1163; https://doi.org/10.3390/molecules22071163 - 12 Jul 2017

Cited by 31 | Viewed by 6378

Abstract

In this study, we performed the chemical characterization of Myrcia splendens (Sw.) DC. (Myrtaceae) essential oil from Amazonian Ecuador and the assessment of its bioactivity in terms of cytotoxic, antibacterial, and antioxidant activity as starting point for possible applicative uses. M. splendens essential [...] Read more.

In this study, we performed the chemical characterization of Myrcia splendens (Sw.) DC. (Myrtaceae) essential oil from Amazonian Ecuador and the assessment of its bioactivity in terms of cytotoxic, antibacterial, and antioxidant activity as starting point for possible applicative uses. M. splendens essential oil, obtained by hydro-distillation, was analyzed by Gas Chromatography-Mass Spectrometry (GC-MS) and Gas Chromatography-Flame Ionization Detector (GC-FID): the major components were found to be trans-nerolidol (67.81%) and α-bisabolol (17.51%). Furthermore, we assessed the cytotoxic activity against MCF-7 (breast), A549 (lung) human tumor cell lines, and HaCaT (human keratinocytes) non-tumor cell line through 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) test: promising results in terms of selectivity and efficacy against the MCF-7 cell line (IC₅₀ of 5.59 ± 0.13 μg/mL at 48 h) were obtained, mainly due to α-bisabolol. Furthermore, antibacterial activity against Gram positive and negative bacteria were performed through High Performance Thin Layer Chromatography (HPTLC) bioautographic assay and microdilution method: trans-nerolidol and β-cedren-9-one were the main molecules responsible for the low antibacterial effects against human pathogens. Nevertheless, interesting values of Minimum Inhibitory Concentration (MIC) were noticeable against phytopathogen strains. Radical scavenging activity performed by HPTLC bioautographic and spectrophotometric 1,1-diphenyl-2-picrylhydrazyl (DPPH) approaches were negligible. In conclusion, the essential oil revealed a good potential for plant defense and anti-cancer applications. Full article

(This article belongs to the Special Issue Essential Oils: Chemistry and Bioactivity)

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Open AccessArticle

Extraction of Pathogenesis-Related Proteins and Phenolics in Sauvignon Blanc as Affected by Grape Harvesting and Processing Conditions

by Bin Tian^1,*

, Roland Harrison¹, James Morton¹

, Marlene Jaspers¹, Simon Hodge¹

, Claire Grose² and Mike Trought²

¹ Faculty of Agriculture and Life Sciences, Lincoln University, Lincoln 7647, New Zealand

² Marlborough Research Centre, New Zealand Institute for Plant and Food Research Ltd., Blenheim 7240, New Zealand

Molecules 2017, 22(7), 1164; https://doi.org/10.3390/molecules22071164 - 12 Jul 2017

Cited by 18 | Viewed by 6187

Abstract

Thaumatin-like proteins (TLPs) and chitinases are the two main groups of pathogenesis-related (PR) proteins found in wine that cause protein haze formation. Previous studies have found that phenolics are also involved in protein haze formation. In this study, Sauvignon Blanc grapes were harvested [...] Read more.

Thaumatin-like proteins (TLPs) and chitinases are the two main groups of pathogenesis-related (PR) proteins found in wine that cause protein haze formation. Previous studies have found that phenolics are also involved in protein haze formation. In this study, Sauvignon Blanc grapes were harvested and processed in two vintages (2011 and 2012) by three different treatments: (1) hand harvesting with whole bunch press (H-WB); (2) hand harvesting with destem/crush and 3 h skin contact (H-DC-3); and (3) machine harvesting with destem/crush and 3 h skin contact (M-DC-3). The juices were collected at three pressure levels (0.4 MPa, 0.8 MPa and 1.6 MPa), some juices were fermented in 750 mL of wine bottles to determine the bentonite requirement for the resulting wines. Results showed juices of M-DC-3 had significantly lower concentration of proteins, including PR proteins, compared to those of H-DC-3, likely due to the greater juice yield of M-DC-3 and interactions between proteins and phenolics. Juices from the 0.8–1.6 MPa pressure and resultant wines had the highest concentration of phenolics but the lowest concentration of TLPs. This supported the view that TLPs are released at low pressure as they are mainly present in grape pulp but additional extraction of phenolics largely present in skin occurs at higher pressing pressure. Wine protein stability tests showed a positive linear correlation between bentonite requirement and the concentration of chitinases, indicating the possibility of predicting bentonite requirement by quantification of chitinases. This study contributes to an improved understanding of extraction of haze-forming PR proteins and phenolics that can influence bentonite requirement for protein stabilization. Full article

(This article belongs to the Collection Wine Chemistry)

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Open AccessArticle

Role of the p-Coumaroyl Moiety in the Antioxidant and Cytoprotective Effects of Flavonoid Glycosides: Comparison of Astragalin and Tiliroside

by Xican Li^1,2,*

, Yage Tian³, Tingting Wang^1,2, Qiaoqi Lin¹, Xiaoyi Feng¹, Qian Jiang^1,2, Yamei Liu³ and Dongfeng Chen^3,*

¹ School of Chinese Herbal Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, China

² Innovative Research & Development Laboratory of TCM, Guangzhou University of Chinese Medicine, Guangzhou 510006, China

³ School of Basic Medical Science & Research Center of Basic Integrative Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, China

Molecules 2017, 22(7), 1165; https://doi.org/10.3390/molecules22071165 - 12 Jul 2017

Cited by 41 | Viewed by 6724

Abstract

The aim of this study was to explore the role of p-coumaroyl in the antioxidant and cytoprotective effects of flavonoid glycosides. The antioxidant effects of astragalin and tiliroside were compared using ferric ion reducing antioxidant power, DPPH• scavenging, ABTS•⁺ scavenging, •O [...] Read more.

The aim of this study was to explore the role of p-coumaroyl in the antioxidant and cytoprotective effects of flavonoid glycosides. The antioxidant effects of astragalin and tiliroside were compared using ferric ion reducing antioxidant power, DPPH• scavenging, ABTS•⁺ scavenging, •O₂^– scavenging, and Fe²⁺-chelating assays. The results of these assays revealed that astragalin and tiliroside both exhibited dose-dependent activities; however, tiliroside exhibited lower IC₅₀ values than astragalin. In the Fe²⁺-chelating assay, tiliroside gave a larger shoulder-peak at 510 nm than astragalin, and was also found to be darker in color. Both of these compounds were subsequently evaluated in a Fenton-induced mesenchymal stem cell (MSC) damaged assay, where tiliroside performed more effectively as a cytoprotective agent than astragalin. Tiliroside bearing a 6′′-O-p-coumaroyl moiety exhibits higher antioxidant and cytoprotective effects than astragalin. The 6′′-O-p-coumaroyl moiety of tiliroside not only enhances the possibility of electron-transfer and hydrogen-atom-transfer-based multi-pathways, but also enhances the likelihood of Fe-chelating. The p-coumaroylation of the 6"-OH position could therefore be regarded as a potential approach for improving the antioxidant and cytoprotective effects of flavonoid glycosides in MSC implantation therapy. Full article

(This article belongs to the Special Issue New Methodologies in Natural Product Analytics and Structure Elucidation)

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A New N-methoxypyridone from the Co-Cultivation of Hawaiian Endophytic Fungi Camporesia sambuci FT1061 and Epicoccum sorghinum FT1062

by Chunshun Li^1,2, Ariel M. Sarotti³

, Baojun Yang², James Turkson² and Shugeng Cao^1,2,*

¹ Department of Pharmaceutical Sciences, Daniel K. Inouye College of Pharmacy, University of Hawai’i at Hilo, 200 West Kawili Street, Hilo, HI 96720, USA

² Cancer Biology Program, University of Hawaii Cancer Center, 701 Ilalo Street, Honolulu, HI 96813, USA

³ Instituto de Química Rosario (CONICET), Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 531, Rosario 2000, Argentina

Molecules 2017, 22(7), 1166; https://doi.org/10.3390/molecules22071166 - 12 Jul 2017

Cited by 29 | Viewed by 5910

Abstract

A new N-methoxypyridone analog (1), together with four known compounds, was isolated from the co-culture of Hawaiian endophytic fungi Camporesia sambuci FT1061 and Epicoccum sorghinum FT1062. The structure of the new compound was elucidated as 11S-hydroxy-1-methoxyfusaricide (1 [...] Read more.

A new N-methoxypyridone analog (1), together with four known compounds, was isolated from the co-culture of Hawaiian endophytic fungi Camporesia sambuci FT1061 and Epicoccum sorghinum FT1062. The structure of the new compound was elucidated as 11S-hydroxy-1-methoxyfusaricide (1) by extensive spectroscopic analysis and comparison with the literature. The absolute configuration of 1 was determined by comparison with the experimental and calculated ECD spectra. The absolute configuration of compound 3 was investigated and renamed as (+)-epipyridone by comparison of the optical rotation and CD spectrum with those of 1. The other known compounds were identified as epicoccarine B (2), D8646-2-6 (4), and iso-D8646-2-6 (5). Compounds 4 and 5 showed modest inhibitory activity towards pathogenic fungi. Epicoccarine B (2) inhibited A2780 and TK-10 with an IC₅₀ value of 22 μM. Full article

(This article belongs to the Special Issue Special Issue in Honor of Professor Thomas James Simpson on the Occasion of His 70th Birthday)

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Open AccessArticle

Structure-Activity Relationships of Acyclic Selenopurine Nucleosides as Antiviral Agents

by Pramod K. Sahu^†, Tamima Umme^†, Jinha Yu, Gyudong Kim, Shuhao Qu, Siddhi D. Naik and Lak Shin Jeong^*

¹ Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 08826, Korea

^† The authors contributed equally to this work.

Molecules 2017, 22(7), 1167; https://doi.org/10.3390/molecules22071167 - 12 Jul 2017

Cited by 8 | Viewed by 6569

Abstract

A series of acyclic selenopurine nucleosides 3a–f and 4a–g were synthesized based on the bioisosteric rationale between oxygen and selenium, and then evaluated for antiviral activity. Among the compounds tested, seleno-acyclovir (4a) exhibited the most potent anti-herpes [...] Read more.

A series of acyclic selenopurine nucleosides 3a–f and 4a–g were synthesized based on the bioisosteric rationale between oxygen and selenium, and then evaluated for antiviral activity. Among the compounds tested, seleno-acyclovir (4a) exhibited the most potent anti-herpes simplex virus (HSV)-1 (EC₅₀ = 1.47 µM) and HSV-2 (EC₅₀ = 6.34 µM) activities without cytotoxicity up to 100 µM, while 2,6-diaminopurine derivatives 4e–g exhibited significant anti-human cytomegalovirus (HCMV) activity, which is slightly more potent than the guanine derivative 4d, indicating that they might act as prodrugs of seleno-ganciclovir (4d). Full article

(This article belongs to the Special Issue Nucleic Acid Chemistry and Nucleic Acid Drugs: A Themed Issue in Honor of Professor Lihe Zhang on the Occasion of His 80th Birthday)

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Open AccessArticle

Isolation and Characterization of Aphidicolin Derivatives from Tolypocladium inflatum

by Jie Lin^1,†, Shubin Niu^2,†, Zhengfeng Ding¹, Renlei Wang¹, Qun Dai¹, Wei Wei¹, Rongrong Luo¹ and Ling Liu^3,*

¹ Jiangsu Key Laboratory for Biofunctional Molecules, College of Life Science and Chemistry,Jiangsu Second Normal University, Nanjing 210003, China

² School of Biomedicine, Beijing City University, Beijing 100083, China

³ State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China

^† These authors contributed equally to this work.

Molecules 2017, 22(7), 1168; https://doi.org/10.3390/molecules22071168 - 12 Jul 2017

Cited by 11 | Viewed by 5072

Abstract

Inflatin G (1), a new aphidicolin analogue, together with seven known compounds inflatin A (2), inflatin B (3), aphidicolin (4), aphidicolin-17-monoacetate (5), gulypyrone A (6), pyridoxatin rotamers A (7) [...] Read more.

Inflatin G (1), a new aphidicolin analogue, together with seven known compounds inflatin A (2), inflatin B (3), aphidicolin (4), aphidicolin-17-monoacetate (5), gulypyrone A (6), pyridoxatin rotamers A (7) and B (8), were isolated from the ascomycete fungus Tolypocladium inflatum. Their structures were determined through NMR analyses and the circular dichroism data of the in situ formed [Rh₂(OCOCF₃)₄] complexes. Compounds 1, 4, 5, 7, and 8 showed modest cytotoxicity against four human cancer cell lines A549, CNE1-MP1, A375, and MCF-7. Full article

(This article belongs to the Collection Bioactive Compounds)

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Open AccessReview

Co-Transcriptional Folding and Regulation Mechanisms of Riboswitches

by Sha Gong¹, Yanli Wang², Zhen Wang² and Wenbing Zhang^2,*

¹ Hubei Key Laboratory of Economic Forest Germplasm Improvement and Resources Comprehensive Utilization, Hubei Collaborative Innovation Center for the Characteristic Resources Exploitation of Dabie Mountains, Huanggang Normal University, Huanggang 438000, Hubei, China

² Department of Physics, Wuhan University, Wuhan 430072, Hubei, China

Molecules 2017, 22(7), 1169; https://doi.org/10.3390/molecules22071169 - 13 Jul 2017

Cited by 18 | Viewed by 6892

Abstract

Riboswitches are genetic control elements within non-coding regions of mRNA. These self-regulatory elements have been found to sense a range of small metabolites, ions, and other physical signals to exert regulatory control of transcription, translation, and splicing. To date, more than a dozen [...] Read more.

Riboswitches are genetic control elements within non-coding regions of mRNA. These self-regulatory elements have been found to sense a range of small metabolites, ions, and other physical signals to exert regulatory control of transcription, translation, and splicing. To date, more than a dozen riboswitch classes have been characterized that vary widely in size and secondary structure. Extensive experiments and theoretical studies have made great strides in understanding the general structures, genetic mechanisms, and regulatory activities of individual riboswitches. As the ligand-dependent co-transcriptional folding and unfolding dynamics of riboswitches are the key determinant of gene expression, it is important to investigate the thermodynamics and kinetics of riboswitches both in the presence and absence of metabolites under the transcription. This review will provide a brief summary of the studies about the regulation mechanisms of the pbuE, S_MK, yitJ, and metF riboswitches based on the ligand-dependent co-transcriptional folding of the riboswitches. Full article

(This article belongs to the Section Bioorganic Chemistry)

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Development of Antimicrobial Packaging Film Made from Poly(Lactic Acid) Incorporating Titanium Dioxide and Silver Nanoparticles

by Wenhui Li¹

, Cheng Zhang¹, Hai Chi¹, Lin Li², Tianqing Lan¹, Peng Han¹, Haiyan Chen¹ and Yuyue Qin^1,*

¹ Institute of Yunnan Food Safety, Kunming University of Science and Technology, Kunming 650550, China

² College of Light Industry and Food Science, South China University of Technology, Guangzhou 510640, China

Molecules 2017, 22(7), 1170; https://doi.org/10.3390/molecules22071170 - 13 Jul 2017

Cited by 131 | Viewed by 9545

Abstract

Polylactide (PLA)/nano-TiO₂ and PLA/nano-TiO₂/nano-Ag blends films were prepared by a solvent volatilization method. Compared to pure PLA film, the nano-blend films have low water vapor permeability (WVP) and a poor transparency. With the increase of the NPs in the PLA, [...] Read more.

Polylactide (PLA)/nano-TiO₂ and PLA/nano-TiO₂/nano-Ag blends films were prepared by a solvent volatilization method. Compared to pure PLA film, the nano-blend films have low water vapor permeability (WVP) and a poor transparency. With the increase of the NPs in the PLA, the tensile strength (TS) and elastic modulus (EM) decreased, while the elongation at break (ε) increased. SEM analysis indicated a rougher cross-section of the nano-blend films. According to the FTIR analysis, no new chemical bonds were formed in the nano-blend films. By using DSC to examine the crystallization and melting behavior, the result shows that the NPs have no effect on the glass transition (T_g) and melting temperature (T_m), but they caused an increase on the cold crystallization (T_c) and crystallinity (X_c). TGA results show that the addition of nanoparticles significantly improved the thermal stability. The PLA nano-blend films show a good antimicrobial activity against. E. coli and Listeria monocytogenes. Most important, we carried out migration tests, and verified that the release of NPs from the nano-blend films was within the standard limits. Full article

(This article belongs to the Special Issue Biomedical Applications of Polylactide (PLA) and its Copolymers)

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Synthesis and In Vitro Antimycobacterial and Antibacterial Activity of 8-OMe Ciprofloxacin-Hydrozone/Azole Hybrids

by Zhi Xu^1,2, Shu Zhang³, Lian-Shun Feng², Xiao-Ning Li², Guo-Cheng Huang^1,2, Yun Chai², Zao-Sheng Lv^1,*, Hui-Yuan Guo² and Ming-Liang Liu^2,*

¹ Key Laboratory of Hubei Province for Coal Conversion and New Carbon Materials, Wuhan University of Science and Technology, Wuhan 430081, China

² Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China

³ Pony Testing International Group (Wuhan), Wuhan 430000, China

Molecules 2017, 22(7), 1171; https://doi.org/10.3390/molecules22071171 - 13 Jul 2017

Cited by 32 | Viewed by 5156

Abstract

A series of novel 8-OMe ciprofloxacin (CPFX)-hydrazone/azole hybrids were designed, synthesized, and evaluated for their in vitro biological activities. Our results reveal that all of the hydrozone-containing hybrids (except for 7) show potency against Mycobacterium tuberculosis (MTB) H₃₇Rv (minimum inhibitory [...] Read more.

A series of novel 8-OMe ciprofloxacin (CPFX)-hydrazone/azole hybrids were designed, synthesized, and evaluated for their in vitro biological activities. Our results reveal that all of the hydrozone-containing hybrids (except for 7) show potency against Mycobacterium tuberculosis (MTB) H₃₇Rv (minimum inhibitory concentration (MIC): <0.5 μM), which is better than the parent drug CPFX, and comparable to moxifloxacin and isoniazid, some of the tested Gram-positive strains (MIC: 0.06–4 μg/mL), and most Gram-negative strains (MIC: ≤0.03–4 μg/mL). Full article

(This article belongs to the Section Medicinal Chemistry)

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Facile Synthesis of Novel Coumarin Derivatives, Antimicrobial Analysis, Enzyme Assay, Docking Study, ADMET Prediction and Toxicity Study

by Shailee V. Tiwari¹, Julio A. Seijas²

, Maria Pilar Vazquez-Tato², Aniket P. Sarkate³, Kshipra S. Karnik³ and Anna Pratima G. Nikalje^1,*

¹ Y. B. Chavan College of Pharmacy, Dr. Rafiq Zakaria Campus, Rauza Bagh, Aurangabad 431001, India

² Departamento de Química Orgánica, Facultad de Ciencias, Universidad of Santiago De Compostela, Alfonso X el Sabio, Lugo 27002, Spain

³ Department of Chemical Technology, Dr. Babasaheb Ambedkar Marathwada University, Aurangabad 431004, India

Molecules 2017, 22(7), 1172; https://doi.org/10.3390/molecules22071172 - 13 Jul 2017

Cited by 36 | Viewed by 5821

Abstract

The work reports the synthesis under solvent-free condition using the ionic liquid [Et₃NH][HSO₄] as a catalyst of fifteen novel 3-((dicyclohexylamino)(substituted phenyl/heteryl)-methyl)-4-hydroxy-2H-chromen-2-onederivatives 4a–o as potential antimicrobial agents. The structures of the synthesized compounds were confirmed by [...] Read more.

The work reports the synthesis under solvent-free condition using the ionic liquid [Et₃NH][HSO₄] as a catalyst of fifteen novel 3-((dicyclohexylamino)(substituted phenyl/heteryl)-methyl)-4-hydroxy-2H-chromen-2-onederivatives 4a–o as potential antimicrobial agents. The structures of the synthesized compounds were confirmed by IR, ¹H-NMR, ¹³C-NMR, mass spectral studies and elemental analyses. All the synthesized compounds were evaluated for their in vitro antifungal and antibacterial activity. The compound 4k bearing 4-hydroxy-3-ethoxy group on the phenyl ring was found to be the most active antifungal agent. The compound 4e bearing a 2,4-difluoro group on the phenyl ring was found to be the most active antibacterial agent. The mode of action of the most promising antifungal compound 4k was established by an ergosterol extraction and quantitation assay. From the assay it was found that 4k acts by inhibition of ergosterol biosynthesis in C. albicans. Molecular docking studies revealed a highly spontaneous binding ability of the tested compounds to the active site of lanosterol 14α-demethylase, which suggests that the tested compounds inhibit the synthesis of this enzyme. The synthesized compounds were analyzed for in silico ADMET properties to establish oral drug like behavior and showed satisfactory results. To establish the antimicrobial selectivity and safety, the most active compounds 4e and 4k were further tested for cytotoxicity against human cancer cell line HeLa and were found to be non-cytotoxic in nature. An in vivo acute oral toxicity study was also performed for the most active compounds 4e and 4k and results indicated that the compounds are non-toxic. Full article

(This article belongs to the Special Issue ECSOC-20)

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Open AccessReview

Novel Applications of Metabolomics in Personalized Medicine: A Mini-Review

by Bingbing Li¹, Xuyun He¹, Wei Jia^2,3,* and Houkai Li^1,*

¹ Center for Traditional Chinese Medicine and Systems Biology, Institute for Interdisciplinary Medicine Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China

² Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI 96813, USA

³ Center for Translational Medicine, and Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai 200233, China

Molecules 2017, 22(7), 1173; https://doi.org/10.3390/molecules22071173 - 13 Jul 2017

Cited by 81 | Viewed by 9920

Abstract

Interindividual variability in drug responses and disease susceptibility is common in the clinic. Currently, personalized medicine is highly valued, the idea being to prescribe the right medicine to the right patient. Metabolomics has been increasingly applied in evaluating the therapeutic outcomes of clinical [...] Read more.

Interindividual variability in drug responses and disease susceptibility is common in the clinic. Currently, personalized medicine is highly valued, the idea being to prescribe the right medicine to the right patient. Metabolomics has been increasingly applied in evaluating the therapeutic outcomes of clinical drugs by correlating the baseline metabolic profiles of patients with their responses, i.e., pharmacometabonomics, as well as prediction of disease susceptibility among population in advance, i.e., patient stratification. The accelerated advance in metabolomics technology pinpoints the huge potential of its application in personalized medicine. In current review, we discussed the novel applications of metabolomics with typical examples in evaluating drug therapy and patient stratification, and underlined the potential of metabolomics in personalized medicine in the future. Full article

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Open AccessArticle

Ultrafast Dynamics of Sb-Corroles: A Combined Vis-Pump Supercontinuum Probe and Broadband Fluorescence Up-Conversion Study

by Clark Zahn¹, Till Stensitzki¹

, Mario Gerecke², Alexander Berg³, Atif Mahammed⁴, Zeev Gross⁴ and Karsten Heyne^1,*

¹ Department of Physics, Free University Berlin, Arnimallee 14, D-14195 Berlin, Germany

² Department of Chemistry, Humboldt-Universität zu Berlin, Brook-Taylor-Str. 2, D-12489 Berlin, Germany

³ Institute of Chemistry, The Hebrew University of Jerusalem, Jerusalem 91904, Israel

⁴ Schulich Faculty of Chemistry, Technion-Israel Institute of Technology, Haifa 3200008, Israel

Molecules 2017, 22(7), 1174; https://doi.org/10.3390/molecules22071174 - 13 Jul 2017

Cited by 19 | Viewed by 5858

Abstract

Corroles are a developing class of tetrapyrrole-based molecules with significant chemical potential and relatively unexplored photophysical properties. We combined femtosecond broadband fluorescence up-conversion and fs broadband Vis-pump Vis-probe spectroscopy to comprehensively characterize the photoreaction of 5,10,15-tris-pentafluorophenyl-corrolato-antimony(V)-trans-difluoride (Sb-tpfc-F₂). Upon fs [...] Read more.

Corroles are a developing class of tetrapyrrole-based molecules with significant chemical potential and relatively unexplored photophysical properties. We combined femtosecond broadband fluorescence up-conversion and fs broadband Vis-pump Vis-probe spectroscopy to comprehensively characterize the photoreaction of 5,10,15-tris-pentafluorophenyl-corrolato-antimony(V)-trans-difluoride (Sb-tpfc-F₂). Upon fs Soret band excitation at ~400 nm, the energy relaxed almost completely to Q band electronic excited states with a time constant of 500 ± 100 fs; this is evident from the decay of Soret band fluorescence at around 430 nm and the rise time of Q band fluorescence, as well as from Q band stimulated emission signals at 600 and 650 nm with the same time constant. Relaxation processes on a time scale of 10 and 20 ps were observed in the fluorescence and absorption signals. Triplet formation showed a time constant of 400 ps, with an intersystem crossing yield from the Q band to the triplet manifold of between 95% and 99%. This efficient triplet formation is due to the spin-orbit coupling of the antimony ion. Full article

(This article belongs to the Special Issue Porphyrins and Phthalocyanines: Synthesis, Properties and Applications)

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Open AccessArticle

Evodiamine Exerts an Anti-Hepatocellular Carcinoma Activity through a WWOX-Dependent Pathway

by Che-Yuan Hu^1,2,†, Hung-Tsung Wu^3,4,†, Yu-Chu Su^3,5,6, Ching-Han Lin^1,7, Chih-Jen Chang^4,* and Chao-Liang Wu^1,6,*

¹ Graduate Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan

² Department of Urology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan

³ Research Center of Clinical Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan

⁴ Department of Family Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan

⁵ Department of Otolaryngology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan

⁶ Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan

⁷ Division of Endocrinology and Metabolism, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan

^† Che-Yuan Hu and Hung-Tsung Wu contribute equally to this work.

Molecules 2017, 22(7), 1175; https://doi.org/10.3390/molecules22071175 - 14 Jul 2017

Cited by 38 | Viewed by 4851

Abstract

Evodiamine is one of the main components isolated from Evodia rutaecarpa, and it has been reported to exert inhibitory effects on cancers by anti-proliferative and apoptosis-inducing activities. Although the anti-cancer activity of evodiamine has been identified, the precise mechanisms of this action [...] Read more.

Evodiamine is one of the main components isolated from Evodia rutaecarpa, and it has been reported to exert inhibitory effects on cancers by anti-proliferative and apoptosis-inducing activities. Although the anti-cancer activity of evodiamine has been identified, the precise mechanisms of this action remain obscure. While previous studies indicated that evodiamine exerts anti-tumor effects through inhibiting β-catenin activity, and WW domain-containing oxidoreductase (WWOX) regulates β-catenin accumulation in cytoplasm, the effects of evodiamine on the expression of WWOX are still unknown. In this study, we provide evidence that evodiamine dose- and time-dependently inhibits both Mus musculus and Homo sapiens hepatocellular carcinoma (HCC) cells, as well as Hepa1-6 and HepG2 cell proliferation. We further tested the therapeutic effects of evodiamine in Hepa1-6 hepatoma-bearing mice, and we found that treatment of evodiamine by oral gavage significantly decreased the tumor size of the mice. Moreover, the expressions of WWOX were dose-dependently increased in HCC cell lines as well as in Hepa1-6 hepatoma-bearing mice after the treatment with evodiamine. Knockdown of WWOX in HepG2 and Hepa1-6 cells diminished the effects of evodiamine on the inhibitory effect of cancer cell growth, indicating that evodiamine induced anti-cancer activity through a WWOX-dependent pathway. As such, evodiamine activated WWOX to exert an anti-HCC activity, and might be a potential therapeutic or preventive candidate for HCC treatment. Full article

(This article belongs to the Special Issue Herbal Remedies Meet Modern Day Medicine: Challenges and Opportunities)

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Open AccessFeature PaperReview

The Exact Nuclear Overhauser Enhancement: Recent Advances

by Parker J. Nichols¹, Alexandra Born¹, Morkos A. Henen^1,2

, Dean Strotz³, Julien Orts³

, Simon Olsson⁴, Peter Güntert^3,5,6, Celestine N. Chi⁷ and Beat Vögeli^1,*

¹ Department of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, 12801 East 17th Avenue, Aurora, CO 80045, USA

² Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt

³ Laboratory of Physical Chemistry, ETH Zürich, ETH-Hönggerberg, Zürich 8093, Switzerland

⁴ Department of Mathematics and Computer Science, Freie Universität Berlin, Arnimallee 6, Berlin 14195, Germany

⁵ Institute of Biophysical Chemistry, Center for Biomolecular Magnetic Resonance, Goethe University Frankfurt am Main, Frankfurt am Main 60438, Germany

⁶ Graduate School of Science, Tokyo Metropolitan University, Hachioji, Tokyo 192-0397, Japan

⁷ Department of Medical Biochemistry and Microbiology, Uppsala University, BMC Box 582, Uppsala SE-75123, Sweden

Molecules 2017, 22(7), 1176; https://doi.org/10.3390/molecules22071176 - 14 Jul 2017

Cited by 21 | Viewed by 6669

Abstract

Although often depicted as rigid structures, proteins are highly dynamic systems, whose motions are essential to their functions. Despite this, it is difficult to investigate protein dynamics due to the rapid timescale at which they sample their conformational space, leading most NMR-determined structures [...] Read more.

Although often depicted as rigid structures, proteins are highly dynamic systems, whose motions are essential to their functions. Despite this, it is difficult to investigate protein dynamics due to the rapid timescale at which they sample their conformational space, leading most NMR-determined structures to represent only an averaged snapshot of the dynamic picture. While NMR relaxation measurements can help to determine local dynamics, it is difficult to detect translational or concerted motion, and only recently have significant advances been made to make it possible to acquire a more holistic representation of the dynamics and structural landscapes of proteins. Here, we briefly revisit our most recent progress in the theory and use of exact nuclear Overhauser enhancements (eNOEs) for the calculation of structural ensembles that describe their conformational space. New developments are primarily targeted at increasing the number and improving the quality of extracted eNOE distance restraints, such that the multi-state structure calculation can be applied to proteins of higher molecular weights. We then review the implications of the exact NOE to the protein dynamics and function of cyclophilin A and the WW domain of Pin1, and finally discuss our current research and future directions. Full article

(This article belongs to the Special Issue Recent Advances in Biomolecular NMR Spectroscopy)

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Open AccessFeature PaperReview

Solar or UVA-Visible Photocatalytic Ozonation of Water Contaminants

by Fernando J. Beltrán^* and Ana Rey

Departamento de Ingeniería Química y Química Física, Instituto Universitario de Investigación del Agua, Cambio Climático y Sostenibilidad, Universidad de Extremadura, Av. Elvas s/n, 06006 Badajoz, Spain

Molecules 2017, 22(7), 1177; https://doi.org/10.3390/molecules22071177 - 14 Jul 2017

Cited by 37 | Viewed by 5762

Abstract

An incipient advanced oxidation process, solar photocatalytic ozonation (SPO), is reviewed in this paper with the aim of clarifying the importance of this process as a more sustainable water technology to remove priority or emerging contaminants from water. The synergism between ozonation and [...] Read more.

An incipient advanced oxidation process, solar photocatalytic ozonation (SPO), is reviewed in this paper with the aim of clarifying the importance of this process as a more sustainable water technology to remove priority or emerging contaminants from water. The synergism between ozonation and photocatalytic oxidation is well known to increase the oxidation rate of water contaminants, but this has mainly been studied in photocatalytic ozonation systems with lamps of different radiation wavelength, especially of ultraviolet nature (UVC, UVB, UVA). Nowadays, process sustainability is critical in environmental technologies including water treatment and reuse; the application of SPO systems falls into this category, and contributes to saving energy and water. In this review, we summarized works published on photocatalytic ozonation where the radiation source is the Sun or simulated solar light, specifically, lamps emitting radiation to cover the UVA and visible light spectra. The main aspects of the review include photoreactors used and radiation sources applied, synthesis and characterization of catalysts applied, influence of main process variables (ozone, catalyst, and pollutant concentrations, light intensity), type of water, biodegradability and ecotoxicity, mechanism and kinetics, and finally catalyst activity and stability. Full article

(This article belongs to the Special Issue Photon-involving Purification of Water and Air)

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Open AccessArticle

Metal-Free Regiodivergent Addition of Carbon Nucleophiles to α,β-Unsaturated Electrophiles

by Cédric Spitz^*, Alain G. Giuglio-Tonolo, Thierry Terme and Patrice Vanelle^*

Aix-Marseille University, CNRS, ICR UMR 7273, Equipe Pharmaco-Chimie Radicalaire, Faculté de Pharmacie, 27 Boulevard Jean Moulin, CS 30064, 13385 Marseille CEDEX 05, France

Molecules 2017, 22(7), 1178; https://doi.org/10.3390/molecules22071178 - 14 Jul 2017

Cited by 1 | Viewed by 3640

Abstract

A mild and metal-free regiodivergent addition of carbon nucleophiles to α,β-unsaturated electrophiles was developed. Total 1,2-regioselectivity was observed in the addition of nitrobenzyl chloride derivative 1 to α,β-unsaturated aldehydes 2 in the presence of TDAE. Moreover, the reaction between p-nitrobenzyl chloride 1a [...] Read more.

A mild and metal-free regiodivergent addition of carbon nucleophiles to α,β-unsaturated electrophiles was developed. Total 1,2-regioselectivity was observed in the addition of nitrobenzyl chloride derivative 1 to α,β-unsaturated aldehydes 2 in the presence of TDAE. Moreover, the reaction between p-nitrobenzyl chloride 1a and α,β-unsaturated iminium salts 4 led to the formation of the 1,4-adduct with total regioselectivity. Full article

(This article belongs to the Section Organic Chemistry)

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Open AccessFeature PaperReview

Functionalization of Endohedral Metallofullerenes with Reactive Silicon and Germanium Compounds

by Masahiro Kako^1,*, Shigeru Nagase^2,* and Takeshi Akasaka^3,4,5,6,*

¹ Department of Engineering Science, The University of Electro-Communications, Chofu 182-8585, Japan

² Fukui Institute for Fundamental Chemistry, Kyoto University, Kyoto 606-8103, Japan

³ Life Science Center of Tsukuba Advanced Research Alliance, University of Tsukuba, Ibaraki 305-8577, Japan

⁴ Department of Chemistry, Tokyo Gakugei University, Tokyo 184-8501, Japan

⁵ Foundation for Advancement of International Science, Ibaraki 305-0821, Japan

⁶ School of Materials Science and Engineering, Huazhong University of Science and Technology, Wuhan 430074, China

Molecules 2017, 22(7), 1179; https://doi.org/10.3390/molecules22071179 - 14 Jul 2017

Cited by 10 | Viewed by 5392

Abstract

Exohedral derivatization of endohedral metallofullerenes (EMFs) has been exploited as a useful method for characterizing the structural and chemical properties of EMFs, and for functionalizing them for potential applications. The introduction of heteroatoms, such as electropositive silicon atoms, to fullerene cages is a [...] Read more.

Exohedral derivatization of endohedral metallofullerenes (EMFs) has been exploited as a useful method for characterizing the structural and chemical properties of EMFs, and for functionalizing them for potential applications. The introduction of heteroatoms, such as electropositive silicon atoms, to fullerene cages is a novel functionalization method that remarkably affects the electronic characteristics of fullerenes. This review comprehensively describes the results of the reactions of monometallofullerene, dimetallofullerene, and trimetallic nitride template EMFs with disilirane, silirane, silylene, and digermirane, which afforded the corresponding silylated and germylated fullerenes. Several examples emphasize that exohedral functionalization regulates the dynamic behaviors of the encapsulated metal atoms and clusters in the fullerene cages. The electronic effects of silyl and germyl groups are represented by comparing the redox properties of silylated and germylated EMFs with those of other EMFs derivatized with carbon-atom-based functional groups. Full article

(This article belongs to the Special Issue Endohedral Metallofullerenes)

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Open AccessArticle

Resveratrol Improves Glycemic Control in Type 2 Diabetic Obese Mice by Regulating Glucose Transporter Expression in Skeletal Muscle and Liver

by Caio Y. Yonamine, Erika Pinheiro-Machado, Maria L. Michalani, Ana B. Alves-Wagner, João V. Esteves, Helayne S. Freitas and Ubiratan F. Machado^*

Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil. Av. Prof. Lineu Prestes 1524, São Paulo 05508-900, Brazil

Molecules 2017, 22(7), 1180; https://doi.org/10.3390/molecules22071180 - 14 Jul 2017

Cited by 48 | Viewed by 8520

Abstract

Insulin resistance participates in the glycaemic control disruption in type 2 diabetes mellitus (T2DM), by reducing muscle glucose influx and increasing liver glucose efflux. GLUT4 (Slc2a4 gene) and GLUT2 (Slc2a2 gene) proteins play a fundamental role in the muscle and liver [...] Read more.

Insulin resistance participates in the glycaemic control disruption in type 2 diabetes mellitus (T2DM), by reducing muscle glucose influx and increasing liver glucose efflux. GLUT4 (Slc2a4 gene) and GLUT2 (Slc2a2 gene) proteins play a fundamental role in the muscle and liver glucose fluxes, respectively. Resveratrol is a polyphenol suggested to have an insulin sensitizer effect; however, this effect, and related mechanisms, have not been clearly demonstrated in T2DM. We hypothesized that resveratrol can improve glycaemic control by restoring GLUT4 and GLUT2 expression in muscle and liver. Mice were rendered obese T2DM in adult life by neonatal injection of monosodium glutamate. Then, T2DM mice were treated with resveratrol for 60 days or not. Glycaemic homeostasis, GLUT4, GLUT2, and SIRT1 (sirtuin 1) proteins (Western blotting); Slc2a4, Slc2a2, and Pck1 (key gluconeogenic enzyme codifier) mRNAs (RT-qPCR); and hepatic glucose efflux were analysed. T2DM mice revealed: high plasma concentration of glucose, fructosamine, and insulin; insulin resistance (insulin tolerance test); decreased Slc2a4/GLUT4 content in gastrocnemius and increased Slc2a2/GLUT2 content in liver; and increased Pck1 mRNA and gluconeogenic activity (pyruvate tolerance test) in liver. All alterations were restored by resveratrol treatment. Additionally, in both muscle and liver, resveratrol increased SIRT1 nuclear content, which must participate in gene expression regulations. In sum, the results indisputably reveals that resveratrol improves glycaemic control in T2DM, and that involves an increase in muscle Slc2a4/GLUT4 and a decrease in liver Slc2a2/GLUT2 expression. This study contributes to our understanding how resveratrol might be prescribed for T2DM according to the principles of evidence-based medicine. Full article

(This article belongs to the Special Issue Plant Polyphenols as Potential Therapeutic Agents for Diabetes and Obesity)

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Open AccessArticle

Cholinesterase and Prolyl Oligopeptidase Inhibitory Activities of Alkaloids from Argemone platyceras (Papaveraceae)

by Tomáš Siatka¹, Markéta Adamcová², Lubomír Opletal², Lucie Cahlíková², Daniel Jun³, Martina Hrabinová³, Jiří Kuneš⁴ and Jakub Chlebek^2,*

¹ Department of Pharmacognosy, Faculty of Pharmacy, Charles University, Akademika Heyrovského 1203, 500 05 Hradec Králové, Czech Republic

² Department of Pharmaceutical Botany and Ecology, ADINACO Research Group, Faculty of Pharmacy, Charles University, Akademika Heyrovského 1203, 500 05 Hradec Králové, Czech Republic

³ Department of Toxicology and Military Pharmacy, Faculty of Military Health Sciences, University of Defence, Třebešská 1575, 500 01 Hradec Králové, Czech Republic

⁴ Department of Inorganic and Organic Chemistry, Faculty of Pharmacy, Charles University, Akademika Heyrovského 1203, 500 05 Hradec Králové, Czech Republic

Molecules 2017, 22(7), 1181; https://doi.org/10.3390/molecules22071181 - 14 Jul 2017

Cited by 26 | Viewed by 5136

Abstract

Alzheimer’s disease is an age-related, neurodegenerative disorder, characterized by cognitive impairment and restrictions in activities of daily living. This disease is the most common form of dementia with complex multifactorial pathological mechanisms. Many therapeutic approaches have been proposed. Among them, inhibition of acetylcholinesterase, [...] Read more.

Alzheimer’s disease is an age-related, neurodegenerative disorder, characterized by cognitive impairment and restrictions in activities of daily living. This disease is the most common form of dementia with complex multifactorial pathological mechanisms. Many therapeutic approaches have been proposed. Among them, inhibition of acetylcholinesterase, butyrylcholinesterase, and prolyl oligopeptidase can be beneficial targets in the treatment of Alzheimer’s disease. Roots, along with aerial parts of Argemone platyceras, were extracted with ethanol and fractionated on an alumina column using light petrol, chloroform and ethanol. Subsequently, repeated preparative thin-layer chromatography led to the isolation of (+)-laudanosine, protopine, (–)-argemonine, allocryptopine, (–)-platycerine, (–)-munitagine, and (–)-norargemonine belonging to pavine, protopine and benzyltetrahydroisoquinoline structural types. Chemical structures of the isolated alkaloids were elucidated by optical rotation, spectroscopic and spectrometric analysis (NMR, MS), and comparison with literature data. (+)-Laudanosine was isolated from A. platyceras for the first time. Isolated compounds were tested for human blood acetylcholinesterase, human plasma butyrylcholinesterase and recombinant prolyl oligopeptidase inhibitory activity. The alkaloids inhibited the enzymes in a dose-dependent manner. The most active compound (–)-munitagine, a pavine alkaloid, inhibited both acetylcholinesterase and prolyl oligopeptidase with IC₅₀ values of 62.3 ± 5.8 µM and 277.0 ± 31.3 µM, respectively. Full article

(This article belongs to the Section Medicinal Chemistry)

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Open AccessArticle

Crystal Structure Analysis of the First Discovered Stability-Enhanced Solid State of Tenofovir Disoproxil Free Base Using Single Crystal X-ray Diffraction

by Ji-Hun An^1,†

, Alice Nguvoko Kiyonga^1,†, Woojin Yoon², Hyung Chul Ryu³, Jae-Sun Kim³, Chaeri Kang¹, Minho Park¹, Hoseop Yun^2,* and Kiwon Jung^1,*

¹ College of Pharmacy, CHA University, Sungnam 13844, Korea

² Department of Chemistry and Energy Systems Research, Ajou University, Suwon 16499, Korea

³ R&D center, J2H Biotech, Ansan 15426, Korea

^† Both authors equally contributed to this work.

Molecules 2017, 22(7), 1182; https://doi.org/10.3390/molecules22071182 - 14 Jul 2017

Cited by 8 | Viewed by 6447

Abstract

Tenofovir disoproxil (TD), an anti-virus drug, is currently marketed under its most stable form, Form-I of Tenofovir disoproxil fumarate (TDF). However, studies regarding the properties of TD free base crystal as a promising drug as well as its crystal structure have not yet [...] Read more.

Tenofovir disoproxil (TD), an anti-virus drug, is currently marketed under its most stable form, Form-I of Tenofovir disoproxil fumarate (TDF). However, studies regarding the properties of TD free base crystal as a promising drug as well as its crystal structure have not yet been reported. This assumption was made because TD free base is not directly produced in a solid form during the manufacturing process. TD free base is first obtained in an oil form, and is then synthesized into TDF crystal. In this regard, the present study was conducted to investigate both the potentiality of TD free base to be an active pharmaceutical ingredient (API) and its crystal structure. Here, TD free base solid was produced by means of drowning-out crystallization. Next, single crystal X-ray diffraction (SXD) was employed to determine the crystal structure. Powder X-ray diffraction (PXRD) and a differential scanning calorimetry (DSC) analysis were performed to evaluate the crystal’s properties. Furthermore, experiments were carried out at 15%, 35%, 55%, 75%, and 95% relative humidity (RH) for 12 h using a hygroscopic tester to determine and to compare the hygroscopicity and stability of TD free base with TDF crystal. Additionally, experiments were conducted under accelerated (40 °C, RH 75%) and stress storage (60 °C, RH 75%) conditions for 30 days to investigate the changes in purity and the formation of dimer. In this work, we report that TD free base possesses lower hygroscopicity, and thus does not generate dimer impurity from hydrolysis. Primarily, this is attributed to the fact that TD free base is not an easily ionized salt but comprises neutral hydrophobic molecules. According to the structural properties, the improved hygroscopic property of the TD free base crystal was due to the decrease of crystal polarity owing to the intermolecular H-bonds present in TD free base rings. In addition, the solubility investigation study carried out in aqueous solution and at gastrointestinal pH revealed a similarity in TDF and TD free base solubility under the mentioned conditions. Accordingly, we could confirm the potentiality of TD free base as an active pharmaceutical ingredient. Full article

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Open AccessArticle

¹⁵N-, ¹³C- and ¹H-NMR Spectroscopy Characterization and Growth Inhibitory Potency of a Combi-Molecule Synthesized by Acetylation of an Unstable Monoalkyltriazene

by Zhor Senhaji Mouhri¹, Elliot Goodfellow¹, Steven P. Kelley², Robin S. Stein², Robin D. Rogers² and Bertrand J. Jean-Claude^1,*

¹ Cancer Drug Research Laboratory, Department of Medicine, Division of Medical Oncology, McGill University Health Center/Glen Hospital, 1001 Decarie Blvd., Montreal H4A 3J1, QC, Canada

² Department of Chemistry, McGill University, 801 Sherbrooke St. W., Montreal H3A 0B8, QC, Canada

Molecules 2017, 22(7), 1183; https://doi.org/10.3390/molecules22071183 - 19 Jul 2017

Cited by 7 | Viewed by 5225

Abstract

6-(3-Methyltriaz-1-en-1-yl)-1H-benzo[de]isoquinoline-1,3(2H)-dione referred to as EG22 (8a), is an open-chain 3-alkyl-1,2,3-triazene termed “combi-molecule” designed to inhibit poly(adenosine diphosphate ribose) polymerase (PARP) and damage DNA. To delay its hydrolysis, acetylation of N3 was required. Being a monoalkyl-1,2,3-triazene, EG22 could [...] Read more.

6-(3-Methyltriaz-1-en-1-yl)-1H-benzo[de]isoquinoline-1,3(2H)-dione referred to as EG22 (8a), is an open-chain 3-alkyl-1,2,3-triazene termed “combi-molecule” designed to inhibit poly(adenosine diphosphate ribose) polymerase (PARP) and damage DNA. To delay its hydrolysis, acetylation of N3 was required. Being a monoalkyl-1,2,3-triazene, EG22 could assume two tautomers in solution or lose nitrogen during the reaction, thereby leading to several acetylated compounds. Instead, one compound was observed and to unequivocally assign its structure, we introduced isotopically labeled reagents in its preparation, with the purpose of incorporating ¹⁵N at N2 and ¹³C in the 3-methyl group. The results showed that the 1,2,3-triazene moiety remained intact, as confirmed by ¹⁵N-NMR, coupling patterns between the ¹⁵N-labeled N2 and the ¹³C-labeled methyl group. Furthermore, we undertook heteronuclear single quantum coherence (HSQC) and heteronuclear multiple bond correlation (HMBC) experiments that permitted the detection and assignment of all four nitrogens in 6-(3-acetyl-3-methyltriaz-1-en-1-yl)-1H-benzo[de]isoquinoline-1,3(2H)-dione, referred to as ZSM02 (9a), whose structure was further confirmed by X-ray crystallography. The structure showed a remarkable coplanarity between the N-acetyltriazene and the naphtalimide moiety. Thus, we unequivocally assigned 9a as the product of the reaction and compared its growth inhibitory activity with that of its precursor, EG22. ZSM02 exhibited identical growth inhibitory profile as EG22, suggesting that it may be a prodrug of EG22. Full article

(This article belongs to the Section Medicinal Chemistry)

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Open AccessArticle

Prediction of Antimicrobial and Antioxidant Activities of Mexican Propolis by ¹H-NMR Spectroscopy and Chemometrics Data Analysis

by J. Fausto Rivero-Cruz¹

, Eduardo Rodríguez de San Miguel¹, Sergio Robles-Obregón¹, Circe C. Hernández-Espino², Blanca E. Rivero-Cruz¹, José Pedraza-Chaverri¹

and Nuria Esturau-Escofet^2,*

¹ Facultad de Química, Universidad Nacional Autónoma de México, Ciudad Universitaria, 04510 Cd. Mexico, Mexico

² Instituto de Química, Universidad Nacional Autónoma de México, Ciudad Universitaria, 04510 Cd. Mexico, Mexico

Molecules 2017, 22(7), 1184; https://doi.org/10.3390/molecules22071184 - 14 Jul 2017

Cited by 13 | Viewed by 5192

Abstract

A feasibility study to predict antimicrobial and antioxidant activity properties of propolis extracts using 700-MHz ¹H-NMR spectra and multivariate regression data analysis is presented. The study was conducted with thirty-five propolis samples to develop a rapid and reliable method for the evaluation [...] Read more.

A feasibility study to predict antimicrobial and antioxidant activity properties of propolis extracts using 700-MHz ¹H-NMR spectra and multivariate regression data analysis is presented. The study was conducted with thirty-five propolis samples to develop a rapid and reliable method for the evaluation of their quality. The extracts have been evaluated by measuring phenolic and flavonoid contents; the antioxidant activity; and the antimicrobial activity. The obtained spectral data were submitted to multivariate calibration (partial least squares (PLS) and orthogonal partial least squares (OPLS)) to correlate the relative intensity and position of NMR resonance peaks with the metabolites contents and biological activities. The developed PLS and OPLS model were successfully applied to the determination of the target properties for proof of the concept. The OPLS observed vs. predicted properties plots indicate the absence of systematic errors with determination coefficients between the ranges 0.7207 to 0.9990. Up to 86.1% of explication of variation in the spectral data and 99.9% in the measured properties were attained with 88.6% of prediction capabilities in the best case (S. mutans activity) according to the cross-validation procedure. The figures of merit of the developed PLS and OPLS methods were evaluated and compared as well. Full article

(This article belongs to the Section Natural Products Chemistry)

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Open AccessArticle

Structure Elucidation and Botanical Characterization of Diterpenes from a Specific Type of Bee Glue

by Noushin Aminimoghadamfarouj and Alireza Nematollahi^*

Faculty of Pharmacy A15, The University of Sydney, Sydney, NSW 2006, Australia

Molecules 2017, 22(7), 1185; https://doi.org/10.3390/molecules22071185 - 14 Jul 2017

Cited by 17 | Viewed by 5163

Abstract

Investigation of the single plant source bee glue type originating from Southern Australia resulted in the isolation and structure elucidation of major serrulatane diterpenes, novel 7,8,18-trihydroxyserrulat-14-ene (1), along with its oxidized product, 5,18-epoxyserrulat-14-en-7,8-dione (3) and known (18RS)-5,18-epoxyserrulat-14-en-8,18-diol [...] Read more.

Investigation of the single plant source bee glue type originating from Southern Australia resulted in the isolation and structure elucidation of major serrulatane diterpenes, novel 7,8,18-trihydroxyserrulat-14-ene (1), along with its oxidized product, 5,18-epoxyserrulat-14-en-7,8-dione (3) and known (18RS)-5,18-epoxyserrulat-14-en-8,18-diol (2). Exploration into the botanical origin revealed Myoporum insulare R. Br, as the plant source of the bee glue materials. This discovery was made through comparative analysis of the myoporum bee glue samples collected from the beehives, analyses of plant resinous exudate, and resin carried on the hind legs of bees foraging for bee glue. Full article

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Open AccessReview

Solvent Supercritical Fluid Technologies to Extract Bioactive Compounds from Natural Sources: A Review

by Kooi-Yeong Khaw

, Marie-Odile Parat

, Paul Nicholas Shaw

and James Robert Falconer^*

School of Pharmacy, Pharmacy Australia Centre of Excellence, University of Queensland, Brisbane, QLD 4102, Australia

Molecules 2017, 22(7), 1186; https://doi.org/10.3390/molecules22071186 - 14 Jul 2017

Cited by 314 | Viewed by 17901

Abstract

Supercritical fluid technologies offer a propitious method for drug discovery from natural sources. Such methods require relatively short processing times, produce extracts with little or no organic co-solvent, and are able to extract bioactive molecules whilst minimising degradation. Supercritical fluid extraction (SFE) provides [...] Read more.

Supercritical fluid technologies offer a propitious method for drug discovery from natural sources. Such methods require relatively short processing times, produce extracts with little or no organic co-solvent, and are able to extract bioactive molecules whilst minimising degradation. Supercritical fluid extraction (SFE) provides a range of benefits, as well as offering routes to overcome some of the limitations that exist with the conventional methods of extraction. Unfortunately, SFE-based methods are not without their own shortcomings; two major ones being: (1) the high establishment cost; and (2) the selective solvent nature of CO₂, i.e., that CO₂ only dissolves small non-polar molecules, although this can be viewed as a positive outcome provided bioactive molecules are extracted during solvent-based SFE. This review provides an update of SFE methods for natural products and outlines the main operating parameters for extract recovery. Selected processing considerations are presented regarding supercritical fluids and the development and application of ultrasonic-assisted SFE methods, as well as providing some of the key aspects of SFE scalability. Full article

(This article belongs to the Special Issue Sub- and Supercritical Fluids and Green Chemistry)

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Open AccessArticle

Immunomodulatory Activity of Octenyl Succinic Anhydride Modified Porang (Amorphophallus oncophyllus) Glucomannan on Mouse Macrophage-Like J774.1 Cells and Mouse Primary Peritoneal Macrophages

by Sellen Gurusmatika^1,2

, Kosuke Nishi^1,3

, Eni Harmayani², Yudi Pranoto² and Takuya Sugahara^1,3,4,*

¹ Department of Bioscience, Graduate School of Agriculture, Ehime University, Matsuyama, Ehime 790-8566, Japan

² Faculty of Agricultural Technology, Gadjah Mada University, Bulaksumur, Yogyakarta 55281, Indonesia

³ Food and Health Sciences Research Center, Ehime University, Matsuyama, Ehime 790-8566, Japan

⁴ South Ehime Fisheries Research Center, Ehime University, Ainan, Ehime 798-4292, Japan

Molecules 2017, 22(7), 1187; https://doi.org/10.3390/molecules22071187 - 15 Jul 2017

Cited by 11 | Viewed by 6944

Abstract

Porang is a local plant of Indonesia, which has a high content of glucomannan. In this study, porang glucomannan (PG) was esterified with octenyl succinic anhydride (OSA) to enhance emulsion properties to be widely used in food industry. OSA-modified PG (OSA-PG) enhanced the [...] Read more.

Porang is a local plant of Indonesia, which has a high content of glucomannan. In this study, porang glucomannan (PG) was esterified with octenyl succinic anhydride (OSA) to enhance emulsion properties to be widely used in food industry. OSA-modified PG (OSA-PG) enhanced the phagocytosis activity of macrophage-like J774.1 cells and mouse peritoneal macrophages. In addition, OSA-PG increased the production of IL-6 and TNF-α by enhancing their gene expression. Immunoblot analysis displayed that OSA-PG tended to activate both nuclear factor-κB and mitogen-activated protein kinase cascades. Treatment of OSA-PG with polymyxin B revealed that cytokine production induced by OSA-PG was not caused by endotoxin contamination. Our findings also indicated that OSA-PG activates macrophages through not only Toll-like receptor (TLR) 4, but another receptor. Overall findings suggested that OSA-PG has a potential as an immunomodulatory food factor by stimulating macrophages. Full article

(This article belongs to the Collection Bioactive Compounds)

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Open AccessReview

Signaling within Allosteric Machines: Signal Transmission Pathways Inside G Protein-Coupled Receptors

by Damian Bartuzi^1,*, Agnieszka A. Kaczor^1,2 and Dariusz Matosiuk¹

¹ Department of Synthesis and Chemical Technology of Pharmaceutical Substances with Computer Modelling Lab, Medical University of Lublin, 4A Chodźki Str., Lublin PL20093, Poland

² School of Pharmacy, University of Eastern Finland, Yliopistonranta 1, P.O. Box 1627, Kuopio FI-70211, Finland

Molecules 2017, 22(7), 1188; https://doi.org/10.3390/molecules22071188 - 15 Jul 2017

Cited by 11 | Viewed by 5546

Abstract

In recent years, our understanding of function of G protein-coupled receptors (GPCRs) has changed from a picture of simple signal relays, transmitting only a particular signal to a particular G protein heterotrimer, to versatile machines, capable of various responses to different stimuli and [...] Read more.

In recent years, our understanding of function of G protein-coupled receptors (GPCRs) has changed from a picture of simple signal relays, transmitting only a particular signal to a particular G protein heterotrimer, to versatile machines, capable of various responses to different stimuli and being modulated by various factors. Some recent reports provide not only the data on ligands/modulators and resultant signals induced by them, but also deeper insights into exact pathways of signal migration and mechanisms of signal transmission through receptor structure. Combination of these computational and experimental data sheds more light on underlying mechanisms of signal transmission and signaling bias in GPCRs. In this review we focus on available clues on allosteric pathways responsible for complex signal processing within GPCRs structures, with particular emphasis on linking compatible in silico- and in vitro-derived data on the most probable allosteric connections. Full article

(This article belongs to the Special Issue G-protein Coupled Receptor Structure and Function)

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Open AccessArticle

NMR Insights into the Structure-Function Relationships in the Binding of Melanocortin Analogues to the MC1R Receptor

by Maurício Morais^1,2, Héctor Zamora-Carreras³

, Paula D. Raposinho¹, Maria Cristina Oliveira¹, David Pantoja-Uceda³

, João D. G. Correia¹ and M. Angeles Jiménez^3,*

¹ Centro de Ciências e Tecnologias Nucleares, Instituto Superior Técnico, Universidade de Lisboa, Estrada Nacional 10 (km 139.7), 2695-066 Bobadela LRS, Portugal

² Division of Imaging Sciences and Biomedical Engineering, King’s College London, 4th Floor Lambeth Wing, St Thomas’ Hospital, London SE1 7EH, UK

³ Instituto de Química Física Rocasolano (IQFR), Consejo Superior de Investigaciones Científicas (CSIC), Serrano 119, 28006 Madrid, Spain

Molecules 2017, 22(7), 1189; https://doi.org/10.3390/molecules22071189 - 15 Jul 2017

Cited by 4 | Viewed by 6126

Abstract

Linear and cyclic analogues of the α-melanocyte stimulating hormone (α-MSH) targeting the human melanocortin receptor 1 (MC1R) are of pharmacological interest for detecting and treating melanoma. The central sequence of α-MSH (His-Phe-Arg-Trp) has been identified as being essential for receptor binding. To deepen [...] Read more.

Linear and cyclic analogues of the α-melanocyte stimulating hormone (α-MSH) targeting the human melanocortin receptor 1 (MC1R) are of pharmacological interest for detecting and treating melanoma. The central sequence of α-MSH (His-Phe-Arg-Trp) has been identified as being essential for receptor binding. To deepen current knowledge on the molecular basis for α-MSH bioactivity, we aimed to understand the effect of cycle size on receptor binding. To that end, we synthesised two macrocyclic isomeric α-MSH analogues, c[NH-NO₂-C₆H₃-CO-His-DPhe-Arg-Trp-Lys]-Lys-NH₂ (CycN-K6) and c[NH-NO₂-C₆H₃-CO-His-DPhe-Arg-Trp-Lys-Lys]-NH₂ (CycN-K7). Their affinities to MC1R receptor were determined by competitive binding assays, and their structures were analysed by ¹H and ¹³C NMR. These results were compared to those of the previously reported analogue c[S-NO₂-C₆H₃-CO-His-DPhe-Arg-Trp-Cys]-Lys-NH₂ (CycS-C6). The MC1R binding affinity of the 22-membered macrocyclic peptide CycN-K6 (IC₅₀ = 155 ± 16 nM) is higher than that found for the 25-membered macrocyclic analogue CycN-K7 (IC₅₀ = 495 ± 101 nM), which, in turn, is higher than that observed for the 19-membered cyclic analogue CycS-C6 (IC₅₀ = 1770 ± 480 nM). NMR structural study indicated that macrocycle size leads to changes in the relative dispositions of the side chains, particularly in the packing of the Arg side chain relative to the aromatic rings. In contrast to the other analogues, the 22-membered cycle’s side chains are favorably positioned for receptor interaction. Full article

(This article belongs to the Special Issue Peptide-Based Drugs and Drug Delivery Systems)

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Open AccessCommunication

Antiviral Lipopeptide-Cell Membrane Interaction Is Influenced by PEG Linker Length

by Marcelo T. Augusto¹

, Axel Hollmann^1,2,3, Matteo Porotto^4,5, Anne Moscona^4,5,6,7,* and Nuno C. Santos^1,*

¹ Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Av. Prof. Egas Moniz, 1649-028 Lisboa, Portugal

² Laboratory of Molecular Microbiology, Institute of Basic and Applied Microbiology, National University of Quilmes, Roque Sáenz Peña N° 352, Bernal, 1876 Buenos Aires, Argentina

³ Laboratory of Biointerfaces and Biomimetic Systems, CITSE, National University of Santiago del Estero-CONICET, 4200 Santiago del Estero, Argentina

⁴ Center for Host-Pathogen Interaction, Columbia University Medical Center, 701 W. 168th, New York, NY 10032, USA

⁵ Department of Pediatrics, Columbia University Medical Center, 701 W. 168th, New York, NY 10032, USA

⁶ Department of Microbiology & Immunology, Columbia University Medical Center, 701 W. 168th, New York, NY 10032, USA

⁷ Department of Physiology & Cellular Biophysics, Columbia University Medical Center, 701 W. 168th, New York, NY 10032, USA

Molecules 2017, 22(7), 1190; https://doi.org/10.3390/molecules22071190 - 15 Jul 2017

Cited by 12 | Viewed by 5854

Abstract

A set of lipopeptides was recently reported for their broad-spectrum antiviral activity against viruses belonging to the Paramyxoviridae family, including human parainfluenza virus type 3 and Nipah virus. Among them, the peptide with a 24-unit PEG linker connecting it to a cholesterol moiety [...] Read more.

A set of lipopeptides was recently reported for their broad-spectrum antiviral activity against viruses belonging to the Paramyxoviridae family, including human parainfluenza virus type 3 and Nipah virus. Among them, the peptide with a 24-unit PEG linker connecting it to a cholesterol moiety (VG-PEG24-Chol) was found to be the best membrane fusion inhibitory peptide. Here, we evaluated the interaction of the same set of peptides with biomembrane model systems and isolated human peripheral blood mononuclear cells (PBMC). VG-PEG24-Chol showed the highest insertion rate and it was among the peptides that induced a larger change on the surface pressure of cholesterol rich membranes. This peptide also displayed a high affinity towards PBMC membranes. These data provide new information about the dynamics of peptide-membrane interactions of a specific group of antiviral peptides, known for their potential as multipotent paramyxovirus antivirals. Full article

(This article belongs to the Special Issue Peptide-Based Drugs and Drug Delivery Systems)

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Open AccessArticle

Cardamom, Cumin, and Dill Weed Essential Oils: Chemical Compositions, Antimicrobial Activities, and Mechanisms of Action against Campylobacter spp.

by Aysegul Mutlu-Ingok

and Funda Karbancioglu-Guler^*

Department of Food Engineering, Faculty of Chemical and Metallurgical Engineering, Istanbul Technical University, Maslak, 34469 Istanbul, Turkey

Molecules 2017, 22(7), 1191; https://doi.org/10.3390/molecules22071191 - 15 Jul 2017

Cited by 69 | Viewed by 8457

Abstract

Natural antimicrobials as well as essential oils (EOs) have gained interest to inhibit pathogenic microorganisms and to control food borne diseases. Campylobacter spp. are one of the most common causative agents of gastroenteritis. In this study, cardamom, cumin, and dill weed EOs were [...] Read more.

Natural antimicrobials as well as essential oils (EOs) have gained interest to inhibit pathogenic microorganisms and to control food borne diseases. Campylobacter spp. are one of the most common causative agents of gastroenteritis. In this study, cardamom, cumin, and dill weed EOs were evaluated for their antibacterial activities against Campylobacter jejuni and Campylobacter coli by using agar-well diffusion and broth microdilution methods, along with the mechanisms of antimicrobial action. Chemical compositions of EOs were also tested by gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS). The results showed that cardamom and dill weed EOs possess greater antimicrobial activity than cumin with larger inhibition zones and lower minimum inhibitory concentrations. The permeability of cell membrane and cell membrane integrity were evaluated by determining relative electric conductivity and release of cell constituents into supernatant at 260 nm, respectively. Moreover, effect of EOs on the cell membrane of Campylobacter spp. was also investigated by measuring extracellular ATP concentration. Increase of relative electric conductivity, extracellular ATP concentration, and cell constituents’ release after treatment with EOs demonstrated that tested EOs affected the membrane integrity of Campylobacter spp. The results supported high efficiency of cardamom, cumin, and dill weed EOs to inhibit Campylobacter spp. by impairing the bacterial cell membrane. Full article

(This article belongs to the Special Issue Essential Oils as Antimicrobial and Anti-infectious Agents)

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Open AccessReview

Assessment of Enzyme Inhibition: A Review with Examples from the Development of Monoamine Oxidase and Cholinesterase Inhibitory Drugs

by Rona R. Ramsay^1,*,† and Keith F. Tipton^2,†

¹ Biomedical Sciences Research Complex, University of St Andrews, St Andrews KY16 8QP, UK

² School of Biochemistry and Immunology, Trinity College, Dublin 2, Ireland

^† These authors contributed equally to this work.

Molecules 2017, 22(7), 1192; https://doi.org/10.3390/molecules22071192 - 15 Jul 2017

Cited by 161 | Viewed by 24924

Abstract

The actions of many drugs involve enzyme inhibition. This is exemplified by the inhibitors of monoamine oxidases (MAO) and the cholinsterases (ChE) that have been used for several pharmacological purposes. This review describes key principles and approaches for the reliable determination of enzyme [...] Read more.

The actions of many drugs involve enzyme inhibition. This is exemplified by the inhibitors of monoamine oxidases (MAO) and the cholinsterases (ChE) that have been used for several pharmacological purposes. This review describes key principles and approaches for the reliable determination of enzyme activities and inhibition as well as some of the methods that are in current use for such studies with these two enzymes. Their applicability and potential pitfalls arising from their inappropriate use are discussed. Since inhibitor potency is frequently assessed in terms of the quantity necessary to give 50% inhibition (the IC₅₀ value), the relationships between this and the mode of inhibition is also considered, in terms of the misleading information that it may provide. Incorporation of more than one functionality into the same molecule to give a multi-target-directed ligands (MTDLs) requires careful assessment to ensure that the specific target effects are not significantly altered and that the kinetic behavior remains as favourable with the MTDL as it does with the individual components. Such factors will be considered in terms of recently developed MTDLs that combine MAO and ChE inhibitory functions. Full article

(This article belongs to the Special Issue Polypharmacology and Multitarget Drug Discovery)

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Open AccessArticle

Investigation of the Effect of the Degree of Processing of Radix Rehmanniae Preparata (Shu Dihuang) on Shu Dihuangtan Carbonization Preparation Technology

by Xianglong Meng^1,2,†, Meijing He^2,†, Rui Guo², Rui Duan², Fengxian Huo², Chenzi Lv², Bo Wang² and Shuosheng Zhang^2,*

¹ Department of Herbology, College of Korean Medicine, Dongguk University, 38066 Gyeongju, Korea

² Institute of Pharmaceutical & Food Engineering and College of Chinese Materia Medica, Shanxi University of Chinese Medicine, Jinzhong 030619, Shanxi, China

^† These authors contributed equally to this work.

Molecules 2017, 22(7), 1193; https://doi.org/10.3390/molecules22071193 - 18 Jul 2017

Cited by 20 | Viewed by 4637

Abstract

Carbonization of Radix Rehmanniae Preparata (Shu Dihuangtan) via stir-frying could increase its homeostasis maintaining and antidiarrheal effects. To ensure these pharmacological functions, the quality of the raw material (processed Rehmanniae Radix) must be well controlled. Therefore, we analyzed the effects of different degrees [...] Read more.

Carbonization of Radix Rehmanniae Preparata (Shu Dihuangtan) via stir-frying could increase its homeostasis maintaining and antidiarrheal effects. To ensure these pharmacological functions, the quality of the raw material (processed Rehmanniae Radix) must be well controlled. Therefore, we analyzed the effects of different degrees of processing and adjuvants on processed Rehmanniae Radix (Shu Dihuang) by High Performance Liquid Chromatography (HPLC) chromatographic fingerprints, thermal gravimetric analysis and Fourier transform infrared spectroscopy (FTIR). Based on the results from HPLC fingerprints combined with similarity analysis (SA) and hierarchical cluster analysis (HCA) the optimum processing method for Shu Dihuang was five cycles of steaming and polishing, which follows the ancient processing theory. The intensity of thermal weight loss rate peaked near 210.33 ± 4.32 °C or 211.33 ± 2.62 °C, which was an important indicator for the degree of processing of Shu Dihuang. A temperature near 290.89 ± 2.51 °C was the upper limit for carbonizing Shu Dihuangtan. FTIR spectroscopy analysis showed that the overall chemical composition of Shu Dihuangtan was affected by both the degree of processing and adjuvant, which are very important for its quality. Full article

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Open AccessCommunication

Fluorescence Modulation of Green Fluorescent Protein Using Fluorinated Unnatural Amino Acids

by Jordan K. Villa, Hong-Anh Tran, Megha Vipani, Stephanie Gianturco, Konark Bhasin, Brent L. Russell, Elizabeth J. Harbron^* and Douglas D. Young^*

Department of Chemistry, The College of William & Mary, Williamsburg, VA 231871, USA

Molecules 2017, 22(7), 1194; https://doi.org/10.3390/molecules22071194 - 16 Jul 2017

Cited by 13 | Viewed by 8075

Abstract

The ability to modulate protein function through minimal perturbations to amino acid structure represents an ideal mechanism to engineer optimized proteins. Due to the novel spectroscopic properties of green fluorescent protein, it has found widespread application as a reporter protein throughout the fields [...] Read more.

The ability to modulate protein function through minimal perturbations to amino acid structure represents an ideal mechanism to engineer optimized proteins. Due to the novel spectroscopic properties of green fluorescent protein, it has found widespread application as a reporter protein throughout the fields of biology and chemistry. Using site-specific amino acid mutagenesis, we have incorporated various fluorotyrosine residues directly into the fluorophore of the protein, altering the fluorescence and shifting the pKa of the phenolic proton associated with the fluorophore. Relative to wild type GFP, the fluorescence spectrum of the protein is altered with each additional fluorine atom, and the mutant GFPs have the potential to be employed as pH sensors due to the altered electronic properties of the fluorine atoms. Full article

(This article belongs to the Section Bioorganic Chemistry)

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Open AccessCommunication

Anti-Inflammatory Effects of Vitisinol A and Four Other Oligostilbenes from Ampelopsis brevipedunculata var. Hancei

by Chi-I Chang¹, Wei-Chu Chien¹, Kai-Xin Huang¹ and Jue-Liang Hsu^1,2,3,*

¹ Department of Biological Science and Technology, National Pingtung University of Science and Technology, Pingtung 900, Taiwan

² Research Center for Tropic Agriculture, National Pingtung University of Science and Technology, Pingtung 900, Taiwan

³ Research Center for Austronesian Medicine and Agriculture, National Pingtung University of Science and Technology, Pingtung 900, Taiwan

Molecules 2017, 22(7), 1195; https://doi.org/10.3390/molecules22071195 - 17 Jul 2017

Cited by 14 | Viewed by 3803

Abstract

In this study, the cytotoxicities and anti-inflammatory activities of five resveratrol derivatives—vitisinol A, (+)-ε-viniferin, (+)-vitisin A, (−)-vitisin B, and (+)-hopeaphenol—isolated from Ampelopsis brevipedunculata var. hancei were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and lipopolysaccharide (LPS)-stimulated RAW264.7 cells, respectively. The result from MTT assay [...] Read more.

In this study, the cytotoxicities and anti-inflammatory activities of five resveratrol derivatives—vitisinol A, (+)-ε-viniferin, (+)-vitisin A, (−)-vitisin B, and (+)-hopeaphenol—isolated from Ampelopsis brevipedunculata var. hancei were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and lipopolysaccharide (LPS)-stimulated RAW264.7 cells, respectively. The result from MTT assay analysis indicated that vitisinol A has lower cytotoxicity than the other four well-known oligostilbenes. In the presence of vitisinol A (5 μM), the significant reduction of inflammation product (nitric oxide, NO) in LPS-induced RAW264.7 cells was measured using Griess reaction assay. In addition, the under-expressed inflammation factors cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in LPS-induced RAW264.7 cells monitored by Western blotting simultaneously suggested that vitisinol A has higher anti-inflammatory effect compared with other resveratrol derivatives. Finally, the anti-inflammatory effect of vitisinol A was further demonstrated on 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced ear edema in mice. As a preliminary functional evaluation of natural product, the anti-inflammatory effect of vitisinol A is the first to be examined and reported by this study. Full article

(This article belongs to the Section Natural Products Chemistry)

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Open AccessArticle

Larvicidal and Nematicidal Activities of 3-Acylbarbituric Acid Analogues against Asian Tiger Mosquito, Aedes albopictus, and Pine Wood Nematode, Bursaphelenchus xylophilus

by Seon-Mi Seo^1,2, Hyo-Rim Lee^1,2, Ji-Eun Lee¹, Yong-Chul Jeong³, Hyung-Wook Kwon^4,5, Joon-Kwan Moon⁶

, Mark G. Moloney^3,*

and Il-Kwon Park^1,2,*

¹ Department of Forest Sciences, College of Agriculture and Life Sciences, Seoul National University, Seoul 08826, Korea

² Research Institute of Agriculture and Life Science, College of Agriculture and Life Sciences, Seoul National University, Seoul 08826, Korea

³ Chemistry Research Laboratory, University of Oxford, 12 Mansfield Rd, Oxford OS1 3TA, UK

⁴ Division of Life Sciences and Bio-Resource and Environmental Center, College of Life Science & Bioengineering, Incheon National University, 119 Academy-ro, Yeonsu-gu, Incheon 22012, Korea

⁵ Convergence Research Center for Insect Vector, College of Life Science & Bioengineering, Incheon National University, 119 Academy-ro, Yeonsu-gu, Incheon 22012, Korea

⁶ Department of Plant Life and Environmental Sciences, hankyong National University, 327 Jungangro, Anseong, Gyeonggi 17579, Korea

Molecules 2017, 22(7), 1196; https://doi.org/10.3390/molecules22071196 - 17 Jul 2017

Cited by 3 | Viewed by 3906

Abstract

Widespread concern for the occurrence of resistant strains, along with the avoidance of the use of highly toxic insecticides and their wide environmental dispersal, highlights the need for the development of new and safer pest control agents. Natural products provide inspiration for new [...] Read more.

Widespread concern for the occurrence of resistant strains, along with the avoidance of the use of highly toxic insecticides and their wide environmental dispersal, highlights the need for the development of new and safer pest control agents. Natural products provide inspiration for new chemical entities with biological activities, and their analogues are good lead compounds for the development of new pest control agents. For this purpose, we evaluated the larvicidal and nematicidal activities of 48 3-acylbarbituric acid analogues against the Asian tiger mosquito, Aedes albopictus and the pine wood nematode, Bursaphelenchus xylophilus, organisms of increasing global concern. Among the 48 3-acylbarbituric acid analogues, four compounds—10, 14d, 14g and 19b—showed >90% larvicidal activity against Ae. albopictus at 10 μg/mL concentration, and one (compound 10) showed the strongest larvicidal activity against Ae. albopictus, with a LC₅₀ value of 0.22 μg/mL. Only compound 18 showed strong nematicidal activity against pine wood nematode. Most active compounds possessed similar physicochemical properties; thus, actives typically had ClogP values of around 1.40–1.50 and rel-PSA values of 16–17% and these similar cheminformatic characteristics reflect their similar structure. This study indicates that active 3-acylbarbituric acids analogues have potential as lead compounds for developing novel mosquito control agents. Full article

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Open AccessArticle

Synthesis of 2H-Chromenones from Salicylaldehydes and Arylacetonitriles

by Chengcai Li¹, Hailin Zhu^1,2,*, Hang Zhang¹, Yongfeng Yang¹ and Feng Wang^1,2

¹ Zhejiang Provincial Key Laboratory of Fiber Materials and Manufacturing Technology, Zhejiang Sci-Tech University, Xiasha Campous, Hangzhou 310018, China

² Zhejiang Kertice Hi-Tech Fluor-Material Co., LTD, Huzhou 313000, China

Molecules 2017, 22(7), 1197; https://doi.org/10.3390/molecules22071197 - 18 Jul 2017

Cited by 7 | Viewed by 6684

Abstract

An efficient and convenient protocol for the synthesis of 2H-chromenones has been developed. In the presence of ^tBuOK in DMF, good to excellent yields of various chromenones were obtained from the corresponding salicylaldehydes and arylacetonitriles. No protection of inert gas [...] Read more.

An efficient and convenient protocol for the synthesis of 2H-chromenones has been developed. In the presence of ^tBuOK in DMF, good to excellent yields of various chromenones were obtained from the corresponding salicylaldehydes and arylacetonitriles. No protection of inert gas atmosphere is required here. Full article

(This article belongs to the Special Issue Base Metal Catalysis and Green Synthesis)

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Open AccessCommunication

Application of An Improved HPLC-FL Method to Screen Serine Palmitoyl Transferase Inhibitors

by Simone Bertini^1,*

, Giuseppe Saccomanni¹, Sara Del Carlo¹

, Maria Digiacomo¹

, Claudia Gargini¹, Ilaria Piano¹, Giuseppe Matteo Campisi², Riccardo Ghidoni²

, Marco Macchia¹ and Clementina Manera¹

¹ Dipartimento di Farmacia, Università di Pisa, Via Bonanno 6, 56126-Pisa, Italy

² Laboratorio di Biochimica e Biologia Molecolare, Dipartimento di Scienze della Salute, Via A. di Rudinì 8, 20142 Milano, Italy

Molecules 2017, 22(7), 1198; https://doi.org/10.3390/molecules22071198 - 17 Jul 2017

Cited by 1 | Viewed by 3960

Abstract

In this work, we reported the application and validation of an improved high-performance liquid chromatography method coupled with a fluorimetric detector (HPLC-FL) to screen the activity of two heterocyclic derivatives reported as serine palmitoyl transferase (SPT) inhibitors. The analytical conditions were optimized in [...] Read more.

In this work, we reported the application and validation of an improved high-performance liquid chromatography method coupled with a fluorimetric detector (HPLC-FL) to screen the activity of two heterocyclic derivatives reported as serine palmitoyl transferase (SPT) inhibitors. The analytical conditions were optimized in terms of the derivatization procedure, chromatographic condition, extraction procedure, and method validation according to EMEA guidelines. Once fully optimized, the method was applied to assess the SPT-inhibitory activity of the above-mentioned derivatives and of the reference inhibitor myriocin. The obtained results, expressed as a percentage of residual SPT activity, were compared to those obtained with the reference radio immune assay (RIA). The good correlation between the two types of assay demonstrated that the improved HPLC-FL method is suitable for a preliminary and rapid screening of potential SPT-inhibitors. Full article

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Photosynthesis-Inhibiting Activity of 1-[(2-Chlorophenyl)carbamoyl]- and 1-[(2-Nitrophenyl)carbamoyl]naphthalen-2-yl Alkylcarbamates

by Tomas Gonec^1,*

, Josef Stranik¹, Matus Pesko², Jiri Kos³, Michal Oravec⁴, Katarina Kralova⁵ and Josef Jampilek^3,*

¹ Department of Chemical Drugs, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences, Palackeho 1, 61242 Brno, Czech Republic

² Department of Environmental Ecology, Faculty of Natural Sciences, Comenius University, Ilkovicova 6, 84215 Bratislava, Slovakia

³ Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Comenius University, Odbojarov 10, 83232 Bratislava, Slovakia

⁴ Global Change Research Institute CAS, Belidla 986/4a, 60300 Brno, Czech Republic

⁵ Institute of Chemistry, Faculty of Natural Sciences, Comenius University, Ilkovicova 6, 84215 Bratislava, Slovakia

Molecules 2017, 22(7), 1199; https://doi.org/10.3390/molecules22071199 - 17 Jul 2017

Cited by 8 | Viewed by 4150

Abstract

Eight 1-[(2-chlorophenyl)carbamoyl]naphthalen-2-yl alkylcarbamates and eight 1-[(2-nitrophenyl)carbamoyl]naphthalen-2-yl alkylcarbamates were tested for their activity related to the inhibition of photosynthetic electron transport (PET) in spinach (Spinacia oleracea L.) chloroplasts. The PET-inhibiting activity of the compounds was relatively low; the corresponding IC₅₀ values ranged [...] Read more.

Eight 1-[(2-chlorophenyl)carbamoyl]naphthalen-2-yl alkylcarbamates and eight 1-[(2-nitrophenyl)carbamoyl]naphthalen-2-yl alkylcarbamates were tested for their activity related to the inhibition of photosynthetic electron transport (PET) in spinach (Spinacia oleracea L.) chloroplasts. The PET-inhibiting activity of the compounds was relatively low; the corresponding IC₅₀ values ranged from 0.05 to 0.664 mmol/L; and the highest activity within the series of compounds was observed for 1-[(2-chlorophenyl)-carbamoyl]naphthalen-2-yl propylcarbamate. It has been proven that the compounds are PET-inhibitors in photosystem II. Despite rather low PET-inhibiting activities, primary structure-activity trends can be discussed. Full article

(This article belongs to the Special Issue ECSOC-20)

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Serum Albumin Binding and Esterase Activity: Mechanistic Interactions with Organophosphates

by Nikolay V. Goncharov^1,2,*, Daria A. Belinskaia², Vladimir I. Shmurak¹, Maxim A. Terpilowski², Richard O. Jenkins³ and Pavel V. Avdonin⁴

¹ Research Institute of Hygiene, Occupational Pathology and Human Ecology, bld.93 p.o. Kuz’molovsky, Leningrad Region 188663, Russia

² Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, pr. Torez 44, St. Petersburg 194223, Russia

³ School of Allied Health Sciences, De Montfort University, The Gateway, Leicester LE1 9BH, UK

⁴ Koltsov Institute of Developmental Biology, Russian Academy of Sciences, 26 Vavilova str., Moscow 119334, Russia

Molecules 2017, 22(7), 1201; https://doi.org/10.3390/molecules22071201 - 18 Jul 2017

Cited by 64 | Viewed by 10176

Abstract

The albumin molecule, in contrast to many other plasma proteins, is not covered with a carbohydrate moiety and can bind and transport various molecules of endogenous and exogenous origin. The enzymatic activity of albumin, the existence of which many scientists perceive skeptically, is [...] Read more.

The albumin molecule, in contrast to many other plasma proteins, is not covered with a carbohydrate moiety and can bind and transport various molecules of endogenous and exogenous origin. The enzymatic activity of albumin, the existence of which many scientists perceive skeptically, is much less studied. In toxicology, understanding the mechanistic interactions of organophosphates with albumin is a special problem, and its solution could help in the development of new types of antidotes. In the present work, the history of the issue is briefly examined, then our in silico data on the interaction of human serum albumin with soman, as well as comparative in silico data of human and bovine serum albumin activities in relation to paraoxon, are presented. Information is given on the substrate specificity of albumin and we consider the possibility of its affiliation to certain classes in the nomenclature of enzymes. Full article

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Akanthopyrones A–D, α-Pyrones Bearing a 4-O-Methyl-β-d-glucopyranose Moiety from the Spider-Associated Ascomycete Akanthomyces novoguineensis

by Wilawan Kuephadungphan^1,2,†, Soleiman E. Helaly^1,3,†

, Charuwan Daengrot⁴, Souwalak Phongpaichit^2,5, Janet Jennifer Luangsa-ard⁶, Vatcharin Rukachaisirikul^4,7 and Marc Stadler^1,*

¹ Department of Microbial Drugs, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany

² Department of Microbiology, Faculty of Science, Prince of Songkla University, Songkhla 90112, Thailand

³ Department of Chemistry, Faculty of Science, Aswan University, Aswan 81528, Egypt

⁴ Department of Chemistry, Faculty of Science, Prince of Songkla University, Songkhla 90112, Thailand

⁵ Natural Products Research Center of Excellence, Prince of Songkla University, Songkhla 90112, Thailand

⁶ National Centre for Genetic Engineering and Biotechnology (BIOTEC), Pathumthani 12120, Thailand

⁷ Center of Excellence for Innovation in Chemistry, Prince of Songkla University, Songkhla 90112, Thailand

^† These authors contributed equally to this work.

Molecules 2017, 22(7), 1202; https://doi.org/10.3390/molecules22071202 - 18 Jul 2017

Cited by 20 | Viewed by 4579

Abstract

Hypocrealean fungi have proved to be prolific bioactive metabolite producers; they have caught the attention of mycologists throughout the world. However, only a few studies on the insect and spider parasitic genus Akanthomyces have so far been carried out. In this study, we [...] Read more.

Hypocrealean fungi have proved to be prolific bioactive metabolite producers; they have caught the attention of mycologists throughout the world. However, only a few studies on the insect and spider parasitic genus Akanthomyces have so far been carried out. In this study, we report the isolation, structural elucidation and biological activities of four unprecedented glycosylated α-pyrone derivatives, akanthopyrones A–D (1–4), from a culture of Akanthomyces novoguineensis collected in Thailand. The chemical structures of the akanthopyrones were determined by extensive 1D- and 2D-NMR, and HRMS spectroscopic analysis. Their absolute configurations were determined. Akanthopyrone A (1) exhibited weak antimicrobial activity against Bacillus subtilis DSM10 and cytotoxicity against the HeLa cell line KB-3-1, while akanthopyrone D (4) showed weak activity against Candida tenuis MUCL 29892. Full article

(This article belongs to the Section Natural Products Chemistry)

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Open AccessCorrection

Correction: Zielinski, W., et al. Ionic Liquids as Solvents for Rhodium and Platinum Catalysts Used in Hydrosilylation Reaction. Molecules 2016, 21, 1115

by Witold Zielinski¹, Rafal Kukawka^1,2

, Hieronim Maciejewski^1,2 and Marcin Smiglak^1,2,*

¹ Poznan Science and Technology Park, Adam Mickiewicz University Foundation, 46 Rubież ST., 61-612 Poznań, Poland;

² Faculty of Chemistry, Adam Mickiewicz University, Umultowska 89b, 61-614 Poznań,

Molecules 2017, 22(7), 1203; https://doi.org/10.3390/molecules22071203 - 18 Jul 2017

Viewed by 3313

Abstract

The authors are sorry to report that the yield of the hydrosilylation reaction in [P44414][NTf2] (1) IL with [RhCl(PPh3)3] was replaced with the yield reported for [P44414][NTf2] (1) IL with K2PtCl4 in their published paper [1]. [...]
Full article

(This article belongs to the Special Issue Organic Reaction in Green Solvents)

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Open AccessArticle

N-Heterocyclic Carbene Coinage Metal Complexes of the Germanium-Rich Metalloid Clusters [Ge₉R₃]⁻ and [Ge₉R^I₂]²⁻ with R = Si(ⁱPr)₃ and R^I = Si(TMS)₃

by Felix S. Geitner^1,†, Michael A. Giebel^2,†, Alexander Pöthig³ and Thomas F. Fässler^2,*

¹ Wacker Institute for Silicon Chemistry and Department of Chemistry, Technische Universität München, Lichtenbergstraße 4, 85747 Garching, Germany

² Department of Chemistry, Technische Universität München, Lichtenbergstraße 4, 85747 Garching, Germany

³ TUM Catalysis Research Center (CRC), Ernst-Otto-Fischer Straße 1, 85747 Garching, Germany

^† These authors contributed equally to this work.

Molecules 2017, 22(7), 1204; https://doi.org/10.3390/molecules22071204 - 19 Jul 2017

Cited by 26 | Viewed by 5320

Abstract

We report on the synthesis of novel coinage metal NHC (N-heterocyclic carbene) compounds of the germanium-rich metalloid clusters [Ge₉R₃]⁻ and [Ge₉R^I₂]²⁻ with R = Si(ⁱPr)₃ and [...] Read more.

We report on the synthesis of novel coinage metal NHC (N-heterocyclic carbene) compounds of the germanium-rich metalloid clusters [Ge₉R₃]⁻ and [Ge₉R^I₂]²⁻ with R = Si(ⁱPr)₃ and R^I = Si(TMS)₃. NHC^DippCu{η³Ge₉R₃} with R = Si(ⁱPr)₃ (1) represents a less bulky silyl group-substituted derivative of the known analogous compounds with R = Si(ⁱBu)₃ or Si(TMS)₃. The coordination of the [NHC^DippCu]⁺ moiety to the cluster unit occurs via one triangular face of the tri-capped trigonal prismatic [Ge₉] cluster. Furthermore, a series of novel Zintl cluster coinage metal NHC compounds of the type (NHCM)₂{η³Ge₉R^I₂} (R^I = Si(TMS)₃ M = Cu, Ag and Au; NHC = NHC^Dipp or NHC^Mes) is presented. These novel compounds represent a new class of neutral dinuclear Zintl cluster coinage metal NHC compounds, which are obtained either by the stepwise reaction of a suspension of K₁₂Ge₁₇ with Si(TMS)₃Cl and the coinage metal carbene complexes NHCMCl (M = Cu, Ag, Au), or via a homogenous reaction using the preformed bis-silylated cluster K₂[Ge₉(Si(TMS)₃)₂] and the corresponding NHCMCl (M = Cu, Ag, Au) complex. The molecular structures of NHC^DippCu{η³Ge₉(Si(ⁱPr)₃)₃} (1) and (NHC^DippCu)₂{η³-Ge₉(Si(TMS)₃)₂} (2) were determined by single crystal X-ray diffraction methods. In 2, the coordination of the [NHC^DippCu]⁺ moieties to the cluster unit takes place via both open triangular faces of the [Ge₉] entity. Furthermore, all compounds were characterized by means of NMR spectroscopy (¹H, ¹³C, ²⁹Si) and ESI-MS. Full article

(This article belongs to the Special Issue Group 11 Metal Complexes with N-Heterocyclic Carbene Ligands: Recent Developments)

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Preparation of Carriers Based on ZnO Nanoparticles Decorated on Graphene Oxide (GO) Nanosheets for Efficient Immobilization of Lipase from Candida rugosa

by Shan Zhang, Jie Shi^*

, Qianchun Deng, Mingming Zheng, Chuyun Wan, Chang Zheng, Ya Li and Fenghong Huang^*

Hubei Key Laboratory of Lipid Chemistry and Nutrition, Oil Crops and Lipids Process Technology National & Local Joint Engineering Laboratory, Key Laboratory of Oilseeds Processing, Ministry of Agriculture, Oil Crops Research Institute, Chinese Academy of Agricultural Sciences, Wuhan 430062, China

Molecules 2017, 22(7), 1205; https://doi.org/10.3390/molecules22071205 - 19 Jul 2017

Cited by 30 | Viewed by 5748

Abstract

Herein, a promising carrier, graphene oxide (GO) decorated with ZnO nanoparticles, denoted as GO/ZnO composite, has been designed and constructed. This carrier was characterized by X-ray powder diffraction, scanning electron microscopy, Fourier transform infrared spectroscopy and thermogravimetry. Then, Candida rugosa lipase (CRL) was [...] Read more.

Herein, a promising carrier, graphene oxide (GO) decorated with ZnO nanoparticles, denoted as GO/ZnO composite, has been designed and constructed. This carrier was characterized by X-ray powder diffraction, scanning electron microscopy, Fourier transform infrared spectroscopy and thermogravimetry. Then, Candida rugosa lipase (CRL) was immobilized onto the GO-based materials via physical adsorption. Our results indicated that the lipase loading amount on the GO/ZnO composites was about 73.52 mg of protein per g. In the activity assay, the novel immobilized lipase GO/ZnO@CRL, exhibited particularly excellent performance in terms of thermostability and reusability. Within 30 min at 50 °C, the free lipase, GO@CRL and ZnO@CRL had respectively lost 64%, 62% and 41% of their initial activity. However, GO/ZnO@CRL still retained its activity of 63% after 180 min at 50 °C. After reuse of the GO/ZnO@CRL 14 times, 90% of the initial activity can be recovered. Meanwhile, the relative activity of GO@CRL and ZnO@CRL was 28% and 23% under uniform conditions. Hence, GO-decorated ZnO nanoparticles may possess great potential as carriers for immobilizing lipase in a wide range of applications. Full article

(This article belongs to the Special Issue Lipases and Lipases Modification)

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Anti-Inflammatory Triterpene Glycosides from the Roots of Ilex dunniana Levl

by Yu-Sheng Shi^1,2,†, Yan Zhang^3,†, Wen-Zhong Hu¹, Xi Chen^4,5,*, Xin Fu⁶, Xia Lv¹, Li-Hong Zhang³, Ning Zhang³ and Guang Li⁵

¹ Key Laboratory of Biotechnology and Bioresources Utilization, Educational of Minister, College of Life Science, Dalian Nationalities University, Dalian 116600, China

² State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China

³ Jiamusi College, Heilongjiang University of Chinese Medicine, Jiamusi 154007, China

⁴ Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, China

⁵ Yunnan Branch, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Jing Hong 666100, China

⁶ Department of Pharmacognosy, Heilongjiang University of Chinese Medicine, Harbin 150040, China

^† These authors contributed equally to this work.

Molecules 2017, 22(7), 1206; https://doi.org/10.3390/molecules22071206 - 19 Jul 2017

Cited by 7 | Viewed by 3767

Abstract

A new triterpene glycoside ilexdunnoside A (1) and a new sulfated triterpene derivative ilexdunnoside B (2), together with five known analogues 3–7 were isolated from the roots of Ilex dunniana Levl. The structures were established by NMR [...] Read more.

A new triterpene glycoside ilexdunnoside A (1) and a new sulfated triterpene derivative ilexdunnoside B (2), together with five known analogues 3–7 were isolated from the roots of Ilex dunniana Levl. The structures were established by NMR spectroscopic analysis and acid hydrolysis. Results of an in vivo study of the biological activity showed that 75% ethanol and n-butanol extracts of the plant displayed anti-inflammatory activities against ear edema in mice, with inhibition rates of 23.5% and 37.5%, respectively, at a dose of 50 mg/kg. Furthermore, Compounds 1, 2 and 3 exhibited moderate indirect inhibitory effects on lipopolysaccharide-induced NO production in BV2 microglial cells in vitro, with IC₅₀ values of 11.60, 12.30 and 9.70 μM, respectively. Full article

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Structural Insight into the Recognition of r(UAG) by Musashi-1 RBD2, and Construction of a Model of Musashi-1 RBD1-2 Bound to the Minimum Target RNA

by Ryo Iwaoka^1,2

, Takashi Nagata^1,2,*, Kengo Tsuda³, Takao Imai^4,5, Hideyuki Okano⁴, Naohiro Kobayashi⁶ and Masato Katahira^1,2,*

¹ Institute of Advanced Energy, Kyoto University, Gokasho, Uji, Kyoto 611-0011, Japan

² Graduate School of Energy Science, Kyoto University, Gokasho, Uji, Kyoto 611-0011, Japan

³ RIKEN Center for Life Science Technologies, 1-7-22 Suehirocho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan

⁴ Department of Physiology, Keio University School of Medicine, Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan

⁵ Department of Chemistry, Keio University School of Medicine, 4-1-1 Hiyoshi, Kohoku-ku, Yokohama, Kanagawa 223-8521, Japan

⁶ Institute for Protein Research, Osaka University, 3-2 Yamadaoka, Suita, Osaka 565-0871, Japan

Molecules 2017, 22(7), 1207; https://doi.org/10.3390/molecules22071207 - 19 Jul 2017

Cited by 23 | Viewed by 7061

Abstract

Musashi-1 (Msi1) controls the maintenance of stem cells and tumorigenesis through binding to its target mRNAs and subsequent translational regulation. Msi1 has two RNA-binding domains (RBDs), RBD1 and RBD2, which recognize r(GUAG) and r(UAG), respectively. These minimal recognition sequences are connected by variable [...] Read more.

Musashi-1 (Msi1) controls the maintenance of stem cells and tumorigenesis through binding to its target mRNAs and subsequent translational regulation. Msi1 has two RNA-binding domains (RBDs), RBD1 and RBD2, which recognize r(GUAG) and r(UAG), respectively. These minimal recognition sequences are connected by variable linkers in the Msi1 target mRNAs, however, the molecular mechanism by which Msi1 recognizes its targets is not yet understood. We previously determined the solution structure of the Msi1 RBD1:r(GUAGU) complex. Here, we determined the first structure of the RBD2:r(GUAGU) complex. The structure revealed that the central trinucleotide, r(UAG), is specifically recognized by the intermolecular hydrogen-bonding and aromatic stacking interactions. Importantly, the C-terminal region, which is disordered in the free form, took a certain conformation, resembling a helix. The observation of chemical shift perturbation and intermolecular NOEs, together with increases in the heteronuclear steady-state {¹H}-¹⁵N NOE values on complex formation, indicated the involvement of the C-terminal region in RNA binding. On the basis of the two complex structures, we built a structural model of consecutive RBDs with r(UAGGUAG) containing both minimal recognition sequences, which resulted in no steric hindrance. The model suggests recognition of variable lengths (n) of the linker up to n = 50 may be possible. Full article

(This article belongs to the Special Issue Recent Advances in Biomolecular NMR Spectroscopy)

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Isoegomaketone Alleviates the Development of Collagen Antibody-Induced Arthritis in Male Balb/c Mice

by Chang Hyun Jin^1,2

, Yangkang So¹, Bomi Nam¹, Sung Nim Han² and Jin-Baek Kim^1,*

¹ Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup-si, Jeollabuk-do 56212, Korea

² Department of Food and Nutrition, College of Human Ecology, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Korea

Molecules 2017, 22(7), 1209; https://doi.org/10.3390/molecules22071209 - 19 Jul 2017

Cited by 9 | Viewed by 5497

Abstract

In this study, we attempted to identify and assess effects of isoegomaketone (IK) isolated from Perilla frutescens var. crispa on the development of rheumatoid arthritis (RA). RA was induced in male Balb/c mice by collagen antibody injection. Experimental animals were randomly divided into [...] Read more.

In this study, we attempted to identify and assess effects of isoegomaketone (IK) isolated from Perilla frutescens var. crispa on the development of rheumatoid arthritis (RA). RA was induced in male Balb/c mice by collagen antibody injection. Experimental animals were randomly divided into five groups: normal, collagen antibody-induced arthritis (CAIA), CAIA + IK (5 mg/kg/day), CAIA + IK (10 mg/kg/day), and CAIA + apigenin (16 mg/kg/day) and respective treatments were administered via oral gavage once per day for four days. Mice treated with IK (10 mg/kg/day) developed less severe arthritis than the control CAIA mice. Arthritic score, paw volume, and paw thickness were less significant compared to the control CAIA mice at day seven (73%, 15%, and 14% lower, respectively). Furthermore, histopathological examination of ankle for inflammation showed that infiltration of inflammatory cells and edema formation were reduced by IK treatment. Similarly, neutrophil to lymphocyte ratio (NLR) in whole blood was lower in mice treated with IK (10 mg/kg/day) by 85% when compared to CAIA mice. Taken together, treatment with IK delays the onset of the arthritis and alleviates the manifestations of arthritis in CAIA mice. Full article

(This article belongs to the Section Natural Products Chemistry)

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Synthesis, Antitumor Evaluation and Molecular Docking of New Morpholine Based Heterocycles

by Zeinab A. Muhammad¹, Mastoura M. Edrees^1,2

, Rasha A. M. Faty³, Sobhi M. Gomha^3,*

, Seham S. Alterary⁴ and Yahia N. Mabkhot^4,*

¹ Department of Organic Chemistry, National Organization for Drug Control and Research (NODCAR), Giza 12311, Egypt

² Department of Chemistry, Faculty of Science, King Khalid University, Abha 61413, Saudi Arabia

³ Department of Chemistry, Faculty of Science, Cairo University, Giza 12613, Egypt

⁴ Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia

Molecules 2017, 22(7), 1211; https://doi.org/10.3390/molecules22071211 - 20 Jul 2017

Cited by 14 | Viewed by 5839

Abstract

A series of new morpholinylchalcones was prepared and then used as building blocks for constructing a series of 7-morpholino-2-thioxo-2,3-dihydropyrido[2,3-d]pyrimidin-4(1H)-ones via their reaction with 6-aminothiouracil. The latter thiones reacted with the appropriate hydrazonoyl chloride to give the corresponding pyrido[2,3-d [...] Read more.

A series of new morpholinylchalcones was prepared and then used as building blocks for constructing a series of 7-morpholino-2-thioxo-2,3-dihydropyrido[2,3-d]pyrimidin-4(1H)-ones via their reaction with 6-aminothiouracil. The latter thiones reacted with the appropriate hydrazonoyl chloride to give the corresponding pyrido[2,3-d][1,2,4]triazolo[4,3-a]pyrimidin-5(1H)-ones. The assigned structures for all the newly synthesized compounds were confirmed on the basis of elemental analyses and spectral data and the mechanisms of their formation were also discussed. Most of the synthesized compounds were tested for in vitro activity against human lung cancer (A-549) and human hepatocellular carcinoma (HepG-2) cell lines compared with the employed standard antitumor drug (cisplatin) and the results revealed that compounds 8, 4e and 7b have promising activities against the A-549 cell line (IC₅₀ values of 2.78 ± 0.86 μg/mL, 5.37 ± 0.95 μg/mL and 5.70 ± 0.91 μg/mL, respectively) while compound 7b has promising activity against the HepG-2 cell lines (IC₅₀ = 3.54 ± 1.11 μg/mL). Moreover, computational studies using MOE 2014.09 software supported the biological activity results. Full article

(This article belongs to the Collection Heterocyclic Compounds)

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The Anti-Inflammatory Properties of Citrus wilsonii Tanaka Extract in LPS-Induced RAW 264.7 and Primary Mouse Bone Marrow-Derived Dendritic Cells

by Liping Cheng¹, Yujie Ren², Dingbo Lin³, Shu’ang Peng¹, Bo Zhong² and Zhaocheng Ma^1,*

¹ College of Horticulture and Forestry Sciences, Key Laboratory of Horticultural Plant Biology, Huazhong Agricultural University, Ministry of Education, Wuhan 430070, China

² College of Life Sciences, Medical Research Institute, Wuhan University, Wuhan 430072, China

³ Department of Nutritional Sciences, Oklahoma State University, 419 Human Sciences, Stillwater, OK 74078, USA

Molecules 2017, 22(7), 1213; https://doi.org/10.3390/molecules22071213 - 19 Jul 2017

Cited by 43 | Viewed by 8093

Abstract

‘Zhique’ (Citrus wilsonii Tanaka) is a traditional Chinese medicine. Its fruits have been used to treat inflammation-related symptoms, such as cough and sputum, though the underlying mechanism remains poorly understood. The aim of this study was to investigate the anti-inflammatory properties of ‘Zhique’ [...] Read more.

‘Zhique’ (Citrus wilsonii Tanaka) is a traditional Chinese medicine. Its fruits have been used to treat inflammation-related symptoms, such as cough and sputum, though the underlying mechanism remains poorly understood. The aim of this study was to investigate the anti-inflammatory properties of ‘Zhique’ pulp extract (ZQE) in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages and primary mouse bone marrow-derived dendritic cells (BMDCs). The flavonoid profiles of the ZQE were determined by high performance liquid chromatography. The anti-inflammatory activity was evaluated in LPS-induced inflammatory RAW 264.7 macrophages and BMDCs through enzyme-linked immunosorbent assay, quantitative real-time polymerase chain reaction, and Western blot assays. Naringin was a predominant flavonoid occurring in ZQE, followed by eriocitrin, hesperidin, neohesperidin, rhoifolin, naringenin, and poncirin. ZQE exhibited a very low cytotoxicity in LPS-stimulated RAW 264.7 macrophages. Meanwhile, ZQE significantly inhibited the production of prostaglandins E2 and secretion of cyclooxygenase-2 protein in LPS-stimulated RAW 264.7 macrophages, and markedly suppressed the mRNA expression of inflammatory mediators, such as cyclooxygenase-2, tumor necrosis factor alpha, interleukin-1 beta (IL-1β), and IL-6 in LPS-induced RAW 264.7 macrophages and/or primary BMDCs. The ZQE inhibited the inflammatory responses in RAW 264.7 macrophages and BMDCs triggered by LPS. The results suggested that ‘Zhique’ has a high potential as a novel therapeutic agent to treat chronic inflammatory diseases. Full article

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Molecular Weights of Bovine and Porcine Heparin Samples: Comparison of Chromatographic Methods and Results of a Collaborative Survey

by Sabrina Bertini¹

, Giulia Risi^1,2, Marco Guerrini¹, Kevin Carrick³, Anita Y. Szajek^3,4 and Barbara Mulloy^5,*

¹ Istituto di Ricerche Chimiche e Biochimiche “G. Ronzoni” via G. Colombo 81, 20133 Milano, Italy

² Department of Chemistry, University of Pavia, viale Taramelli 12, 27100 Pavia, Italy

³ U.S. Pharmacopeial Convention (USP), 12601 Twinbrook Parkway, Rockville, MD 20852, USA

⁴ Center for Scientific Review (CSR), National Institutes of Health, 6701 Rockledge Dr. Rm. 4187, Bethesda, MD 20892, USA

⁵ Institute of Pharmaceutical Science, Franklin Wilkins Building, King’s College London, 150 Stamford St., London SE1 9NH, UK

Molecules 2017, 22(7), 1214; https://doi.org/10.3390/molecules22071214 - 19 Jul 2017

Cited by 11 | Viewed by 5752

Abstract

In a collaborative study involving six laboratories in the USA, Europe, and India the molecular weight distributions of a panel of heparin sodium samples were determined, in order to compare heparin sodium of bovine intestinal origin with that of bovine lung and porcine [...] Read more.

In a collaborative study involving six laboratories in the USA, Europe, and India the molecular weight distributions of a panel of heparin sodium samples were determined, in order to compare heparin sodium of bovine intestinal origin with that of bovine lung and porcine intestinal origin. Porcine samples met the current criteria as laid out in the USP Heparin Sodium monograph. Bovine lung heparin samples had consistently lower average molecular weights. Bovine intestinal heparin was variable in molecular weight; some samples fell below the USP limits, some fell within these limits and others fell above the upper limits. These data will inform the establishment of pharmacopeial acceptance criteria for heparin sodium derived from bovine intestinal mucosa. The method for MW determination as described in the USP monograph uses a single, broad standard calibrant to characterize the chromatographic profile of heparin sodium on high-resolution silica-based GPC columns. These columns may be short-lived in some laboratories. Using the panel of samples described above, methods based on the use of robust polymer-based columns have been developed. In addition to the use of the USP’s broad standard calibrant for heparin sodium with these columns, a set of conditions have been devised that allow light-scattering detected molecular weight characterization of heparin sodium, giving results that agree well with the monograph method. These findings may facilitate the validation of variant chromatographic methods with some practical advantages over the USP monograph method. Full article

(This article belongs to the Special Issue Looking Forward to the Future of Heparin: New Sources, Developments and Applications)

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Identification of a Novel Vasodilatory Octapeptide from the Skin Secretion of the African Hyperoliid Frog, Kassina senegalensis

by Qiang Du^1,†, Hui Wang^1,*,†, Chengbang Ma², Yue Wu², Xinping Xi^2,*, Mei Zhou²

, Tianbao Chen²

, Chris Shaw² and Lei Wang²

¹ School of Pharmacy, China Medical University, Shenyang 110001, Liaoning, China

² Natural Drug Discovery Group, School of Pharmacy, Queen’s University, Belfast BT9 7BL, Northern Ireland, UK

^† These authors contributed equally to this work.

Molecules 2017, 22(7), 1215; https://doi.org/10.3390/molecules22071215 - 19 Jul 2017

Cited by 3 | Viewed by 4285

Abstract

The defensive skin secretions of amphibians continue to be an excellent source of novel biologically-active peptides. Here we report the identification and pharmacological activity of a novel C-terminally amided myotropic octapeptide from the skin secretion of the African hyperoliid frog, Kassina senegalensis. [...] Read more.

The defensive skin secretions of amphibians continue to be an excellent source of novel biologically-active peptides. Here we report the identification and pharmacological activity of a novel C-terminally amided myotropic octapeptide from the skin secretion of the African hyperoliid frog, Kassina senegalensis. The 8-amino acid peptide has the following primary structure: WMSLGWSL-amide and has a molecular mass of 978 Da. The primary structure and organisation of the biosynthetic precursor of WL-8 amide was successfully deduced from cloned skin secretion-derived cDNA. The open-reading frame encoded a single copy of WL-8, located at the C-terminus. Synthetic WL-8 amide was found to cause relaxation of rat tail artery smooth muscle with an EC₅₀ of 25.98 nM. This peptide is unique in terms of its primary structure and is unlike any other peptide previously isolated from an amphibian source which has been archived in the NCBI database. WL-8 amide thus represents the prototype of a novel family of myotropic peptide from amphibian defensive skin secretions. Full article

(This article belongs to the Special Issue Bioactive Natural Peptides As A Pipeline For Therapeutics)

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Open AccessComment

The Hydrogen Sulfide-Vitamin B12-Folic Acid Axis: An Intriguing Issue in Chronic Kidney Disease. A Comment on Toohey JI: “Possible Involvement of Hydrosulfide in B12-Dependent Methyl Group Transfer”. Molecules 2017, 22, 582, pii: E582

by Giuseppe Cianciolo, Maria Cappuccilli and Gaetano La Manna^*

Department of Experimental, Diagnostic and Specialty Medicine (DIMES)—Nephrology, Dialysis and Transplantation Unit, St. Orsola Hospital, University of Bologna, Via G. Massarenti 9 (Pad. 15), 40138 Bologna, Italy

Molecules 2017, 22(7), 1216; https://doi.org/10.3390/molecules22071216 - 19 Jul 2017

Cited by 3 | Viewed by 4045

Abstract

Dear Editor, We read with great interest the recent article by John I. Toohey entitled “Possible Involvement of Hydrosulfide in B12-Dependent Methyl Group Transfer”, recently published in Molecules 2017, and we wish to discuss some additional insights raised by this important issue into [...] Read more.

Dear Editor, We read with great interest the recent article by John I. Toohey entitled “Possible Involvement of Hydrosulfide in B12-Dependent Methyl Group Transfer”, recently published in Molecules 2017, and we wish to discuss some additional insights raised by this important issue into the nephrological area [1].[...] Full article

(This article belongs to the Special Issue Sulfur Atom: Element for Adaptation to an Oxidative Environment 2016)

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Open AccessReview

Cyclic Peptides as Novel Therapeutic Microbicides: Engineering of Human Defensin Mimetics

by Annarita Falanga^1,†

, Ersilia Nigro^2,3,†

, Margherita Gabriella De Biasi¹, Aurora Daniele^2,3

, Giancarlo Morelli¹, Stefania Galdiero^1,*

and Olga Scudiero^3,4,*

¹ Department of Pharmacy, University of Naples Federico II, via Mezzocannone 16, 80134 Naples, Italy

² Dipartimento di Scienze e Tecnologie Ambientali Biologiche Farmaceutiche, University of Campania “Luigi Vanvitelli”, Via G. Vivaldi 42, 81100 Caserta, Italy

³ CEINGE-Biotecnologie Avanzate Scarl, Via G. Salvatore 486, 80145 Napoli, Italy

⁴ Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli “Federico II”, 80131 Napoli, Italy

^† These two authors contributed equally.

Molecules 2017, 22(7), 1217; https://doi.org/10.3390/molecules22071217 - 20 Jul 2017

Cited by 78 | Viewed by 8585

Abstract

Cyclic peptides are receiving significant attention thanks to their antimicrobial activity and high serum stability, which is useful to develop and design novel antimicrobial agents. Antimicrobial peptides appear to be key components of innate defences against bacteria, viruses, and fungi. Among the others, [...] Read more.

Cyclic peptides are receiving significant attention thanks to their antimicrobial activity and high serum stability, which is useful to develop and design novel antimicrobial agents. Antimicrobial peptides appear to be key components of innate defences against bacteria, viruses, and fungi. Among the others, defensins possess a strong microbicidial activity. Defensins are cationic and amphipathic peptides with six cysteine residues connected by three disulfide bonds found in plants, insects, and mammals; they are divided in three families: α-, β-, and θ-defensins. α-Defensins are contained in the primary granules of human neutrophils; β-defensins are expressed in human epithelia; and θ-defensins are pseudo-cyclic defensins not found in humans, but in rhesus macaques. The structural diversities among the three families are reflected in a different antimicrobial action as well as in serum stability. The engineering of these peptides is an exciting opportunity to obtain more functional antimicrobial molecules highlighting their potential as therapeutic agents. The present review reports the most recent advances in the field of cyclic peptides with a specific regard to defensin analogs. Full article

(This article belongs to the Special Issue Peptide-Based Drugs and Drug Delivery Systems)

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Open AccessArticle

Magnolol, a Natural Polyphenol, Attenuates Dextran Sulfate Sodium-Induced Colitis in Mice

by Ling Zhao¹

, Hai-tao Xiao^1,2, Huai-xue Mu¹, Tao Huang¹, Ze-si Lin^1,3, Linda L. D. Zhong¹, Guang-zhi Zeng⁴, Bao-min Fan⁴, Cheng-yuan Lin^1,4,* and Zhao-xiang Bian^1,2,*

¹ Lab of Brain and Gut Research, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China

² Hong Kong Baptist University Shenzhen Research Institute and Continuing Education, 518057 Shenzhen, China

³ Preparatory Office of Shenzhen-Melbourne Institute of Life Sciences and Bioengineering, Guangzhou University of Chinese Medicine, 510006 Guangzhou, China

⁴ YMU-HKBU Joint Laboratory of Traditional Natural Medicine, Yunnan Minzu University, 650500 Kunming, China

Molecules 2017, 22(7), 1218; https://doi.org/10.3390/molecules22071218 - 20 Jul 2017

Cited by 50 | Viewed by 8731

Abstract

Magnolol is a lignan with anti-inflammatory activity identified in Magnolia officinalis. Ulcerative colitis (UC), one of the types of inflammatory bowel disease (IBD), is a disease that causes inflammation and ulcers in the colon. To investigate the effect of magnolol in dextran [...] Read more.

Magnolol is a lignan with anti-inflammatory activity identified in Magnolia officinalis. Ulcerative colitis (UC), one of the types of inflammatory bowel disease (IBD), is a disease that causes inflammation and ulcers in the colon. To investigate the effect of magnolol in dextran sulfate sodium (DSS)-induced experimental UC model, male C57 mice were treated with 2% DSS drinking water for 5 consecutive days followed by intragastric administration with magnolol (5, 10 and 15 mg/kg) daily for 7 days. The results showed that magnolol significantly attenuated disease activity index, inhibited colonic shortening, reduced colonic lesions and suppressed myeloperoxidase (MPO) activity. Moreover, colonic pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β) induced by colitis were dramatically decreased by magnolol. To further unveil the metabolic signatures upon magnolol treatment, mass spectrometry-based metabolomic analysis of the small molecular metabolites in mice serum were performed. Compared with controls, abnormality of serum metabolic phenotypes in DSS-treated mice were effectively reversed by different doses of magnolol. In particular, magnolol treatment effectively elevated the serum levels of tryptophan metabolites including kynurenic acid (KA), 5-hydroxyindoleacetic acid, indoleacetic acid (IAA), indolelactic acid and indoxylsulfuric acid, which are potential aryl hydrocarbon receptor (AHR) ligands to impact colitis. These findings suggest that magnolol exerts anti-inflammatory effect on DSS-induced colitis and its underlying mechanisms are associated with the restoring of tryptophan metabolites that inhibit the colonic inflammation. Full article

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Fluorination of Naturally Occurring N⁶-Benzyladenosine Remarkably Increased Its Antiviral Activity and Selectivity

by Vladimir E. Oslovsky^1,†

, Mikhail S. Drenichev^1,†

, Liang Sun², Nikolay N. Kurochkin¹, Vladislav E. Kunetsky¹, Carmen Mirabelli², Johan Neyts², Pieter Leyssen² and Sergey N. Mikhailov^1,*

¹ Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, Russia

² Laboratory for Virology and Chemotherapy, Department of Microbiology and Immunology, Rega Institute for Medical Research, KU Leuven-University of Leuven, Minderbroedersstraat 10, Leuven 3000, Belgium

^† The authors contributed equally.

Molecules 2017, 22(7), 1219; https://doi.org/10.3390/molecules22071219 - 20 Jul 2017

Cited by 17 | Viewed by 5060

Abstract

Recently, we demonstrated that the natural cytokinin nucleosides N⁶-isopentenyladenosine (iPR) and N⁶-benzyladenosine (BAPR) exert a potent and selective antiviral effect on the replication of human enterovirus 71. In order to further characterize the antiviral profile [...] Read more.

Recently, we demonstrated that the natural cytokinin nucleosides N⁶-isopentenyladenosine (iPR) and N⁶-benzyladenosine (BAPR) exert a potent and selective antiviral effect on the replication of human enterovirus 71. In order to further characterize the antiviral profile of this class of compounds, we generated a series of fluorinated derivatives of BAPR and evaluated their activity on the replication of human enterovirus 71 in a cytopathic effect (CPE) reduction assay. The monofluorination of the BAPR-phenyl group changed the selectivity index (SI) slightly because of the concomitant high cell toxicity. Interestingly, the incorporation of a second fluorine atom resulted in a dramatic improvement of selectivity. Moreover, N⁶-trifluoromethylbenzyladenosine derivatives (9–11) exhibited also a very interesting profile, with low cytotoxicity observed. In particular, the analogue N⁶-(3-trifluoromethylbenzyl)-adenosine (10) with a four-fold gain in potency as compared to BAPR and the best SI in the class represents a promising candidate for further development. Full article

(This article belongs to the Special Issue Nucleoside and Nucleotide Analogues)

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Special Issue: Adenosine Receptors

by Francisco Ciruela^1,2,* and Eddy Sotelo^3,4

¹ Unitat de Farmacologia, Departament Patologia i Terapèutica Experimental, Facultat de Medicina, IDIBELL-Universitat de Barcelona, L’Hospitalet de Llobregat, 08907 Barcelona, Spain

² Institut de Neurociències, Universitat de Barcelona, 08035 Barcelona, Spain

³ Centro Singular de Investigación en Química Biolóxica e Materiais Moleculares (CIQUS), Universidad de Santiago de Compostela, 15782 Santiago de Compostela, Spain

⁴ Departamento de Química Orgánica, Facultad de Farmacia, Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain

Molecules 2017, 22(7), 1220; https://doi.org/10.3390/molecules22071220 - 20 Jul 2017

Cited by 4 | Viewed by 3475

Abstract

Nearly 90 years ago, Drury and Szent-Györgyi revealed that adenosine produced profound hypotension and bradycardia, and it affected kidney function in mammals [1]. [...]
Full article

(This article belongs to the Special Issue Adenosine Receptors)

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Characterization of Essential Oil Composition in Different Basil Species and Pot Cultures by a GC-MS Method

by Andrea Muráriková¹, Anton Ťažký^2,3, Jarmila Neugebauerová¹, Alexandra Planková², Josef Jampílek⁴

, Pavel Mučaji⁵ and Peter Mikuš^2,3,*

¹ Department of Vegetable Growing and Floriculture, Faculty of Horticulture, Mendel University in Brno, Valtická 337, 691 44 Lednice, Czech Republic

² Department of Pharmaceutical Analysis and Nuclear Pharmacy, Faculty of Pharmacy, Comenius University in Bratislava, Odbojárov 10, SK-832 32 Bratislava, Slovak Republic

³ Toxicological and Antidoping center, Faculty of Pharmacy, Comenius University in Bratislava, Odbojárov 10, SK-832 32 Bratislava, Slovak Republic

⁴ Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Comenius University in Bratislava, Odbojárov 10, SK-832 32 Bratislava, Slovak Republic

⁵ Department of Pharmacognosy and Botany, Faculty of Pharmacy, Comenius University in Bratislava, Odbojárov 10, SK-832 32 Bratislava, Slovak Republic

Molecules 2017, 22(7), 1221; https://doi.org/10.3390/molecules22071221 - 20 Jul 2017

Cited by 58 | Viewed by 8499

Abstract

Basil (Ocimum L.) species are used as medicinal plants due to their essential oils exhibiting specific biological activity. The present work demonstrated that both the variety and season/conditions of cultivation had a significant effect on (i) the produced amount (extraction yield), (ii) [...] Read more.

Basil (Ocimum L.) species are used as medicinal plants due to their essential oils exhibiting specific biological activity. The present work demonstrated that both the variety and season/conditions of cultivation had a significant effect on (i) the produced amount (extraction yield), (ii) qualitative, as well as (iii) quantitative profile of basil essential oil. Among studied basil varieties, a new variety, ‘Mánes’, was characterized for the first time. Based on our quantitative evaluation of GC-MS profiles, the following chemotypes and average concentrations of a main component were detected in the studied basil varieties: ‘Ohře’, ‘Lettuce Leaf’, ‘Purple Opaal’, ‘Dark Green’ (linalool, 5.99, 2.49, 2.34, 2.01 mg/mL, respectively), and ‘Mammolo Genovese’, ‘Mánes’, ‘Red Rubin’ (eucalyptol, 1.34, 0.96, 0.76 mg/mL, respectively). At the same time, when considering other compounds identified in GC-MS profiles, all the studied varieties, except from ‘Lettuce Leaf’, were methyl eugenol-rich with a strong dependence of the eugenol:methyl eugenol ratio on the seasonal changes (mainly solar irradiation, but also temperature and relative humidity). More complex and/or variable (depending on the season and cultivation) chemotypes were observed with ‘Lettuce Leaf’ (plus estragole, 2.27 mg/mL), ‘Dark Green’ (plus eucalyptol, 1.36 mg/mL), ‘Mammolo Genovese’ (plus eugenol, 1.19 mg/mL), ‘Red Rubin’ (plus linalool and eugenol, 0.46 and 0.56 mg/mL, respectively), and ‘Mánes’ (plus linalool and eugenol, 0.58 and 0.40 mg/mL, respectively). When considering superior extraction yield (ca. 17 mL·kg⁻¹, i.e., two to five times higher than other examined varieties) and consistent amounts (yields) of essential oil when comparing inter-seasonal or inter-year data (RSD and inter-year difference in mean yield values ˂2.5%), this new basil variety is very promising for use in the pharmaceutical, food, and cosmetic industries. Full article

(This article belongs to the Section Natural Products Chemistry)

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Open AccessArticle

Application of Ammonium Persulfate for Selective Oxidation of Guanines for Nucleic Acid Sequencing

by Yafen Wang^1,2,†

, Chaoxing Liu^1,2,†, Tingting Hong^1,2, Fan Wu^1,2, Shuyi Yu^1,2, Zhiyong He^1,2, Wuxiang Mao³ and Xiang Zhou^1,2,*

¹ Key Laboratory of Biomedical Polymers of Ministry of Education, College of Chemistry and Molecular Sciences, Wuhan University, Wuhan 430072, Hubei, China

² The Institute for Advanced Studies, Wuhan University, Wuhan 430072, Hubei, China

³ Hubei Collaborative Innovation Center for Green Transformation of Bio-Resources, College of Life Sciences, Hubei University, Wuhan 430062, Hubei, China

^† These authors contributed equally to this work and should be considered as co-first authors.

Molecules 2017, 22(7), 1222; https://doi.org/10.3390/molecules22071222 - 21 Jul 2017

Cited by 2 | Viewed by 6416

Abstract

Nucleic acids can be sequenced by a chemical procedure that partially damages the nucleotide positions at their base repetition. Many methods have been reported for the selective recognition of guanine. The accurate identification of guanine in both single and double regions of DNA [...] Read more.

Nucleic acids can be sequenced by a chemical procedure that partially damages the nucleotide positions at their base repetition. Many methods have been reported for the selective recognition of guanine. The accurate identification of guanine in both single and double regions of DNA and RNA remains a challenging task. Herein, we present a new, non-toxic and simple method for the selective recognition of guanine in both DNA and RNA sequences via ammonium persulfate modification. This strategy can be further successfully applied to the detection of 5-methylcytosine by using PCR. Full article

(This article belongs to the Special Issue Nucleic Acid Chemistry and Nucleic Acid Drugs: A Themed Issue in Honor of Professor Lihe Zhang on the Occasion of His 80th Birthday)

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Open AccessArticle

Neighbor Affinity-Based Core-Attachment Method to Detect Protein Complexes in Dynamic PPI Networks

by Xiujuan Lei^* and Jing Liang

School of Computer Science, Shaanxi Normal University, Xi’an 710119, China

Molecules 2017, 22(7), 1223; https://doi.org/10.3390/molecules22071223 - 24 Jul 2017

Cited by 7 | Viewed by 5617

Abstract

Protein complexes play significant roles in cellular processes. Identifying protein complexes from protein-protein interaction (PPI) networks is an effective strategy to understand biological processes and cellular functions. A number of methods have recently been proposed to detect protein complexes. However, most of methods [...] Read more.

Protein complexes play significant roles in cellular processes. Identifying protein complexes from protein-protein interaction (PPI) networks is an effective strategy to understand biological processes and cellular functions. A number of methods have recently been proposed to detect protein complexes. However, most of methods predict protein complexes from static PPI networks, and usually overlook the inherent dynamics and topological properties of protein complexes. In this paper, we proposed a novel method, called NABCAM (Neighbor Affinity-Based Core-Attachment Method), to identify protein complexes from dynamic PPI networks. Firstly, the centrality score of every protein is calculated. The proteins with the highest centrality scores are regarded as the seed proteins. Secondly, the seed proteins are expanded to complex cores by calculating the similarity values between the seed proteins and their neighboring proteins. Thirdly, the attachments are appended to their corresponding protein complex cores by comparing the affinity among neighbors inside the core, against that outside the core. Finally, filtering processes are carried out to obtain the final clustering result. The result in the DIP database shows that the NABCAM algorithm can predict protein complexes effectively in comparison with other state-of-the-art methods. Moreover, many protein complexes predicted by our method are biologically significant. Full article

(This article belongs to the Special Issue Computational Analysis for Protein Structure and Interaction)

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Effects of Chlorhexidine-Encapsulated Mesoporous Silica Nanoparticles on the Anti-Biofilm and Mechanical Properties of Glass Ionomer Cement

by Huiyi Yan^†, Hongye Yang^†, Kang Li, Jian Yu and Cui Huang^*

¹ The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory for Oral Biomedical Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan 430079, China

^† These two authors contributed equally to this work.

Molecules 2017, 22(7), 1225; https://doi.org/10.3390/molecules22071225 - 21 Jul 2017

Cited by 39 | Viewed by 7287

Abstract

One of the primary causes for the failure of glass ionomer cement (GIC) is secondary caries. To enhance the anti-microbial performance of GIC without affecting its mechanical properties, chlorhexidine (CHX) was encapsulated in expanded-pore mesoporous silica nanoparticles (pMSN) to synthesize CHX@pMSN. CHX@pMSN was [...] Read more.

One of the primary causes for the failure of glass ionomer cement (GIC) is secondary caries. To enhance the anti-microbial performance of GIC without affecting its mechanical properties, chlorhexidine (CHX) was encapsulated in expanded-pore mesoporous silica nanoparticles (pMSN) to synthesize CHX@pMSN. CHX@pMSN was added at three mass fractions (1%, 5%, and 10% (w/w)) to GIC powder as the experimental groups. Pure GIC was set as the control group. The mechanical and anti-biofilm properties of GIC from each group were tested. The results demonstrated that CHX was successfully encapsulated on/into pMSN, and the encapsulating efficiency of CHX was 44.62% in CHX@pMSN. The anti-biofilm ability was significantly enhanced in all experimental groups (p < 0.001) compared with that in the control group. CHX was continuously released, and anti-biofilm ability was maintained up to 30 days. In addition, the mechanical properties (compressive strength, surface hardness, elastic modulus, water sorption, and solubility) of 1% (w/w) group were maintained compared with those in the control group (p > 0.05). In conclusion, adding 1% (w/w) CHX@pMSN to GIC led to conspicuous anti-biofilm ability and had no adverse effect on the mechanical properties of this restorative material. This study proposes a new strategy for preventing secondary caries by using CHX@pMSN-modified GIC. Full article

(This article belongs to the Special Issue Mesoporous Silica in Biomedical Applications)

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Study on Chemical Profile and Neuroprotective Activity of Myrica rubra Leaf Extract

by Pinghong Chen^1,2,†, Xianzong Lin^1,†, Ching-Hsu Yang^3,†, Xu Tang², Yu-Wei Chang⁴, Weibing Zheng⁵, Lianzhong Luo^1,6, Changan Xu^2,* and Yung-Husan Chen^1,6,7,*

¹ Department of Pharmacy, Xiamen Medical College, Xiamen 361023, China

² Engineering Research Center of Marine Biological Resource Comprehensive Utilization, Third Institute of Oceanography, State Oceanic Administration, Xiamen 361005, China

³ Fineboon Dairy Nutrition Institute, Shaanxi Dairy Co. Ltd., Xianyang 712000, China

⁴ Department of Food Science, National Taiwan Ocean University, Keelung 202, Taiwan

⁵ Key Laboratory of Marine Biogenetic Resources, Third Institute of Oceanography, State Oceanic Administration, Xiamen 361005, China

⁶ Xiamen Key Laboratory of Marine Medicinal Natural Products and Cell Engineering, Xiamen Medical College, Xiamen 361008, China

⁷ Key Laboratory for Dao-Di Herbs Biotechnology of Fujian Province, Xiamen Medical College, Xiamen 361023, China

^† These authors contributed equally to this work.

Molecules 2017, 22(7), 1226; https://doi.org/10.3390/molecules22071226 - 24 Jul 2017

Cited by 11 | Viewed by 5237

Abstract

The chemical profile of Myrica rubra (a native species in China) leaf extract was investigated by UPLC-PDA-HRMS, and the neuroprotective activity of two characteristic constituents, myricanol and myricetrin, was evaluated with N2a cells using H₂O₂-inducedoxidative challenge through a series [...] Read more.

The chemical profile of Myrica rubra (a native species in China) leaf extract was investigated by UPLC-PDA-HRMS, and the neuroprotective activity of two characteristic constituents, myricanol and myricetrin, was evaluated with N2a cells using H₂O₂-inducedoxidative challenge through a series of methods, e.g., MTT assay, ROS assay and [Ca²⁺]i assay. Among the 188 constituents detected in the extract of Myrica rubra leaf, 116 were identified definitely or tentatively by the comprehensive utilization of precise molecular weight and abundant multistage fragmentation information obtained by quadrupole orbitrap mass spectrometry. In addition, 14 potential new compounds were reported for the first time. This work established an example for the research of microconstituents in a complex analyte and revealed that suppression of H₂O₂-induced cytotoxicity in N2a cells was achieved by the pretreatment with myricanol. The evidence suggested myricanol may potentially serve as a remedy for prevention and therapy of neurodegenerative diseases induced by oxidative stress. Full article

(This article belongs to the Section Natural Products Chemistry)

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Characterization and Purification of Bergamottin from Citrus grandis (L.) Osbeck cv. Yongjiazaoxiangyou and Its Antiproliferative Activity and Effect on Glucose Consumption in HepG2 cells

by Yilong Liu¹, Chuanhong Ren¹, Yunlin Cao¹, Yue Wang¹, Wenyi Duan¹, Linfeng Xie¹, Chongde Sun¹ and Xian Li^1,2,*

¹ Zhejiang Provincial Key Laboratory of Horticultural Plant Integrative Biology, Zhejiang University, Zijingang Campus, Hangzhou 310058, China

² Laboratory of Fruit Quality Biology, Zhejiang University, Zijingang Campus, Hangzhou 310058, China

Molecules 2017, 22(7), 1227; https://doi.org/10.3390/molecules22071227 - 20 Jul 2017

Cited by 32 | Viewed by 5635

Abstract

Bergamottin is a natural furanocoumarin compound with weak polarity. Characterization and quantification of bergamottin were carried out in different fruit tissues of various citrus cultivars. Among the four citrus tissues tested, i.e., flavedo, albedo, segment membrane (SM), and juice sacs (JS) in eight [...] Read more.

Bergamottin is a natural furanocoumarin compound with weak polarity. Characterization and quantification of bergamottin were carried out in different fruit tissues of various citrus cultivars. Among the four citrus tissues tested, i.e., flavedo, albedo, segment membrane (SM), and juice sacs (JS) in eight citrus cultivars, the highest bergamottin content was found in the flavedo of Citrus grandis (L.) Osbeck cv. Yongjiazaoxiangyou (YJZXY, 666.54 μg·g⁻¹ DW). A combination of silica gel column chromatography and high-speed counter-current chromatography (HSCCC) was established to efficiently purify bergamottin from the flavedo of YJZXY. Bergamottin showed significant antiproliferative activity on three cancer cell lines, i.e., human liver cancer HepG2, promyelocytic leukemia HL-60, and gastric cancer BGC-823 cells, which showed a marked inhibition effect on these cell lines in a dose-dependent manner. In addition, bergamottin significantly increased glucose consumption in HepG2 cells also in a dose-dependent manner, which is the first report of its potential in anti-diabetes applications. Full article

(This article belongs to the Section Natural Products Chemistry)

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High-Resolution Inhibition Profiling Combined with HPLC-HRMS-SPE-NMR for Identification of PTP1B Inhibitors from Vietnamese Plants

by Binh Thi Dieu Trinh, Anna K. Jäger^* and Dan Staerk

Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark

Molecules 2017, 22(7), 1228; https://doi.org/10.3390/molecules22071228 - 20 Jul 2017

Cited by 12 | Viewed by 6092

Abstract

Protein tyrosine phosphatase 1B (PTP1B) plays a key role as a negative regulator in insulin signal transduction by deactivating the insulin receptor. Thus, PTP1B inhibition has emerged as a potential therapeutic strategy for curing insulin resistance. In this study, 40 extracts from 18 [...] Read more.

Protein tyrosine phosphatase 1B (PTP1B) plays a key role as a negative regulator in insulin signal transduction by deactivating the insulin receptor. Thus, PTP1B inhibition has emerged as a potential therapeutic strategy for curing insulin resistance. In this study, 40 extracts from 18 different plant species were investigated for PTP1B inhibitory activity in vitro. The most promising one, the EtOAc extract of Ficus racemosa, was investigated by high-resolution PTP1B inhibition profiling combined with HPLC-HRMS-SPE-NMR analysis. This led to the identification of isoderrone (1), derrone (2), alpinumisoflavone (3) and mucusisoflavone B (4) as PTP1B inhibitors. IC₅₀ of these compounds were 22.7 ± 1.7, 12.6 ± 1.6, 21.2 ± 3.8 and 2.5 ± 0.2 µM, respectively. Kinetics analysis revealed that these compounds inhibited PTP1B non-competitively with K_i values of 21.3 ± 2.8, 7.9 ± 1.9, 14.3 ± 2.0, and 3.0 ± 0.5 µM, respectively. These findings support the important role of F. racemosa as a novel source of new drugs and/or as a herbal remedy for treatment of type 2 diabetes. Full article

(This article belongs to the Special Issue Bioactive Compounds for Metabolic Syndrome and Type 2 Diabetes)

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Effects of K11R and G31P Mutations on the Structure and Biological Activities of CXCL8: Solution Structure of Human CXCL8_(3-72)K11R/G31P

by Hsi-Tsung Cheng¹, Hui-Yuan Yu¹, John R. Gordon²

, Fang Li^3,* and Jya-Wei Cheng^1,*

¹ Institute of Biotechnology and Department of Medical Science, National Tsing Hua University, Hsinchu 300, Taiwan

² Division of Respirology, Critical Care and Sleep Medicine, Department of Medicine, University of Saskatchewan, Saskatoon, SK S7N 5B4, Canada

³ Department of Immunology, Dalian Medical University, Dalian 116044, China

Molecules 2017, 22(7), 1229; https://doi.org/10.3390/molecules22071229 - 21 Jul 2017

Cited by 5 | Viewed by 5186

Abstract

The ELR-CXC chemokines are important to neutrophil inflammation in many acute and chronic diseases. Among them, CXCL8 (interleukin-8, IL-8), the expression levels of which are elevated in many inflammatory diseases, binds to both the CXCR1 and CXCR2 receptors with high affinity. Recently, an [...] Read more.

The ELR-CXC chemokines are important to neutrophil inflammation in many acute and chronic diseases. Among them, CXCL8 (interleukin-8, IL-8), the expression levels of which are elevated in many inflammatory diseases, binds to both the CXCR1 and CXCR2 receptors with high affinity. Recently, an analogue of human CXCL8, CXCL8_(3–72)K11R/G31P (hG31P) has been developed. It has been demonstrated that hG31P is a high affinity antagonist for both the CXCR1 and CXCR2. Herein, we have determined the solution structure and the CXCR1 N-terminal peptide binding sites of hG31P by NMR spectroscopy. We have found that the displacement within the tertiary structure of the 30 s loop and the N-terminal region and more specifically change of the loop conformation (especially H33), of hG31P may affect its binding to the CXCR1 receptor and thereby inhibit human neutrophil chemotactic responses induced by ELR-CXC chemokines. Our results provide a structural basis for future clinical investigations of this CXCR1/CXCR2 receptor antagonist and for the further development of CXCL8 based antagonists. Full article

(This article belongs to the Special Issue Recent Advances in Biomolecular NMR Spectroscopy)

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The Influence of Glycosylation of Natural and Synthetic Prenylated Flavonoids on Binding to Human Serum Albumin and Inhibition of Cyclooxygenases COX-1 and COX-2

by Tomasz Tronina^1,*

, Paulina Strugała², Jarosław Popłoński¹, Aleksandra Włoch², Sandra Sordon¹, Agnieszka Bartmańska¹ and Ewa Huszcza¹

¹ Department of Chemistry, Wrocław University of Environmental and Life Sciences, Norwida 25, 50-375 Wrocław, Poland

² Department of Physics and Biophysics, Wrocław University of Environmental and Life Sciences, Norwida 25, 50-375 Wrocław, Poland

Molecules 2017, 22(7), 1230; https://doi.org/10.3390/molecules22071230 - 21 Jul 2017

Cited by 37 | Viewed by 6772

Abstract

The synthesis of different classes of prenylated aglycones (α,β-dihydroxanthohumol (2) and (Z)-6,4’-dihydroxy-4-methoxy-7-prenylaurone (3)) was performed in one step reactions from xanthohumol (1)—major prenylated chalcone naturally occurring in hops. Obtained flavonoids (2–3) [...] Read more.

The synthesis of different classes of prenylated aglycones (α,β-dihydroxanthohumol (2) and (Z)-6,4’-dihydroxy-4-methoxy-7-prenylaurone (3)) was performed in one step reactions from xanthohumol (1)—major prenylated chalcone naturally occurring in hops. Obtained flavonoids (2–3) and xanthohumol (1) were used as substrates for regioselective fungal glycosylation catalyzed by two Absidia species and Beauveria bassiana. As a result six glycosides (4–9) were formed, of which four glycosides (6–9) have not been published so far. The influence of flavonoid skeleton and the presence of glucopyranose and 4-O-methylglucopyranose moiety in flavonoid molecule on binding to main protein in plasma, human serum albumin (HSA), and inhibition of cyclooxygenases COX-1 and COX-2 were investigated. Results showed that chalcone (1) had the highest binding affinity to HSA (8.624 × 10⁴ M⁻¹) of all tested compounds. It has also exhibited the highest inhibition of cyclooxygenases activity, and it was a two-fold stronger inhibitor than α,β-dihydrochalcone (2) and aurone (3). The presence of sugar moiety in flavonoid molecule caused the loss of HSA binding activity as well as the decrease in inhibition of cyclooxygenases activity. Full article

(This article belongs to the Special Issue Synthesis and Biological Applications of Glycoconjugates)

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3739 KiB

Open AccessArticle

Spectrum Effect Relationship and Component Knock-Out in Angelica Dahurica Radix by High Performance Liquid Chromatography-Q Exactive Hybrid Quadrupole-Orbitrap Mass Spectrometer

by Jinmei Wang^1,2,†, Linna Peng^1,†, Mengjun Shi¹, Changqin Li¹, Yan Zhang^3,† and Wenyi Kang^1,2,*

¹ Institute of Chinese Materia Medica, Henan University, Kaifeng 475004, China

² Kaifeng Key Laboratory of Functional Components in Health Food, Henan University, Kaifeng, Henan 475004, China

³ Hebei Food Inspection and Research Institute, Shijiazhuang 050091, China

^† These authors contributed equally to this work.

Molecules 2017, 22(7), 1231; https://doi.org/10.3390/molecules22071231 - 21 Jul 2017

Cited by 26 | Viewed by 6788

Abstract

Different extracts of Angelica dahuricae were available for whitening or treating vitiligo clinically. They showed inhibitory or activating effects on tyrosinase, a rate-limiting enzyme of melanogenesis. This study aimed to identify active compounds on tyrosinase in water extract of Angelica dahurica Radix. We [...] Read more.

Different extracts of Angelica dahuricae were available for whitening or treating vitiligo clinically. They showed inhibitory or activating effects on tyrosinase, a rate-limiting enzyme of melanogenesis. This study aimed to identify active compounds on tyrosinase in water extract of Angelica dahurica Radix. We applied spectrum-effect relationship and component knock-out methods to make it clear. HPLC was used to obtain the specific chromatograms. The effects on tyrosinase activity were examined by measuring the oxidation rate of levodopa in vitro. Partial least squares method was used to examine the spectrum-effect relationships. The knocked-out samples were prepared by HPLC method, and the identification of knocked-out compounds was conducted by the high performance liquid chromatography-four stage rod-electrostatic field orbit trap high resolution mass spectrometry. Results showed that S6, S14, S18, S21, S35, S36, S37, S40, and S41 were positively correlated to inhibitory activity of Angelica dahuricae on tyrosinase whereas S9, S11, S8, S12, S22, and S30 were negatively correlated. When the concentration of each sample was 1 g·mL⁻¹, equal to the amount of raw medicinal herbs, oxypeucedanin hydrate, imperatorin, cnidilin, and isoimperatorin had inhibitory effects on tyrosinase activity whereas byakangelicin and bergapten had activating effects. Full article

(This article belongs to the Collection Herbal Medicine Research)

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Open AccessArticle

Synthesis and Biological Evaluation of Ginsenoside Compound K Derivatives as a Novel Class of LXRα Activator

by Yan Huang^1,†, Hongmei Liu^1,†, Yingxian Zhang¹, Jin Li¹, Chenping Wang¹, Li Zhou², Yi Jia^1,* and Xiaohui Li^1,*

¹ Institute of Materia Medica and Department of Pharmaceutics, College of Pharmacy, Third Military Medical University, Shapingba, Chongqing 400038, China

² Department of Pharmacy, Xinqiao Hospital & The Second Affiliated Hospital, Third Military Medical University, Shapingba, Chongqing 400037, China

^† These authors contributed equally to this work.

Molecules 2017, 22(7), 1232; https://doi.org/10.3390/molecules22071232 - 24 Jul 2017

Cited by 24 | Viewed by 4641

Abstract

Compound K is one of the active metabolites of Panaxnotoginseng saponins, which could attenuate the formation of atherosclerosis in mice modelsvia activating LXRα. We synthesized and evaluated a series of ginsenoside compound K derivatives modified with short chain fatty acids. All of the [...] Read more.

Compound K is one of the active metabolites of Panaxnotoginseng saponins, which could attenuate the formation of atherosclerosis in mice modelsvia activating LXRα. We synthesized and evaluated a series of ginsenoside compound K derivatives modified with short chain fatty acids. All of the structures of this class of ginsenoside compound K derivative exhibited comparable or better biological activity than ginsenoside compound K. Especially structure 1 exhibited the best potency (cholesteryl ester content: 41.51%; expression of ABCA1 mRNA: 319%) and low cytotoxicity. Full article

(This article belongs to the Section Medicinal Chemistry)

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6857 KiB

Open AccessArticle

Synthesis, Physico-chemical Characterization, Crystal Structure and Influence on Microbial and Tumor Cells of Some Co(II) Complexes with 5,7-Dimethyl-1,2,4-triazolo[1,5-a]pyrimidine

by Luminiţa Măruţescu^1,2, Larisa Calu³

, Mariana Carmen Chifiriuc^1,2, Coralia Bleotu⁴, Constantin-Gabriel Daniliuc⁵, Denisa Fălcescu³

, Crina Maria Kamerzan^1,2

, Mihaela Badea^3,* and Rodica Olar^3,*

¹ Department of Microbiology, Faculty of Biology, University of Bucharest, 1–3 Aleea Portocalelor Str., 60101 Bucharest, Romania

² Environment and Earth Sciences Department, Research Institute of the University of Bucharest—ICUB, Life, Spl. Independentei 91–95, 010271 Bucharest, Romania

³ Department of Inorganic Chemistry, Faculty of Chemistry, University of Bucharest, 90–92 Panduri Str., 050663 Bucharest, Romania

⁴ Stefan S Nicolau Institute of Virology, 285 Mihai Bravu Ave., 030304 Bucharest, Romania

⁵ Organisch-Chemisches Institut, Westfälische Wilhelms-Universität Münster, Corrensstrasse 40, 48149 Münster, Germany

Molecules 2017, 22(7), 1233; https://doi.org/10.3390/molecules22071233 - 22 Jul 2017

Cited by 9 | Viewed by 5327

Abstract

Three complexes, namely [Co(dmtp)₂(OH₂)₄][CoCl₄] (1), [Co(dmtp)₂Cl₂] (2) and [Co(dmtp)₂(OH₂)₄]Cl₂∙2H₂O (3) (dmtp: 5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidine), were [...] Read more.

Three complexes, namely [Co(dmtp)₂(OH₂)₄][CoCl₄] (1), [Co(dmtp)₂Cl₂] (2) and [Co(dmtp)₂(OH₂)₄]Cl₂∙2H₂O (3) (dmtp: 5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidine), were synthesized and characterized by spectral (IR, UV-Vis-NIR), and magnetic measurements at room temperature, as well as single crystal X-ray diffraction. Complex (1) crystallizes in monoclinic system (space group C2/c), complex (2) adopts an orthorhombic system (space group Pbca), and complex (3) crystallizes in triclinic system (space group P1). Various types of extended hydrogen bonds and π–π interactions provide a supramolecular architecture for all complexes. All species were evaluated for antimicrobial activity towards planktonic and biofilm-embedded microbial cells and influence on HEp-2 cell viability, cellular cycle and gene expression. Full article

(This article belongs to the Section Organometallic Chemistry)

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1522 KiB

Open AccessArticle

New Cinchona Oximes Evaluated as Reactivators of Acetylcholinesterase and Butyrylcholinesterase Inhibited by Organophosphorus Compounds

by Maja Katalinić¹, Antonio Zandona¹, Alma Ramić², Tamara Zorbaz¹, Ines Primožič^2,* and Zrinka Kovarik^1,*

¹ Institute for Medical Research and Occupational Health, POB 291, HR-10001 Zagreb, Croatia

² Department of Chemistry, Faculty of Science, University of Zagreb, HR-10001 Zagreb, Croatia

Molecules 2017, 22(7), 1234; https://doi.org/10.3390/molecules22071234 - 22 Jul 2017

Cited by 28 | Viewed by 6427

Abstract

For the last six decades, researchers have been focused on finding efficient reactivators of organophosphorus compound (OP)-inhibited acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). In this study, we have focused our research on a new oxime scaffold based on the Cinchona structure since it was [...] Read more.

For the last six decades, researchers have been focused on finding efficient reactivators of organophosphorus compound (OP)-inhibited acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). In this study, we have focused our research on a new oxime scaffold based on the Cinchona structure since it was proven to fit the cholinesterases active site and reversibly inhibit their activity. Three Cinchona oximes (C1, C2, and C3), derivatives of the 9-oxocinchonidine, were synthesized and investigated in reactivation of various OP-inhibited AChE and BChE. As the results showed, the tested oximes were more efficient in the reactivation of BChE and they reactivated enzyme activity to up to 70% with reactivation rates similar to known pyridinium oximes used as antidotes in medical practice today. Furthermore, the oximes showed selectivity towards binding to the BChE active site and the determined enzyme-oxime dissociation constants supported work on the future development of inhibitors in other targeted studies (e.g., in treatment of neurodegenerative disease). Also, we monitored the cytotoxic effect of Cinchona oximes on two cell lines Hep G2 and SH-SY5Y to determine the possible limits for in vivo application. The cytotoxicity results support future studies of these compounds as long as their biological activity is targeted in the lower micromolar range. Full article

(This article belongs to the Special Issue The Cholinesterases—Structure, Mechanism, Function and Drug Design: The 25th Anniversary of the Solution of the Crystal Structure of Acetylcholinesterase by Joel L. Sussman and Israel Silman)

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4254 KiB

Open AccessArticle

Molecular Dynamics Simulations of the Host Defense Peptide Temporin L and Its Q3K Derivative: An Atomic Level View from Aggregation in Water to Bilayer Perturbation

by Andrea Farrotti¹, Paolo Conflitti¹, Saurabh Srivastava², Jimut Kanti Ghosh², Antonio Palleschi¹, Lorenzo Stella¹

and Gianfranco Bocchinfuso^1,*

¹ Dipartimento di Scienze e Tecnologie Chimiche, Università di Roma “Tor Vergata”, Rome 00133, Italy

² Molecular and Structural Biology Division, CSIR-Central Drug Research Institute, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India

Molecules 2017, 22(7), 1235; https://doi.org/10.3390/molecules22071235 - 22 Jul 2017

Cited by 13 | Viewed by 6721

Abstract

Temporin L (TempL) is a 13 residue Host Defense Peptide (HDP) isolated from the skin of frogs. It has a strong affinity for lipopolysaccharides (LPS), which is related to its high activity against Gram-negative bacteria and also to its strong tendency to neutralize [...] Read more.

Temporin L (TempL) is a 13 residue Host Defense Peptide (HDP) isolated from the skin of frogs. It has a strong affinity for lipopolysaccharides (LPS), which is related to its high activity against Gram-negative bacteria and also to its strong tendency to neutralize the pro-inflammatory response caused by LPS release from inactivated bacteria. A designed analog with the Q3K substitution shows an enhancement in both these activities. In the present paper, Molecular Dynamics (MD) simulations have been used to investigate the origin of these improved properties. To this end, we have studied the behavior of the peptides both in water solution and in the presence of LPS lipid-A bilayers, demonstrating that the main effect through which the Q3K substitution improves the peptide activities is the destabilization of peptide aggregates in water. Full article

(This article belongs to the Special Issue Biomolecular Simulations)

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Open AccessArticle

A Novel Brominated Alkaloid Securidine A, Isolated from the Marine Bryozoan Securiflustra securifrons

by Priyanka Michael^1,*,†

, Kine Ø. Hansen^1,*,†, Johan Isaksson², Jeanette H. Andersen¹

and Espen Hansen¹

¹ MARBIO, UiT–The Arctic University of Norway, Breivika, Tromsø N-9037, Norway

² Department of Chemistry, UiT–The Arctic University of Norway, Breivika, Tromsø N-9037, Norway

^† These authors contributed equally to this work.

Molecules 2017, 22(7), 1236; https://doi.org/10.3390/molecules22071236 - 23 Jul 2017

Cited by 12 | Viewed by 5392

Abstract

A novel brominated alkaloid, Securidine A, was isolated from the cold water marine bryozoan Securiflustra securifrons. Securidine A was isolated using semi-preparative HPLC, and the structure was elucidated by spectroscopic methods. The isolated Securidine A was tested for cytotoxic, antibacterial, and anti-diabetic [...] Read more.

A novel brominated alkaloid, Securidine A, was isolated from the cold water marine bryozoan Securiflustra securifrons. Securidine A was isolated using semi-preparative HPLC, and the structure was elucidated by spectroscopic methods. The isolated Securidine A was tested for cytotoxic, antibacterial, and anti-diabetic activities as well as for its potential for inhibition of biofilm formation. No significant biological activity was observed in the applied bioassays, thus expanded bioactivity profiling is required, in order to reveal any potential applications for Securidine A. Full article

(This article belongs to the Section Natural Products Chemistry)

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2951 KiB

Open AccessArticle

A Novel and Practical Chromatographic “Fingerprint-ROC-SVM” Strategy Applied to Quality Analysis of Traditional Chinese Medicine Injections: Using KuDieZi Injection as a Case Study

by Bin Yang¹, Yuan Wang¹, Lanlan Shan¹, Jingtao Zou², Yuanyuan Wu¹, Feifan Yang¹, Yani Zhang¹, Yubo Li^1,*

and Yanjun Zhang^3,*

¹ College of Traditional Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, 312 Anshan West Road, Tianjin 300193, China

² Tonghua Huaxia Pharmaceutical Co., Ltd., 3333 Tuanjie Road, Tonghua 134100, China

³ Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 312 Anshan West Road, Tianjin 300193, China

Molecules 2017, 22(7), 1237; https://doi.org/10.3390/molecules22071237 - 23 Jul 2017

Cited by 26 | Viewed by 5864

Abstract

Fingerprinting is widely and commonly used in the quality control of traditional Chinese medicine (TCM) injections. However, current studies informed that the fingerprint similarity evaluation was less sensitive and easily generated false positive results. For this reason, a novel and practical chromatographic “Fingerprint-ROC-SVM” [...] Read more.

Fingerprinting is widely and commonly used in the quality control of traditional Chinese medicine (TCM) injections. However, current studies informed that the fingerprint similarity evaluation was less sensitive and easily generated false positive results. For this reason, a novel and practical chromatographic “Fingerprint-ROC-SVM” strategy was established by using KuDieZi (KDZ) injection as a case study in the present article. Firstly, the chromatographic fingerprints of KDZ injection were obtained by UPLC and the common characteristic peaks were identified with UPLC/Q-TOF-MS under the same chromatographic conditions. Then, the receiver operating characteristic (ROC) curve was used to optimize common characteristic peaks by the AUCs value greater than 0.7. Finally, a support vector machine (SVM) model, with the accuracy of 97.06%, was established by the optimized characteristic peaks and applied to monitor the quality of KDZ injection. As a result, the established model could sensitively and accurately distinguish the qualified products (QPs) with the unqualified products (UPs), high-temperature processed samples (HTPs) and high-illumination processed samples (HIPs) of KDZ injection, and the prediction accuracy was 100.00%, 93.75% and 100.00%, respectively. Furthermore, through the comparison with other chemometrics methods, the superiority of the novel analytical strategy was more prominent. It indicated that the novel and practical chromatographic “Fingerprint-ROC-SVM” strategy could be further applied to facilitate the development of the quality analysis of TCM injections. Full article

(This article belongs to the Collection Herbal Medicine Research)

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Open AccessArticle

Quality Assessment of Gentiana rigescens from Different Geographical Origins Using FT-IR Spectroscopy Combined with HPLC

by Zhe Wu^1,2,3, Yanli Zhao^1,2, Ji Zhang^1,2 and Yuanzhong Wang^1,2,*

¹ Institute of Medicinal Plants, Yunnan Academy of Agricultural Sciences, Kunming 650200, China

² Yunnan Technical Center for Quality of Chinese Materia Medica, Kunming 650200, China

³ College of Traditional Chinese Medicine, Yunnan University of Traditional Chinese Medicine, Kunming 650500, China

Molecules 2017, 22(7), 1238; https://doi.org/10.3390/molecules22071238 - 24 Jul 2017

Cited by 30 | Viewed by 5294

Abstract

Gentiana rigescens is a precious herbal medicine in China because of its liver-protective and choleretic effects. A method for the qualitative identification and quantitative evaluation of G. rigescens from Yunnan Province, China, has been developed employing Fourier transform infrared (FT-IR) spectroscopy and high [...] Read more.

Gentiana rigescens is a precious herbal medicine in China because of its liver-protective and choleretic effects. A method for the qualitative identification and quantitative evaluation of G. rigescens from Yunnan Province, China, has been developed employing Fourier transform infrared (FT-IR) spectroscopy and high performance liquid chromatography (HPLC) with the aid of chemometrics such as partial least squares discriminant analysis (PLS-DA) and support vector machines (SVM) regression. Our results indicated that PLS-DA model could efficiently discriminate G. rigescens from different geographical origins. It was found that the samples which could not be determined accurately were in the margin or outside of the 95% confidence ellipses. Moreover, the result implied that geographical origins variation of root samples were more obvious than that of stems and leaves. The quantitative analysis was based on gentiopicroside content which was the main active constituent in G. rigescens. For the prediction of gentiopicroside, the performances of model based on the parameters selected through grid search algorithm (GS) with seven-fold cross validation were better than those based on genetic algorithm (GA) and particle swarm optimization algorithm (PSO). For the SVM-GS model, the result was satisfactory. FT-IR spectroscopy coupled with PLS-DA and SVM-GS can be an alternative strategy for qualitative identification and quantitative evaluation of G. rigescens. Full article

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1006 KiB

Open AccessFeature PaperReview

Role of G Protein-Coupled Receptors in the Regulation of Structural Plasticity and Cognitive Function

by Crystal C. Y. Leung¹ and Yung H. Wong^1,2,3,*

¹ Division of Life Science, Biotechnology Research Institute, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China

² State Key Laboratory of Molecular Neuroscience, Molecular Neuroscience Center, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China

³ Guangdong Provincial Key Laboratory of Brain Science, Disease and Drug Development, HKUST Shenzhen Research Institute, Shenzhen 518057, Guangdong, China

Molecules 2017, 22(7), 1239; https://doi.org/10.3390/molecules22071239 - 24 Jul 2017

Cited by 34 | Viewed by 15049

Abstract

Cognition and other higher brain functions are known to be intricately associated with the capacity of neural circuits to undergo structural reorganization. Structural remodelling of neural circuits, or structural plasticity, in the hippocampus plays a major role in learning and memory. Dynamic modifications [...] Read more.

Cognition and other higher brain functions are known to be intricately associated with the capacity of neural circuits to undergo structural reorganization. Structural remodelling of neural circuits, or structural plasticity, in the hippocampus plays a major role in learning and memory. Dynamic modifications of neuronal connectivity in the form of dendritic spine morphology alteration, as well as synapse formation and elimination, often result in the strengthening or weakening of specific neural circuits that determine synaptic plasticity. Changes in dendritic complexity and synapse number are mediated by cellular processes that are regulated by extracellular signals such as neurotransmitters and neurotrophic factors. As many neurotransmitters act on G protein-coupled receptors (GPCRs), it has become increasingly apparent that GPCRs can regulate structural plasticity through a myriad of G protein-dependent pathways and non-canonical signals. A thorough understanding of how GPCRs exert their regulatory influence on dendritic spine morphogenesis may provide new insights for treating cognitive impairment and decline in various age-related diseases. In this article, we review the evidence of GPCR-mediated regulation of structural plasticity, with a special emphasis on the involvement of common as well as distinct signalling pathways that are regulated by major neurotransmitters. Full article

(This article belongs to the Special Issue G-protein Coupled Receptor Structure and Function)

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