Molecules

8 pages, 310 KiB

Open AccessOpinion

Chemoinformatics in the New Era: From Molecular Dynamics to Systems Dynamics

by Guanyu Wang

Molecules 2016, 21(3), 71; https://doi.org/10.3390/molecules21030071 - 3 Mar 2016

Cited by 2 | Viewed by 4935

Chemoinformatics, due to its power in gathering information at the molecular level, has a wide array of important applications to biology, including fundamental biochemical studies and drug discovery and optimization. As modern “omics” based profiling and network based modeling and simulation techniques grow [...] Read more.

Chemoinformatics, due to its power in gathering information at the molecular level, has a wide array of important applications to biology, including fundamental biochemical studies and drug discovery and optimization. As modern “omics” based profiling and network based modeling and simulation techniques grow in sophistication, chemoinformatics now faces a great opportunity to include systems-level control mechanisms as one of its pillar components to extend and refine its various applications. This viewpoint article, through the example of computer aided targeting of the PI3K/Akt/mTOR pathway, outlines major steps of integrating systems dynamics simulations into molecular dynamics simulations to facilitate a higher level of chemoinformatics that would revolutionize drug lead optimization, personalized therapy, and possibly other applications. Full article

(This article belongs to the Special Issue Chemoinformatics)

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17 pages, 4052 KiB

Open AccessArticle

Novel Gold Nanoparticles Reduced by Sargassum glaucescens: Preparation, Characterization and Anticancer Activity

by Zahra Ajdari, Heshu Rahman, Kamyar Shameli, Rasedee Abdullah, Maaruf Abd Ghani, Swee Yeap, Sahar Abbasiliasi, Daniel Ajdari and Arbakariya Ariff

Molecules 2016, 21(3), 123; https://doi.org/10.3390/molecules21030123 - 1 Mar 2016

Cited by 55 | Viewed by 9846

Abstract

The current study investigated the anticancer properties of gold nanoparticles (SG-stabilized AuNPs) synthesized using water extracts of the brown seaweed Sargassum glaucescens (SG). SG-stabilized AuNPs were characterized by ultraviolet-visible spectroscopy, transmission and scanning electron microscopy, and energy dispersive X-ray fluorescence spectrometry. The SG-stabilized [...] Read more.

The current study investigated the anticancer properties of gold nanoparticles (SG-stabilized AuNPs) synthesized using water extracts of the brown seaweed Sargassum glaucescens (SG). SG-stabilized AuNPs were characterized by ultraviolet-visible spectroscopy, transmission and scanning electron microscopy, and energy dispersive X-ray fluorescence spectrometry. The SG-stabilized AuNPs were stable and small at 3.65 ± 1.69 nm in size. The in vitro anticancer effect of SG-stabilized AuNPs was determined on cervical (HeLa), liver (HepG2), breast (MDA-MB-231) and leukemia (CEM-ss) cell lines using fluorescence microscopy, flow cytometry, caspase activity determination, and MTT assays. After 72 h treatment, SG-stabilized AuNPs was shown to be significant (p < 0.05) cytotoxic to the cancer cells in a dose- and time-dependent manner. The IC₅₀ values of SG-stabilized AuNPs on the HeLa, HepG2, CEM-ss, MDA-MB-231 cell lines were 4.75 ± 1.23, 7.14 ± 1.45, 10.32 ± 1.5, and 11.82 ± 0.9 μg/mL, respectively. On the other hand, SG-stabilized AuNPs showed no cytotoxic effect towards the normal human mammary epithelial cells (MCF-10A). SG-stabilized AuNPs significantly (p < 0.05) arrest HeLa cell cycle at G2/M phase and significantly (p < 0.05) activated caspases-3 and -9 activities. The anticancer effect of SG-stabilized AuNPs is via the intrinsic apoptotic pathway. The study showed that SG-stabilized AuNPs is a good candidate to be developed into a chemotherapeutic compound for the treatment of cancers especially cervical cancer. Full article

(This article belongs to the Special Issue Pharmaceutical Nanotechnology: Novel Approaches)

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13 pages, 793 KiB

Open AccessArticle

Synthesis and Biological Evaluation of Novel Benzothiazole Derivatives as Potential Anticonvulsant Agents

by Da-Chuan Liu, Hong-Jian Zhang, Chun-Mei Jin and Zhe-Shan Quan

Molecules 2016, 21(3), 164; https://doi.org/10.3390/molecules21030164 - 29 Feb 2016

Cited by 48 | Viewed by 7354

Abstract

New benztriazoles with a mercapto-triazole and other heterocycle substituents were synthesized and evaluated for their anticonvulsant activity and neurotoxicity by using the maximal electroshock (MES), subcutaneous pentylenetetrazole (scPTZ), and rotarod neurotoxicity (TOX) tests. Among the compounds studied, compound 2-((1H-1,2,4-triazol-3-yl)thio)-N-(6-((3-fluorobenzyl) oxy)benzo[d]thiazol-2-yl)acetamide (5i) and 2-((1H-1,2,4-triazol-3-yl)thio)-N-(6-((4-fluorobenzyl)oxy) [...] Read more.

New benztriazoles with a mercapto-triazole and other heterocycle substituents were synthesized and evaluated for their anticonvulsant activity and neurotoxicity by using the maximal electroshock (MES), subcutaneous pentylenetetrazole (scPTZ), and rotarod neurotoxicity (TOX) tests. Among the compounds studied, compound 2-((1H-1,2,4-triazol-3-yl)thio)-N-(6-((3-fluorobenzyl) oxy)benzo[d]thiazol-2-yl)acetamide (5i) and 2-((1H-1,2,4-triazol-3-yl)thio)-N-(6-((4-fluorobenzyl)oxy) benzo[d] thiazol-2-yl)acetmide (5j) were the most potent, with an ED₅₀ value of 50.8 mg/kg and 54.8 mg/kg in the MES test and 76.0 mg/kg and 52.8 mg/kg in the scPTZ seizures test, respectively. They also showed lower neurotoxicity and, therefore a higher protective index. In particular, compound 5j showed high protective index (PI) values of 8.96 in the MES test and 9.30 in the scPTZ test, which were better than those of the standard drugs used as positive controls in this study. Full article

(This article belongs to the Special Issue Drug Design and Discovery: Principles and Applications)

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14 pages, 1083 KiB

Open AccessArticle

Transcriptome Sequencing and Development of Genic SSR Markers of an Endangered Chinese Endemic Genus Dipteronia Oliver (Aceraceae)

by Tao Zhou, Zhong-Hu Li, Guo-Qing Bai, Li Feng, Chen Chen, Yue Wei, Yong-Xia Chang and Gui-Fang Zhao

Molecules 2016, 21(3), 166; https://doi.org/10.3390/molecules21030166 - 23 Feb 2016

Cited by 32 | Viewed by 5686

Abstract

Dipteronia Oliver (Aceraceae) is an endangered Chinese endemic genus consisting of two living species, Dipteronia sinensis and Dipteronia dyeriana. However, studies on the population genetics and evolutionary analyses of Dipteronia have been hindered by limited genomic resources and genetic markers. [...] Read more.

Dipteronia Oliver (Aceraceae) is an endangered Chinese endemic genus consisting of two living species, Dipteronia sinensis and Dipteronia dyeriana. However, studies on the population genetics and evolutionary analyses of Dipteronia have been hindered by limited genomic resources and genetic markers. Here, the generation, de novo assembly and annotation of transcriptome datasets, and a large set of microsatellite or simple sequence repeat (SSR) markers derived from Dipteronia have been described. After Illumina pair-end sequencing, approximately 93.2 million reads were generated and assembled to yield a total of 99,358 unigenes. A majority of these unigenes (53%, 52,789) had at least one blast hit against the public protein databases. Further, 12,377 SSR loci were detected and 4179 primer pairs were designed for experimental validation. Of these 4179 primer pairs, 435 primer pairs were randomly selected to test polymorphism. Our results show that products from 132 primer pairs were polymorphic, in which 97 polymorphic SSR markers were further selected to analyze the genetic diversity of 10 natural populations of Dipteronia. The identification of SSR markers during our research will provide the much valuable data for population genetic analyses and evolutionary studies in Dipteronia. Full article

(This article belongs to the Section Molecular Diversity)

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10 pages, 1292 KiB

Open AccessCommunication

In Vivo Cardiotoxicity Induced by Sodium Aescinate in Zebrafish Larvae

by Jinfeng Liang, Wangdong Jin, Hongwen Li, Hongcui Liu, Yanfeng Huang, Xiaowen Shan, Chunqi Li, Letian Shan and Thomas Efferth

Molecules 2016, 21(3), 190; https://doi.org/10.3390/molecules21030190 - 23 Feb 2016

Cited by 22 | Viewed by 7476

Abstract

Sodium aescinate (SA) is a widely-applied triterpene saponin product derived from horse chestnut seeds, possessing vasoactive and organ-protective activities with oral or injection administration in the clinic. To date, no toxicity or adverse events in SA have been reported, by using routine models [...] Read more.

Sodium aescinate (SA) is a widely-applied triterpene saponin product derived from horse chestnut seeds, possessing vasoactive and organ-protective activities with oral or injection administration in the clinic. To date, no toxicity or adverse events in SA have been reported, by using routine models (in vivo or in vitro), which are insufficient to predict all aspects of its pharmacological and toxicological actions. In this study, taking advantage of transparent zebrafish larvae (Danio rerio), we evaluated cardiovascular toxicity of SA at doses of 1/10 MNLC, 1/3 MNLC, MNLC and LC10 by yolk sac microinjection. The qualitative and quantitative cardiotoxicity in zebrafish was assessed at 48 h post-SA treatment, using specific phenotypic endpoints: heart rate, heart rhythm, heart malformation, pericardial edema, circulation abnormalities, thrombosis and hemorrhage. The results showed that SA at 1/10 MNLC and above doses could induce obvious cardiac and pericardial malformations, whilst 1/3 MNLC and above doses could induce significant cardiac malfunctions (heart rate and circulation decrease/absence), as compared to untreated or vehicle-treated control groups. Such cardiotoxic manifestations occurred in more than 50% to 100% of all zebrafish treated with SA at MNLC and LC10. Our findings have uncovered the potential cardiotoxicity of SA for the first time, suggesting more attention to the risk of its clinical application. Such a time- and cost-saving zebrafish cardiotoxicity assay is very valid and reliable for rapid prediction of compound toxicity during drug research and development. Full article

(This article belongs to the Section Natural Products Chemistry)

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12 pages, 2339 KiB

Open AccessArticle

Cytotoxic 1,3-Thiazole and 1,2,4-Thiadiazole Alkaloids from Penicillium oxalicum: Structural Elucidation and Total Synthesis

by Zheng Yang, Nianyu Huang, Bang Xu, Wenfeng Huang, Tianpeng Xie, Fan Cheng and Kun Zou

Molecules 2016, 21(3), 232; https://doi.org/10.3390/molecules21030232 - 26 Feb 2016

Cited by 23 | Viewed by 6668

Abstract

Two new thiazole and thiadiazole alkaloids, penicilliumthiamine A and B (2 and 3), were isolated from the culture broth of Penicillium oxalicum, a fungus found in Acrida cinerea. Their structures were elucidated mainly by spectroscopic analysis, total synthesis and X-ray crystallographic [...] Read more.

Two new thiazole and thiadiazole alkaloids, penicilliumthiamine A and B (2 and 3), were isolated from the culture broth of Penicillium oxalicum, a fungus found in Acrida cinerea. Their structures were elucidated mainly by spectroscopic analysis, total synthesis and X-ray crystallographic analysis. Biological evaluations indicated that compound 1, 3a and 3 exhibit potent cytotoxicity against different cancer cell lines through inhibiting the phosphorylation of AKT/PKB (Ser 473), one of important cancer drugs target. Full article

(This article belongs to the Section Natural Products Chemistry)

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52 pages, 6441 KiB

Open AccessReview

Natural Products from Chinese Medicines with Potential Benefits to Bone Health

by Chun-Tao Che, Man Sau Wong and Christopher Wai Kei Lam

Molecules 2016, 21(3), 239; https://doi.org/10.3390/molecules21030239 - 27 Feb 2016

Cited by 90 | Viewed by 13865

Abstract

Osteoporosis is a progressive, systemic bone disorder characterized by loss of bone mass and microstructure, leading to reduced bone strength and increased risk of fracture. It is often associated with reduced quality of life and other medical complications. The disease is common in [...] Read more.

Osteoporosis is a progressive, systemic bone disorder characterized by loss of bone mass and microstructure, leading to reduced bone strength and increased risk of fracture. It is often associated with reduced quality of life and other medical complications. The disease is common in the aging population, particularly among postmenopausal women and patients who receive long-term steroidal therapy. Given the rapid growth of the aging population, increasing life expectancy, the prevalence of bone loss, and financial burden to the healthcare system and individuals, demand for new therapeutic agents and nutritional supplements for the management and promotion of bone health is pressing. With the advent of global interest in complementary and alternative medicine and natural products, Chinese medicine serves as a viable source to offer benefits for the improvement and maintenance of bone health. This review summarizes the scientific information obtained from recent literatures on the chemical ingredients of Chinese medicinal plants that have been reported to possess osteoprotective and related properties in cell-based and/or animal models. Some of these natural products (or their derivatives) may become promising leads for development into dietary supplements or therapeutic drugs. Full article

(This article belongs to the Collection Herbal Medicine Research)

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13 pages, 536 KiB

Open AccessArticle

New Bufadienolides Isolated from the Roots of Kalanchoe daigremontiana (Crassulaceae)

by Barbara Moniuszko-Szajwaj, Łukasz Pecio, Mariusz Kowalczyk and Anna Stochmal

Molecules 2016, 21(3), 243; https://doi.org/10.3390/molecules21030243 - 24 Feb 2016

Cited by 25 | Viewed by 6796

Abstract

An aqueous extract from the roots of Kalanchoe daigremontiana turned out to be a rich source of bufadienolides. The existing literature data relate mainly to the aerial parts of Kalanchoe but there is no information about the metabolic profile of the roots, which [...] Read more.

An aqueous extract from the roots of Kalanchoe daigremontiana turned out to be a rich source of bufadienolides. The existing literature data relate mainly to the aerial parts of Kalanchoe but there is no information about the metabolic profile of the roots, which are also used in traditional medicine. Our investigation concerning the roots of K. daigremontiana led to the isolation and characterization of eight new bufadienolides, namely 1β,3β,5β,14β,19-pentahydroxybufa-20,22-dienolide (1), 19-(acetyloxy)-1β,3β,5β,14β-tetrahydroxybufa-20,22-dienolide (2), 3β-O-α-l-rhamno-pyranosyl-5β,11α,14β,19-tetrahydroxybufa-20,22-dienolide (3), 19-(acetyloxy)-3β,5β,11α,14β-tetrahydroxybufa-20,22-dienolide (4), 3β,5β,11α,14β,19-pentahydroxy-12-oxo-bufa-20,22-dienolide (5), 19-(acetyloxy)-3β,5β,11α,14β-tetrahydroxy-12-oxo-bufa-20,22-dienolide (6), 19-(acetyloxy)-1β,3β,5β,11α,14β-pentahydroxy-12-oxo-bufa-20,22-dienolide (7) and 1β-(acetyloxy)-3β,5β,11α,14β,19-pentahydroxy-12-oxo-bufa-20,22-dienolide (8), together with seven known compounds: 11α,19-dihydroxytelocinobufagin (9), bersaldegenin-1-acetate (10), daigredorigenin-3-acetate (11), bersaldegenin-1,3,5-orthoacetate (12), bryotoxin B (13), bryophyllin B (14) and bersaldegenin (15). The structures were established applying extensive 1D- and 2D-NMR and MS spectroscopic analyses. Full article

(This article belongs to the Section Metabolites)

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15 pages, 3036 KiB

Open AccessArticle

Phenolic Compounds in Chilean Mistletoe (Quintral, Tristerix tetrandus) Analyzed by UHPLC–Q/Orbitrap/MS/MS and Its Antioxidant Properties

by Mario J. Simirgiotis, Cristina Quispe, Carlos Areche and Beatriz Sepúlveda

Molecules 2016, 21(3), 245; https://doi.org/10.3390/molecules21030245 - 23 Feb 2016

Cited by 60 | Viewed by 8684

Abstract

Mass spectrometry has become a method of choice to characterize bioactive compounds in biological samples because of its sensitivity and selectivity. Hybrid ultra-HPLC hyphenated with Orbitrap mass analyzer is an innovative state of the art technology that allows fast and accurate metabolomic analyses. [...] Read more.

Mass spectrometry has become a method of choice to characterize bioactive compounds in biological samples because of its sensitivity and selectivity. Hybrid ultra-HPLC hyphenated with Orbitrap mass analyzer is an innovative state of the art technology that allows fast and accurate metabolomic analyses. In this work the metabolites of a Chilean mistletoe endemic to the VIII region of Chile were investigated for the first time using UHPLC mass analysis (UHPLC-PDA-HESI-Orbitrap MSⁿ). The anthocyanins, together with the non-pigmented phenolics were fingerprinted and correlated with the antioxidant capacities measured by the bleaching of the DPPH radical, the ferric reducing antioxidant power (FRAP), the superoxide anion scavenging activity assay (SA), and total content of phenolics, flavonoids and anthocyanins measured by spectroscopic methods. Six anthocyanins were identified, and among them, the 3-O-glycosides of delphinidin and cyanidin were the major ones. In addition, several phenolic acids (including feruloylquinic acid, feruloyl glucose, chlorogenic acid) and several flavonols (luteolin, quercetin, apigenin, isorhamnetin and glycoside derivatives) were also identified. The mistletoe leaves showed the highest antioxidant activity as measured by the DPPH radical bleaching, ferric reducing antioxidant power and superoxide anion scavenging activity tests (13.38 ± 0.47 µg/mL, 125.32 ± 5.96 µmolTE/g DW and 84.06 ± 4.59 at 100 µg/mL, respectively). Full article

(This article belongs to the Section Natural Products Chemistry)

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16 pages, 2481 KiB

Open AccessArticle

Exotic Vegetable Oils for Cosmetic O/W Nanoemulsions: In Vivo Evaluation

by Tatiana A. Pereira, Carolina M. Guerreiro, Monica Maruno, Marcio Ferrari and Pedro Alves Rocha-Filho

Molecules 2016, 21(3), 248; https://doi.org/10.3390/molecules21030248 - 24 Feb 2016

Cited by 30 | Viewed by 7976

Abstract

Oil-in-water nanoemulsions are stable systems with droplet sizes in the 20–200 nm range. The physicochemical properties of these systems may be influenced by the addition of additives. Thus, the influence of ethoxylated (EL) and acetylated lanolin (AL) addition on the droplet size, pH [...] Read more.

Oil-in-water nanoemulsions are stable systems with droplet sizes in the 20–200 nm range. The physicochemical properties of these systems may be influenced by the addition of additives. Thus, the influence of ethoxylated (EL) and acetylated lanolin (AL) addition on the droplet size, pH values, electrical conductivity and stability of nanoemulsions was investigated. Then, effect of nano-emulsions additives with EL (NE-EL) or AL (NE-AL) in hydration, oiliness and pH of the skin were evaluated. Nanoemulsion safety was evaluated through the observation of no undesirable effects after skin formulation application. Both additives caused changes in droplet size and electrical conductivity, but not in pH values. Nanoemulsions containing up to 6.0% ethoxylated lanolin and 2.0% acetylated lanolin remained stable after centrifugation tests. Higher concentrations of the additives made the nanoemulsions unstable. Stability tests showed that ethoxylated lanolin produced more stable nanoemulsions then acetylated lanolin and that the major instability phenomenon occurring in these systems is coalescence at elevated temperatures. Nanoemulsion-based lanolin derivatives increased skin hydration and oiliness and did not change cutaneous pH values. These formulations are non-toxic since they did not cause any irritation on the skin surface after nanoemulsion application, showing potential as carriers for pharmaceuticals and cosmetic applications. Full article

(This article belongs to the Special Issue Pharmaceutical Nanotechnology: Novel Approaches)

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8 pages, 951 KiB

Open AccessArticle

Synthesis of 5,10-bis(Trifluoromethyl) Substituted β-Octamethylporphyrins and Central-Metal-Dependent Solvolysis of Their meso-Trifluoromethyl Groups

by Masaaki Suzuki, Saburo Neya and Yutaka Nishigaichi

Molecules 2016, 21(3), 252; https://doi.org/10.3390/molecules21030252 - 23 Feb 2016

Cited by 11 | Viewed by 5364

Abstract

5,10-Bistrifluoromethyl substituted β-octamethylporphyrins were synthesized via a scrambling side reaction of a dipyrromethane precursor in the presence of a large excess of trifluoroacetic acid. Compared with the trans-analogs, the cis-analogs of meso-trifluoromethyl β-octaalkylporphyrin showed more red-shifted absorption bands. These meso [...] Read more.

5,10-Bistrifluoromethyl substituted β-octamethylporphyrins were synthesized via a scrambling side reaction of a dipyrromethane precursor in the presence of a large excess of trifluoroacetic acid. Compared with the trans-analogs, the cis-analogs of meso-trifluoromethyl β-octaalkylporphyrin showed more red-shifted absorption bands. These meso-trifluoromethyl derivatives of β-octaalkylporphyrins underwent smooth metalation, similar to other common porphyrins, however, the corresponding zinc complexes underwent a type of solvolysis, whereby the trifluoromethyl groups were converted into methoxycarbonyl groups by the methanol used as solvent. UV-visible absorption spectra and X-ray crystal structure analyses revealed that the presence of a methoxycarbonyl substituent did not influence the deformation of the molecular framework and its absorption properties; this is because the methoxycarbonyl has a planar and perpendicular geometry, as opposed to the relatively bulky trifluoromethyl substituent. Full article

(This article belongs to the Special Issue Tetrapyrrolic Macrocycles: Synthesis, Functionalization and Applications)

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14 pages, 2391 KiB

Open AccessReview

Heterogeneous Phase Microwave-Assisted Reactions under CO₂ or CO Pressure

by Emanuela Calcio Gaudino, Laura Rinaldi, Laura Rotolo, Diego Carnaroglio, Camillo Pirola and Giancarlo Cravotto

Molecules 2016, 21(3), 253; https://doi.org/10.3390/molecules21030253 - 24 Feb 2016

Cited by 9 | Viewed by 6169

Abstract

The present review deals with the recent achievements and impressive potential applications of microwave (MW) heating to promote heterogeneous reactions under gas pressure. The high versatility of the latest generation of professional reactors combines extreme reaction conditions with safer and more efficient protocols. [...] Read more.

The present review deals with the recent achievements and impressive potential applications of microwave (MW) heating to promote heterogeneous reactions under gas pressure. The high versatility of the latest generation of professional reactors combines extreme reaction conditions with safer and more efficient protocols. The double aims of this survey are to provide a panoramic snapshot of MW-assisted organic reactions with gaseous reagents, in particular CO and CO₂, and outline future applications. Stubborn and time-consuming carbonylation-like heterogeneous reactions, which have not yet been studied under dielectric heating, may well find an outstanding ally in the present protocol. Full article

(This article belongs to the Special Issue Microwave-Assisted Organic Synthesis)

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13 pages, 4121 KiB

Open AccessArticle

Preparation and Biological Evaluation of Two Novel Platinum(II) Complexes Based on the Ligands of Dipicolyamine Bisphosphonate Esters

by Ling Qiu, Hong Liu, Ke Li, Gaochao Lv, Hui Yang, Xiaofeng Qin and Jianguo Lin

Molecules 2016, 21(3), 255; https://doi.org/10.3390/molecules21030255 - 24 Feb 2016

Cited by 8 | Viewed by 6139

Abstract

Two new platinum(II)-based complexes bearing a bone-targeting group were synthesized and characterized. They both have excellent affinity for hydroxyapatite (HA), which is abundant in human bone tissues. Their antitumor activities against five human cancer cell lines (U2OS, A549, HCT116, MDA-MB-231 and HepG2) were [...] Read more.

Two new platinum(II)-based complexes bearing a bone-targeting group were synthesized and characterized. They both have excellent affinity for hydroxyapatite (HA), which is abundant in human bone tissues. Their antitumor activities against five human cancer cell lines (U2OS, A549, HCT116, MDA-MB-231 and HepG2) were evaluated and compared with cisplatin (CDDP). Though the antitumor efficacies of new complexes are lower than that of CDDP, they show higher selectivity against the HepG2 hepatoma cell line than the L02 normal liver cell line. Morphology studies exhibited typical characteristics of cell apoptosis and the cell cycle distribution analysis indicated that the complexes can inhibit cancer cells by inducing cell cycle arrest at the G2/M phase, a similar mechanism of action to CDDP. 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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11 pages, 1039 KiB

Open AccessArticle

Chitosan Nanoparticles as Carriers for the Delivery of ΦKAZ14 Bacteriophage for Oral Biological Control of Colibacillosis in Chickens

by Adamu Ahmad Kaikabo, AbdulKarim Sabo Mohammed and Farida Abas

Molecules 2016, 21(3), 256; https://doi.org/10.3390/molecules21030256 - 14 Mar 2016

Cited by 27 | Viewed by 6296

Abstract

The use of chitosan as a delivery carrier has attracted much attention in recent years. In this study, chitosan nanoparticles (CS-NP) and chitosan-ΦKAZ14 bacteriophage-loaded nanoparticles (C-ΦKAZ14 NP) were prepared by a simple coercavation method and characterized. The objective was to achieve an effective [...] Read more.

The use of chitosan as a delivery carrier has attracted much attention in recent years. In this study, chitosan nanoparticles (CS-NP) and chitosan-ΦKAZ14 bacteriophage-loaded nanoparticles (C-ΦKAZ14 NP) were prepared by a simple coercavation method and characterized. The objective was to achieve an effective protection of bacteriophage from gastric acids and enzymes in the chicken gastrointestinal tract. The average particle sizes for CS-NP and C-ΦKAZ14 NP were 188 ± 7.4 and 176 ± 3.2 nm, respectively. The zeta potentials for CS-NP and C-ΦKAZ14 NP were 50 and 60 mV, respectively. Differential scanning calorimetry (DSC) of C-ΦKAZ14 NP gave an onset temperature of −17.17 °C with a peak at 17.32 °C and final end set of 17.41 °C, while blank chitosan NP had an onset of −20.00 °C with a peak at −19.78 °C and final end set at −20.47. FT-IR spectroscopy data of both CS-NP and C-ΦKAZ14 NP were the same. Chitosan nanoparticles showed considerable protection of ΦKAZ14 bacteriophage against degradation by enzymes as evidenced in gel electrophoresis, whereby ΦKAZ14 bacteriophage encapsulated in chitosan nanoparticles were protected whereas the naked ΦKAZ14 bacteriophage were degraded. C-ΦKAZ14 NP was non-toxic as shown by a chorioallantoic membrane (CAM) toxicity assay. It was concluded that chitosan nanoparticles could be a potent carrier of ΦKAZ14 bacteriophage for oral therapy against colibacillosis in poultry. Full article

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

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32 pages, 604 KiB

Open AccessReview

Potential Use of Turkish Medicinal Plants in the Treatment of Various Diseases

by Gulay Ozkan, Senem Kamiloglu, Tugba Ozdal, Dilek Boyacioglu and Esra Capanoglu

Molecules 2016, 21(3), 257; https://doi.org/10.3390/molecules21030257 - 25 Feb 2016

Cited by 74 | Viewed by 15122

Abstract

Medicinal plants are sources of health-promoting substances, including phytochemicals and phytoalexins that comprise polyphenols, flavonoids, carotenoids, vitamins A, C, E and several other constituents. Many studies have indicated that medicinal plants have been used to treat human diseases for thousands of years owing [...] Read more.

Medicinal plants are sources of health-promoting substances, including phytochemicals and phytoalexins that comprise polyphenols, flavonoids, carotenoids, vitamins A, C, E and several other constituents. Many studies have indicated that medicinal plants have been used to treat human diseases for thousands of years owing to their antimicrobial and antioxidant activities. Medicinal plants reduce the oxidative stress in cells and prevent cancer, cardiovascular and inflammatory diseases, neurodegenerative and digestive system disorders. These potential beneficial effects have been attributed to the presence of bioactive compounds that show antioxidant properties by acting as free radical scavengers or metal chelators, reducing the reactions that produce reactive oxygen and nitrogen species (ROS/RNS). Considering the importance of medicinal plants in terms of their beneficial health effects, some of the medicinally important plants grown in Turkey are covered in this review with respect to their antioxidant potential and phytochemical profile. Full article

(This article belongs to the Special Issue 20th Anniversary of Molecules—Recent Advances in Natural Products)

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10 pages, 1158 KiB

Open AccessArticle

Typical Monoterpenes as Insecticides and Repellents against Stored Grain Pests

by Suelen L. Reis, Anieli G. Mantello, Jeferson M. Macedo, Erica A. Gelfuso, Cássio P. Da Silva, Ana L. Fachin, Alexandre M. Cardoso and Rene O. Beleboni

Molecules 2016, 21(3), 258; https://doi.org/10.3390/molecules21030258 - 23 Feb 2016

Cited by 71 | Viewed by 7134

Abstract

Five monoterpenes naturally occurring in essential oils were tested for their insecticidal and repellent activities against the bruchid beetle Callosobruchus maculatus and the maize weevil Sitophilus zeamais. The monoterpenes were highly efficient as inducers of mortality or repellency against both insect species. [...] Read more.

Five monoterpenes naturally occurring in essential oils were tested for their insecticidal and repellent activities against the bruchid beetle Callosobruchus maculatus and the maize weevil Sitophilus zeamais. The monoterpenes were highly efficient as inducers of mortality or repellency against both insect species. They were more efficient in their fumigant activity against C. maculatus than against S. zeamais, while this profile of action was inverted when considering the repellent activities. Eugenol was one the most effective fumigants against both insects and one the most effective repellent against C. maculatus, while citronellal and geranial were one the most effective repellents against S. zeamais. Functional and positional isomerism of the monoterpenes pairs appears to exert little or no influence on theirs effects, especially in case of repellency. The validation of the insecticidal/repellent efficacy of isolated monoterpenes may permit a more advantageous, rapid, economic and optimized approach to the identification of promising oils for commercial formulations when combined with ethnobotanical strategies. Full article

(This article belongs to the Section Natural Products Chemistry)

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13 pages, 1540 KiB

Open AccessArticle

Statistical Correlations between HPLC Activity-Based Profiling Results and NMR/MS Microfraction Data to Deconvolute Bioactive Compounds in Mixtures

by Samuel Bertrand, Antonio Azzollini, Andreas Nievergelt, Julien Boccard, Serge Rudaz, Muriel Cuendet and Jean-Luc Wolfender

Molecules 2016, 21(3), 259; https://doi.org/10.3390/molecules21030259 - 24 Feb 2016

Cited by 13 | Viewed by 7248

Abstract

Recent approaches in natural product (NP) research are leading toward the discovery of bioactive chemical entities at the microgram level. In comparison to classical large scale bioassay-guided fractionation, the use of LC-MS metabolite profiling in combination with microfractionation for both bioactivity profiling and [...] Read more.

Recent approaches in natural product (NP) research are leading toward the discovery of bioactive chemical entities at the microgram level. In comparison to classical large scale bioassay-guided fractionation, the use of LC-MS metabolite profiling in combination with microfractionation for both bioactivity profiling and NMR analysis, allows the identification of bioactive compounds at a very early stage. In that context, this study aims to assess the potential of statistic correlation analysis to enable unambiguous identification of features related to bioactive compounds in mixtures, without the need for complete isolation. For that purpose, a mixture of NPs was microfractionated by rapid small-scale semi-preparative HPLC for proof-of-concept. UHPLC-ESI-TOFMS profiles, micro-flow CapNMR spectra and a cancer chemopreventive assay carried out on every microfraction were analysed by statistical correlations. Full article

(This article belongs to the Special Issue Applications of Metabolomics within Natural Products Chemistry)

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17 pages, 3863 KiB

Open AccessArticle

Antidepressant Potential of Chlorogenic Acid-Enriched Extract from Eucommia ulmoides Oliver Bark with Neuron Protection and Promotion of Serotonin Release through Enhancing Synapsin I Expression

by Jianming Wu, Haixia Chen, Hua Li, Yong Tang, Le Yang, Shousong Cao and Dalian Qin

Molecules 2016, 21(3), 260; https://doi.org/10.3390/molecules21030260 - 25 Feb 2016

Cited by 74 | Viewed by 9012

Abstract

Eucommia ulmoides Oliver (E. ulmoides) is a traditional Chinese medicine with many beneficial effects, used as a tonic medicine in China and other countries. Chlorogenic acid (CGA) is an important compound in E. ulmoides with neuroprotective, cognition improvement and other pharmacological [...] Read more.

Eucommia ulmoides Oliver (E. ulmoides) is a traditional Chinese medicine with many beneficial effects, used as a tonic medicine in China and other countries. Chlorogenic acid (CGA) is an important compound in E. ulmoides with neuroprotective, cognition improvement and other pharmacological effects. However, it is unknown whether chlorogenic acid-enriched Eucommia ulmoides Oliver bark has antidepressant potential through neuron protection, serotonin release promotion and penetration of blood-cerebrospinal fluid barrier. In the present study, we demonstrated that CGA could stimulate axon and dendrite growth and promote serotonin release through enhancing synapsin I expression in the cells of fetal rat raphe neurons in vitro. More importantly, CGA-enriched extract of E. ulmoides (EUWE) at 200 and 400 mg/kg/day orally administered for 7 days showed antidepressant-like effects in the tail suspension test of KM mice. Furthermore, we also found CGA could be detected in the the cerebrospinal fluid of the rats orally treated with EUWE and reach the level of pharmacological effect for neuroprotection by UHPLC-ESI-MS/MS. The findings indicate CGA is able to cross the blood-cerebrospinal fluid barrier to exhibit its neuron protection and promotion of serotonin release through enhancing synapsin I expression. This is the first report of the effect of CGA on promoting 5-HT release through enhancing synapsin I expression and CGA-enriched EUWE has antidepressant-like effect in vivo. EUWE may be developed as the natural drugs for the treatment of depression. Full article

(This article belongs to the Special Issue Potential Neuromodulatory Profile of Phytocompounds in Brain Disorders)

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9 pages, 1789 KiB

Open AccessArticle

Au-Based Catalysts: Electrochemical Characterization for Structural Insights

by Valentina Pifferi, Carine E. Chan-Thaw, Sebastiano Campisi, Anna Testolin, Alberto Villa, Luigi Falciola and Laura Prati

Molecules 2016, 21(3), 261; https://doi.org/10.3390/molecules21030261 - 25 Feb 2016

Cited by 11 | Viewed by 5564

Abstract

Au-based catalysts are widely used in important processes because of their peculiar characteristics. The catalyst performance depends strongly on the nature and structure of the metal nanoparticles, especially in the case of bimetallic catalysts where synergistic effects between the two metals can be [...] Read more.

Au-based catalysts are widely used in important processes because of their peculiar characteristics. The catalyst performance depends strongly on the nature and structure of the metal nanoparticles, especially in the case of bimetallic catalysts where synergistic effects between the two metals can be occasionally seen. In this paper, it is shown that electrochemical characterisation (cyclovoltammetry CV and electrochemical impedance spectroscopy EIS) of AuPd systems can be used to determine the presence of an electronic interaction between the two metals, thus providing a strong support in the determination of the nature of the synergy between Au and Pd in the liquid phase oxidation of alcohols. However, it seems likely that the strong difference in the catalytic behavior between the single metals and the bimetallic system is connected not only to the redox behaviour, but also to the energetic balance between the different elementary steps of the reaction. Full article

(This article belongs to the Special Issue Coinage Metal (Copper, Silver, and Gold) Catalysis)

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11 pages, 2102 KiB

Open AccessArticle

Extraction, Preconcentration and Isolation of Flavonoids from Apocynum venetum L. Leaves Using Ionic Liquid-Based Ultrasonic-Assisted Extraction Coupled with an Aqueous Biphasic System

by Zhijian Tan, Yongjian Yi, Hongying Wang, Wanlai Zhou and Chaoyun Wang

Molecules 2016, 21(3), 262; https://doi.org/10.3390/molecules21030262 - 4 Mar 2016

Cited by 60 | Viewed by 8691

Abstract

Background: Ionic liquids (ILs) are considered as green solvents, and widely applied for the extraction of various compounds. Methods: The present research focuses on the extraction of flavonoids from Apocynum venetum L. leaves by ultrasound-assisted extraction (UAE). Several major influencing factors [...] Read more.

Background: Ionic liquids (ILs) are considered as green solvents, and widely applied for the extraction of various compounds. Methods: The present research focuses on the extraction of flavonoids from Apocynum venetum L. leaves by ultrasound-assisted extraction (UAE). Several major influencing factors were optimized. Then, an aqueous biphasic system (ABS) was applied for further isolation of flavonoids. Results: The flavonoids were mainly distributed in the top phase, while impurities were extracted to the bottom phase. The parameters influencing the extraction, namely type and concentration of salt, temperature, and pH, were studied in detail. Under optimized conditions (72.43% IL extract, 28.57% (NH₄)₂SO₄, 25 °C temperature, pH 4.5), the preconcentration factor and extraction efficiency were found to be 3.78% and 93.35%, respectively. Conclusions: This simple and efficient methodology is expected to see great use in the extraction and isolation of pharmaceutically active components from medicinal plant resources. Full article

(This article belongs to the Section Natural Products Chemistry)

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4 pages, 518 KiB

Open AccessArticle

An Efficient Chemical Synthesis of Scutellarein: An in Vivo Metabolite of Scutellarin

by Ze-Xi Dong, Nian-Guang Li, Peng-Xuan Zhang, Ting Gu, Wen-Yu Wu and Zhi-Hao Shi

Molecules 2016, 21(3), 263; https://doi.org/10.3390/molecules21030263 - 25 Feb 2016

Cited by 13 | Viewed by 5960

Abstract

Scutellarein (2), which is an important in vivo metabolite of scutellarin (1), was synthesized from 3,4,5-trimethoxyphenol (3) in high yield in four steps. This strategy relies on acetylation, aldolization, cyclization and hydrolysis reactions, respectively. Full article

(This article belongs to the Section Metabolites)

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22 pages, 1376 KiB

Open AccessReview

Curcumin and Health

by Mario Pulido-Moran, Jorge Moreno-Fernandez, Cesar Ramirez-Tortosa and MCarmen Ramirez-Tortosa

Molecules 2016, 21(3), 264; https://doi.org/10.3390/molecules21030264 - 25 Feb 2016

Cited by 466 | Viewed by 52299

Abstract

Nowadays, there are some molecules that have shown over the years a high capacity to act against relevant pathologies such as cardiovascular disease, neurodegenerative disorders or cancer. This article provides a brief review about the origin, bioavailability and new research on curcumin and [...] Read more.

Nowadays, there are some molecules that have shown over the years a high capacity to act against relevant pathologies such as cardiovascular disease, neurodegenerative disorders or cancer. This article provides a brief review about the origin, bioavailability and new research on curcumin and synthetized derivatives. It examines the beneficial effects on health, delving into aspects such as cancer, cardiovascular effects, metabolic syndrome, antioxidant capacity, anti-inflammatory properties, and neurological, liver and respiratory disorders. Thanks to all these activities, curcumin is positioned as an interesting nutraceutical. This is the reason why it has been subjected to several modifications in its structure and administration form that have permitted an increase in bioavailability and effectiveness against different diseases, decreasing the mortality and morbidity associated to these pathologies. Full article

(This article belongs to the Special Issue 20th Anniversary of Molecules—Recent Advances in Natural Products)

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10 pages, 2724 KiB

Open AccessArticle

Silymarin-Loaded Nanoparticles Based on Stearic Acid-Modified Bletilla striata Polysaccharide for Hepatic Targeting

by Yanni Ma, Shaolong He, Xueqin Ma, Tongtong Hong, Zhifang Li, Kinam Park and Wenping Wang

Molecules 2016, 21(3), 265; https://doi.org/10.3390/molecules21030265 - 29 Feb 2016

Cited by 41 | Viewed by 6410

Abstract

Silymarin has been widely used as a hepatoprotective drug in the treatment of various liver diseases, yet its effectiveness is affected by its poor water solubility and low bioavailability after oral administration, and there is a need for the development of intravenous products, [...] Read more.

Silymarin has been widely used as a hepatoprotective drug in the treatment of various liver diseases, yet its effectiveness is affected by its poor water solubility and low bioavailability after oral administration, and there is a need for the development of intravenous products, especially for liver-targeting purposes. In this study, silymarin was encapsulated in self-assembled nanoparticles of Bletilla striata polysaccharide (BSP) conjugates modified with stearic acid and the physicochemical properties of the obtained nanoparticles were characterized. The silymarin-loaded micelles appeared as spherical particles with a mean diameter of 200 nm under TEM. The encapsulation of drug molecules was confirmed by DSC thermograms and XRD diffractograms, respectively. The nanoparticles exhibited a sustained-release profile for nearly 1 week with no obvious initial burst. Compared to drug solutions, the drug-loaded nanoparticles showed a lower viability and higher uptake intensity on HepG2 cell lines. After intravenous administration of nanoparticle formulation for 30 min to mice, the liver became the most significant organ enriched with the fluorescent probe. These results suggest that BSP derivative nanoparticles possess hepatic targeting capability and are promising nanocarriers for delivering silymarin to the liver. Full article

(This article belongs to the Section Medicinal Chemistry)

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17 pages, 6380 KiB

Open AccessArticle

Synthesis of N-(6-Arylbenzo[d]thiazole-2-acetamide Derivatives and Their Biological Activities: An Experimental and Computational Approach

by Yasmeen Gull, Nasir Rasool, Mnaza Noreen, Ataf Ali Altaf, Syed Ghulam Musharraf, Muhammad Zubair, Faiz-Ul-Hassan Nasim, Asma Yaqoob, Vincenzo DeFeo and Muhammad Zia-Ul-Haq

Molecules 2016, 21(3), 266; https://doi.org/10.3390/molecules21030266 - 25 Feb 2016

Cited by 37 | Viewed by 6855

Abstract

A new series of N-(6-arylbenzo[d]thiazol-2-yl)acetamides were synthesized by C-C coupling methodology in the presence of Pd(0) using various aryl boronic pinacol ester/acids. The newly synthesized compounds were evaluated for various biological activities like antioxidant, haemolytic, antibacterial and urease inhibition. In bioassays these [...] Read more.

A new series of N-(6-arylbenzo[d]thiazol-2-yl)acetamides were synthesized by C-C coupling methodology in the presence of Pd(0) using various aryl boronic pinacol ester/acids. The newly synthesized compounds were evaluated for various biological activities like antioxidant, haemolytic, antibacterial and urease inhibition. In bioassays these compounds were found to have moderate to good activities. Among the tested biological activities screened these compounds displayed the most significant activity for urease inhibition. In urease inhibition, all compounds were found more active than the standard used. The compound N-(6-(p-tolyl)benzo[d]thiazol-2-yl)acetamide was found to be the most active. To understand this urease inhibition, molecular docking studies were performed. The in silico studies showed that these acetamide derivatives bind to the non-metallic active site of the urease enzyme. Structure-activity studies revealed that H-bonding of compounds with the enzyme is important for its inhibition. Full article

(This article belongs to the Section Medicinal Chemistry)

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16 pages, 1573 KiB

Open AccessArticle

Synthesis of Naphthalene-Based Push-Pull Molecules with a Heteroaromatic Electron Acceptor

by David Šarlah, Amadej Juranovič, Boris Kožar, Luka Rejc, Amalija Golobič and Andrej Petrič

Molecules 2016, 21(3), 267; https://doi.org/10.3390/molecules21030267 - 2 Mar 2016

Cited by 10 | Viewed by 10043

Abstract

Naphthalene derivatives bearing electron-accepting and electron-donating groups at the 2,6-positions belong to the family of D-π-A push-pull dyes. It has been found that these compounds, e.g., 2-(1-(6-((2-(fluoro)ethyl)(methyl)amino)naphthalen-2-yl)ethylidene)malononitrile (FDDNP), show not only interesting optical properties, such as solvatochromism, but they have the potential to [...] Read more.

Naphthalene derivatives bearing electron-accepting and electron-donating groups at the 2,6-positions belong to the family of D-π-A push-pull dyes. It has been found that these compounds, e.g., 2-(1-(6-((2-(fluoro)ethyl)(methyl)amino)naphthalen-2-yl)ethylidene)malononitrile (FDDNP), show not only interesting optical properties, such as solvatochromism, but they have the potential to label protein aggregates of different compositions formed in the brain of patients suffering from neurodegenerative diseases like Alzheimer’s (AD). In continuation of our research we set our goal to find new FDDNP analogs, which would inherit optical and binding properties but hopefully show better specificity for tau protein aggregates, which are characteristic for neurodegeneration caused by repetitive mild trauma. In this work we report on the synthesis of new FDDNP analogs in which the acceptor group has been formally replaced with an aromatic five- or six-membered heterocycle. The heterocyclic moiety was annealed to the central naphthalene ring either by classical ring closure reactions or by modern transition metal-catalyzed coupling reactions. The chemical characterization, NMR spectra, and UV/vis properties of all new compounds are reported. Full article

(This article belongs to the Collection Heterocyclic Compounds)

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12 pages, 2086 KiB

Open AccessArticle

Solanum nigrum Protects against Hepatic Fibrosis via Suppression of Hyperglycemia in High-Fat/Ethanol Diet-Induced Rats

by Cheng-Jeng Tai, Chen-Yen Choong, Yeu-Ching Shi, Yu-Chun Lin, Chia-Woei Wang, Bao-Hong Lee and Chen-Jei Tai

Molecules 2016, 21(3), 269; https://doi.org/10.3390/molecules21030269 - 25 Feb 2016

Cited by 22 | Viewed by 6316

Abstract

Background: Advanced glycation end products (AGEs) signal through the receptor for AGE (RAGE), which can lead to hepatic fibrosis in hyperglycemia and hyperlipidemia. We investigated the inhibitory effect of aqueous extracts from Solanum nigrum (AESN) on AGEs-induced RAGE signaling and activation of hepatic [...] Read more.

Background: Advanced glycation end products (AGEs) signal through the receptor for AGE (RAGE), which can lead to hepatic fibrosis in hyperglycemia and hyperlipidemia. We investigated the inhibitory effect of aqueous extracts from Solanum nigrum (AESN) on AGEs-induced RAGE signaling and activation of hepatic stellate cells (HSCs) and hyperglycemia induced by high-fat diet with ethanol. Methods: An animal model was used to evaluate the anti-hepatic fibrosis activity of AESN in rats fed a high-fat diet (HFD; 30%) with ethanol (10%). Male Wistar rats (4 weeks of age) were randomly divided into four groups (n = 6): (1) control (basal diet); (2) HFD (30%) + ethanol (10%) (HFD/ethanol); (3) HFD/ethanol + AESN (100 mg/kg, oral administration); and (4) HFD/ethanol + pioglitazone (10 mg/kg, oral administration) and treated with HFD for 6 months in the presence or absence of 10% ethanol in dietary water. Results: We found that AESN improved insulin resistance and hyperinsulinemia, and downregulated lipogenesis via regulation of the peroxisome proliferator-activated receptor α (PPARα), PPARγ co-activator (PGC-1α), carbohydrate response element-binding protein (ChREBP), acetyl-CoA carboxylase (ACC), and fatty acid synthase (FAS) mRNA levels in the liver of HFD/ethanol-treated rats. In turn, AESN may delay and inhibit the progression of hepatic fibrosis, including α-smooth muscle actin (α-SMA) inhibition and MMP-2 production. Conclusions: These results suggest that AESN may be further explored as a novel anti-fibrotic strategy for the prevention of liver disease. Full article

(This article belongs to the Section Natural Products Chemistry)

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12 pages, 2884 KiB

Open AccessArticle

Rapid Authentication of the Herbal Medicine Plant Species Aralia continentalis Kitag. and Angelica biserrata C.Q. Yuan and R.H. Shan Using ITS2 Sequences and Multiplex-SCAR Markers

by Wook Jin Kim, Byeong Cheol Moon, Sungyu Yang, Kyeong Suk Han, Goya Choi and A Yeong Lee

Molecules 2016, 21(3), 270; https://doi.org/10.3390/molecules21030270 - 29 Feb 2016

Cited by 39 | Viewed by 6366

Abstract

Accurate identification of the plant species that are present in herbal medicines is important for quality control. Although the dried roots of Aralia continentalis (Araliae Continentalis Radix) and Angelica biserrata (Angelicae Pubescentis Radix) are used in the same traditional medicine, namely Dok-Hwal in [...] Read more.

Accurate identification of the plant species that are present in herbal medicines is important for quality control. Although the dried roots of Aralia continentalis (Araliae Continentalis Radix) and Angelica biserrata (Angelicae Pubescentis Radix) are used in the same traditional medicine, namely Dok-Hwal in Korean and Du-Huo in Chinese, the medicines are described differently in the national pharmacopeia. Further confusion arises from the distribution of dried Levisticum officinale and Heracleum moellendorffii roots as the same medicine. Medicinal ingredients from all four plants are morphologically similar, and discrimination is difficult using conventional methods. Molecular identification methods offer rapidity and accuracy. The internal transcribed spacer 2 (ITS2) region of the nuclear ribosomal RNA gene (rDNA) was sequenced in all four plant species, and the sequences were used to design species-specific primers. Primers for each species were then combined to allow sample analysis in a single PCR reaction. Commercial herbal medicine samples were obtained from Korea and China and analyzed using the multiplex assay. The assay successfully identified authentic medicines and also identified inauthentic or adulterated samples. The multiplex assay will be a useful tool for identification of authentic Araliae Continentalis Radix and/or Angelicae Pubescentis Radix preparations in Korea and China. Full article

(This article belongs to the Section Natural Products Chemistry)

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13 pages, 552 KiB

Open AccessArticle

Biological Validation of Novel Polysubstituted Pyrazole Candidates with in Vitro Anticancer Activities

by Hoda H. Fahmy, Nagy M. Khalifa, Magda M. F. Ismail, Hend M. El-Sahrawy and Eman S. Nossier

Molecules 2016, 21(3), 271; https://doi.org/10.3390/molecules21030271 - 26 Feb 2016

Cited by 55 | Viewed by 4697

Abstract

With the aim of developing novel antitumor scaffolds, a novel series of polysubstituted pyrazole derivatives linked to different nitrogenous heterocyclic ring systems at the C-4 position were synthesized through different chemical reactions and characterized by means of spectral and elemental analyses and their [...] Read more.

With the aim of developing novel antitumor scaffolds, a novel series of polysubstituted pyrazole derivatives linked to different nitrogenous heterocyclic ring systems at the C-4 position were synthesized through different chemical reactions and characterized by means of spectral and elemental analyses and their antiproliferative activity against 60 different human tumor cell lines was validated by the U.S. National Cancer Institute using a two stage process. The in vitro anticancer evaluation revealed that compound 9 showed increased potency toward most human tumor cell lines with GI₅₀MG-MID = 3.59 µM, as compared to the standard drug sorafenib (GI₅₀ MG-MID = 1.90 µM). At the same time, compounds 6a and 7 were selective against the HOP-92 cell line of non-small cell lung cancer with GI₅₀ 1.65 and 1.61 µM, respectively. Full article

(This article belongs to the Section Bioorganic Chemistry)

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14 pages, 1632 KiB

Open AccessReview

Application of Ionic Liquids in Pot-in-Pot Reactions

by Simge Çınar, Michael D. Schulz, Stephanie Oyola-Reynoso, David K. Bwambok, Symon M. Gathiaka and Martin Thuo

Molecules 2016, 21(3), 272; https://doi.org/10.3390/molecules21030272 - 26 Feb 2016

Cited by 5 | Viewed by 8095

Abstract

Pot-in-pot reactions are designed such that two reaction media (solvents, catalysts and reagents) are isolated from each other by a polymeric membrane similar to matryoshka dolls (Russian nesting dolls). The first reaction is allowed to progress to completion before triggering the second reaction [...] Read more.

Pot-in-pot reactions are designed such that two reaction media (solvents, catalysts and reagents) are isolated from each other by a polymeric membrane similar to matryoshka dolls (Russian nesting dolls). The first reaction is allowed to progress to completion before triggering the second reaction in which all necessary solvents, reactants, or catalysts are placed except for the starting reagent for the target reaction. With the appropriate trigger, in most cases unidirectional flux, the product of the first reaction is introduced to the second medium allowing a second transformation in the same glass reaction pot—albeit separated by a polymeric membrane. The basis of these reaction systems is the controlled selective flux of one reagent over the other components of the first reaction while maintaining steady-state catalyst concentration in the first “pot”. The use of ionic liquids as tools to control chemical potential across the polymeric membranes making the first pot is discussed based on standard diffusion models—Fickian and Payne’s models. Besides chemical potential, use of ionic liquids as delivery agent for a small amount of a solvent that slightly swells the polymeric membrane, hence increasing flux, is highlighted. This review highlights the critical role ionic liquids play in site-isolation of multiple catalyzed reactions in a standard pot-in-pot reaction. Full article

(This article belongs to the Special Issue Ionic Liquids in Organic Synthesis)

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9 pages, 1178 KiB

Open AccessArticle

Structure Determination of Novel Oxidation Products from Epicatechin: Thearubigin-Like Molecules

by Kazuhiro Uchida, Kazuki Ogawa and Emiko Yanase

Molecules 2016, 21(3), 273; https://doi.org/10.3390/molecules21030273 - 26 Feb 2016

Cited by 18 | Viewed by 7074

Abstract

Following the oxidation of epicatechin (EC), three novel compounds and two known compounds were isolated. The chemical structures of these oxidation products were determined by mass spectrometry (MS) and various nuclear magnetic resonance (NMR) experiments, and the A-ring–B-ring linkage that is characteristic of [...] Read more.

Following the oxidation of epicatechin (EC), three novel compounds and two known compounds were isolated. The chemical structures of these oxidation products were determined by mass spectrometry (MS) and various nuclear magnetic resonance (NMR) experiments, and the A-ring–B-ring linkage that is characteristic of catechin was found in each molecule. Three compounds showed similar ultraviolet–visible (UV-Vis) spectra to EC, whereas two compounds showed different spectral absorption in the region between 300 and 500 nm. A similar spectrum was obtained for the thearubigin fraction prepared from a black tea infusion. This result suggests that the condensation reaction between the A-ring and B-ring is more important than reaction between B-rings for thearubigin formation. Full article

(This article belongs to the Section Natural Products Chemistry)

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8 pages, 988 KiB

Open AccessArticle

Sesquiterpenoids from Chinese Agarwood Induced by Artificial Holing

by Wei Li, Ge Liao, Wen-Hua Dong, Fan-Dong Kong, Pei Wang, Hao Wang, Wen-Li Mei and Hao-Fu Dai

Molecules 2016, 21(3), 274; https://doi.org/10.3390/molecules21030274 - 26 Feb 2016

Cited by 40 | Viewed by 6226

Abstract

Two new sesquiterpenoids, 3-oxo-7-hydroxylholosericin A (1) and 1,5;8,12-diepoxy-guaia-12-one (2), together with seven known sesquiterpenoids 3–9, were isolated from Chinese agarwood induced by artificial holing originating from Aquilaria sinensis (Lour.) Gilg. Their structures were identified by spectroscopic techniques (UV, IR, 1D and 2D NMR) [...] Read more.

Two new sesquiterpenoids, 3-oxo-7-hydroxylholosericin A (1) and 1,5;8,12-diepoxy-guaia-12-one (2), together with seven known sesquiterpenoids 3–9, were isolated from Chinese agarwood induced by artificial holing originating from Aquilaria sinensis (Lour.) Gilg. Their structures were identified by spectroscopic techniques (UV, IR, 1D and 2D NMR) and MS analyses. The absolute configuration of compound 1 was determined by comparison of its measured CD curve with that of calculated data for 1 and ent-1. The NMR data of 3 were reported in this study for the first time. Compounds 1, 2, 4–6, together with the EtOAc extract showed moderate inhibitory activities against acetylcholinesterase, and compounds 4–6, 8 exhibited antibacterial activities against Staphylococcus aureus or Ralstonia solanacearum. Full article

(This article belongs to the Collection Bioactive Compounds)

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14 pages, 994 KiB

Open AccessArticle

Quantitative Variation of Flavonoids and Diterpenes in Leaves and Stems of Cistus ladanifer L. at Different Ages

by Cristina Valares Masa, Teresa Sosa Díaz, Juan Carlos Alías Gallego and Natividad Chaves Lobón

Molecules 2016, 21(3), 275; https://doi.org/10.3390/molecules21030275 - 27 Feb 2016

Cited by 30 | Viewed by 6867

Abstract

The compounds derived from secondary metabolism in plants perform a variety of ecological functions, providing the plant with resistance to biotic and abiotic factors. The basal levels of these metabolites for each organ, tissue or cell type depend on the development stage of [...] Read more.

The compounds derived from secondary metabolism in plants perform a variety of ecological functions, providing the plant with resistance to biotic and abiotic factors. The basal levels of these metabolites for each organ, tissue or cell type depend on the development stage of the plant and they may be modified as a response to biotic and/or abiotic stress. As a consequence, the resistance state of a plant may vary in space and time. The secondary metabolites of Cistus ladanifer have been quantified in leaves and stems throughout autumn, winter, spring and summer, and at different ages of the plant. This study shows that there are significant differences between young leaves, mature leaves and stems, and between individuals of different ages. Young leaves show significantly greater synthesis of flavonoids and diterpenes than mature leaves and stems, with a clear seasonal variation, and the differences between leaves at different growth stages and stems is maintained during the quantified seasons. With respect to age, specimens under one year of age secreted significantly lower amounts of compounds. The variation in the composition of secondary metabolites between different parts of the plant, the season and the variations in age may determine the interactions of Cistus ladanifer with the biotic and abiotic factors to which it is exposed. Full article

(This article belongs to the Collection Phytochemicals: Biosynthesis, Metabolism and Biological Activities)

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12 pages, 596 KiB

Open AccessArticle

Synthesis and Bioactivities of Novel Pyrazole Oxime Derivatives Containing a 5-Trifluoromethylpyridyl Moiety

by Hong Dai, Jia Chen, Hong Li, Baojiang Dai, Haibing He, Yuan Fang and Yujun Shi

Molecules 2016, 21(3), 276; https://doi.org/10.3390/molecules21030276 - 27 Feb 2016

Cited by 30 | Viewed by 7112

Abstract

In this study, in order to find novel biologically active pyrazole oxime compounds, a series of pyrazole oxime derivatives containing a 5-trifluoromethylpyridyl moiety were synthesized. Preliminary bioassays indicated that most title compounds were found to display good to excellent acaricidal activity against Tetranychus [...] Read more.

In this study, in order to find novel biologically active pyrazole oxime compounds, a series of pyrazole oxime derivatives containing a 5-trifluoromethylpyridyl moiety were synthesized. Preliminary bioassays indicated that most title compounds were found to display good to excellent acaricidal activity against Tetranychus cinnabarinus at a concentration of 200 μg/mL, and some designed compounds still showed excellent acaricidal activity against Tetranychus cinnabarinus at the concentration of 10 μg/mL, especially since the inhibition rates of compounds 8e, 8f, 8l, 8m, 8n, 8p, and 8q were all 100.00%. Interestingly, some target compounds exhibited moderate to good insecticidal activities against Plutella xylostella and Aphis craccivora at a concentration of 200 μg/mL; furthermore, compounds 8e and 8l possessed outstanding insecticidal activities against Plutella xylostella under the concentration of 50 μg/mL. Full article

(This article belongs to the Section Organic Chemistry)

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10 pages, 1354 KiB

Open AccessArticle

Antidepressant-Like Effects of Lindera obtusiloba Extracts on the Immobility Behavior of Rats in the Forced Swim Test

by Dong Wook Lim, Mi-Sook Lee, Song Her, Suengmok Cho, Chang-Ho Lee, In-Ho Kim and Daeseok Han

Molecules 2016, 21(3), 277; https://doi.org/10.3390/molecules21030277 - 27 Feb 2016

Cited by 7 | Viewed by 5977

Abstract

Lindera obtusiloba extracts are commonly used as an alternative medicine due to its numerous health benefits in Korea. However, the antidepressant-like effects of L. obtusiloba extracts have not been fully elucidated. In this study, we aimed to determine whether L. obtusiloba extracts exhibited [...] Read more.

Lindera obtusiloba extracts are commonly used as an alternative medicine due to its numerous health benefits in Korea. However, the antidepressant-like effects of L. obtusiloba extracts have not been fully elucidated. In this study, we aimed to determine whether L. obtusiloba extracts exhibited antidepressant-like activity in rats subjected to forced swim test (FST)-induced depression. Acute treatment of rats with L. obtusiloba extracts (200 mg/kg, p.o.) significantly reduced immobility time and increased swimming time without any significant change in climbing. Rats treated with L. obtusiloba extracts also exhibited a decrease in the limbic hypothalamic-pituitary-adrenal (HPA) axis response to the FST, as indicated by attenuation of the corticosterone response and decreased c-Fos immunoreactivity in the hippocampus CA3 region. In addition, L. obtusiloba extracts, at concentrations that were not affected by cell viability, significantly decreased luciferase activity in response to cortisol in a concentration-dependent manner by the glucocorticoid binding assay in HeLa cells. Our findings suggested that the antidepressant-like effects of L. obtusiloba extracts were likely mediated via the glucocorticoid receptor (GR). Further studies are needed to evaluate the potential of L. obtusiloba extracts as an alternative therapeutic approach for the treatment of depression. Full article

(This article belongs to the Section Natural Products Chemistry)

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6 pages, 412 KiB

Open AccessArticle

Rhodium Porphyrin Bound to a Merrifield Resin as Heterogeneous Catalyst for the Cyclopropanation Reaction of Olefins

by Alina Ciammaichella, Valeria Cardoni, Alessandro Leoni and Pietro Tagliatesta

Molecules 2016, 21(3), 278; https://doi.org/10.3390/molecules21030278 - 27 Feb 2016

Cited by 7 | Viewed by 5147

Abstract

Cyclopropanation reaction is an important tool for obtaining interesting compounds and can be catalyzed by metalloporphyrins with high syn/anti ratio. The catalyst cannot be recycled and is usually lost during chromatographic separation from the two isomeric products. In this paper a meso-tetraphenylporphyrin [...] Read more.

Cyclopropanation reaction is an important tool for obtaining interesting compounds and can be catalyzed by metalloporphyrins with high syn/anti ratio. The catalyst cannot be recycled and is usually lost during chromatographic separation from the two isomeric products. In this paper a meso-tetraphenylporphyrin rhodium(III) chloride was bound to a Merrifield resin and used to catalyze the cyclopropanation reaction of nine olefins, giving good yields and selectivities of the final products and for the first time, a partial recycling of the catalyst. This new catalytic system will be tested in the future for the synthesis of natural products containing cyclopropyl ring. Full article

(This article belongs to the Special Issue Tetrapyrrolic Macrocycles: Synthesis, Functionalization and Applications)

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12 pages, 5950 KiB

Open AccessArticle

1-Deoxynojirimycin Alleviates Liver Injury and Improves Hepatic Glucose Metabolism in db/db Mice

by Qingpu Liu, Xuan Li, Cunyu Li, Yunfeng Zheng, Fang Wang, Hongyang Li and Guoping Peng

Molecules 2016, 21(3), 279; https://doi.org/10.3390/molecules21030279 - 27 Feb 2016

Cited by 57 | Viewed by 7606

Abstract

The present study investigated the effect of 1-Deoxynojirimycin (DNJ) on liver injury and hepatic glucose metabolism in db/db mice. Mice were divided into five groups: normal control, db/db control, DNJ-20 (DNJ 20 mg·kg⁻¹·day⁻¹), DNJ-40 (DNJ [...] Read more.

The present study investigated the effect of 1-Deoxynojirimycin (DNJ) on liver injury and hepatic glucose metabolism in db/db mice. Mice were divided into five groups: normal control, db/db control, DNJ-20 (DNJ 20 mg·kg⁻¹·day⁻¹), DNJ-40 (DNJ 40 mg·kg⁻¹·day⁻¹) and DNJ-80 (DNJ 80 mg·kg⁻¹·day⁻¹). All doses were treated intravenously by tail vein for four weeks. DNJ was observed to significantly reduce the levels of serum triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) and liver TG, as well as activities of serum alanine aminotransferase (ALT), and aspartate transaminase (AST); DNJ also alleviated macrovesicular steatosis and decreased tumor necrosis factor α (TNF-α), interleukin-1 (IL-1), interleukin-6 (IL-6) levels in liver tissue. Furthermore, DNJ treatment significantly increased hepatic glycogen content, the activities of hexokinase (HK), pyruvate kinase (PK) in liver tissue, and decreased the activities of glucose-6-phosphatase (G6Pase), glycogen phosphorylase (GP), and phosphoenolpyruvate carboxykinase (PEPCK). Moreover, DNJ increased the phosphorylation of phosphatidylinositol 3 kinase (PI3K) on p85, protein kinase B (PKB) on Ser473, glycogen synthase kinase 3β (GSK-3β) on Ser9, and inhibited phosphorylation of glycogen synthase (GS) on Ser645 in liver tissue of db/db mice. These results demonstrate that DNJ can increase hepatic insulin sensitivity via strengthening of the insulin-stimulated PKB/GSK-3β signal pathway and by modulating glucose metabolic enzymes in db/db mice. Moreover, DNJ also can improve lipid homeostasis and attenuate hepatic steatosis in db/db mice. Full article

(This article belongs to the Section Medicinal Chemistry)

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13 pages, 873 KiB

Open AccessReview

Targeting Reactive Carbonyl Species with Natural Sequestering Agents

by Sung Won Hwang, Yoon-Mi Lee, Giancarlo Aldini and Kyung-Jin Yeum

Molecules 2016, 21(3), 280; https://doi.org/10.3390/molecules21030280 - 27 Feb 2016

Cited by 28 | Viewed by 7295

Abstract

Reactive carbonyl species generated by the oxidation of polyunsaturated fatty acids and sugars are highly reactive due to their electrophilic nature, and are able to easily react with the nucleophilic sites of proteins as well as DNA causing cellular dysfunction. Levels of reactive [...] Read more.

Reactive carbonyl species generated by the oxidation of polyunsaturated fatty acids and sugars are highly reactive due to their electrophilic nature, and are able to easily react with the nucleophilic sites of proteins as well as DNA causing cellular dysfunction. Levels of reactive carbonyl species and their reaction products have been reported to be elevated in various chronic diseases, including metabolic disorders and neurodegenerative diseases. In an effort to identify sequestering agents for reactive carbonyl species, various analytical techniques such as spectrophotometry, high performance liquid chromatography, western blot, and mass spectrometry have been utilized. In particular, recent advances using a novel high resolution mass spectrometry approach allows screening of complex mixtures such as natural products for their sequestering ability of reactive carbonyl species. To overcome the limited bioavailability and bioefficacy of natural products, new techniques using nanoparticles and nanocarriers may offer a new attractive strategy for increased in vivo utilization and targeted delivery of bioactives. Full article

(This article belongs to the Special Issue 20th Anniversary of Molecules—Recent Advances in Natural Products)

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8 pages, 1037 KiB

Open AccessArticle

Three New Sesquiterpenoids and One New Sesquiterpenoid Derivative from Chinese Eaglewood

by Huan Zhao, Qinghua Peng, Zhuzhen Han, Li Yang and Zhengtao Wang

Molecules 2016, 21(3), 281; https://doi.org/10.3390/molecules21030281 - 27 Feb 2016

Cited by 23 | Viewed by 5596

Abstract

Three new sesquiterpenoids (1–3) and one new sesquiterpenoid derivative (4), along with three known sesquiterpenoids (5–7), were isolated from the 95% ethanolic extract of Chinese eaglewood [Aquilaria sinensis (Lour.) Gilg]. The structures [...] Read more.

Three new sesquiterpenoids (1–3) and one new sesquiterpenoid derivative (4), along with three known sesquiterpenoids (5–7), were isolated from the 95% ethanolic extract of Chinese eaglewood [Aquilaria sinensis (Lour.) Gilg]. The structures of these compounds were elucidated through extensive analysis of spectroscopic data including IR, NMR, HRESIMS, and X-ray diffraction experiments. In addition, the above new compounds were detected for their bioactivities against LPS-induced NO production in RAW 264.7 cells. Among them, compound 2 exhibited obvious anti-inflammatory activity with an IC₅₀ value of 8.1 μM. Full article

(This article belongs to the Section Natural Products Chemistry)

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14 pages, 6825 KiB

Open AccessArticle

Self-Assembled Modified Soy Protein/Dextran Nanogel Induced by Ultrasonication as a Delivery Vehicle for Riboflavin

by Bei Jin, Xiaosong Zhou, Xiangzhong Li, Weiqin Lin, Guangbin Chen and Riji Qiu

Molecules 2016, 21(3), 282; https://doi.org/10.3390/molecules21030282 - 15 Mar 2016

Cited by 61 | Viewed by 8247

Abstract

A simple and green approach was developed to produce a novel nanogel via self-assembly of modified soy protein and dextran, to efficiently deliver riboflavin. First, modified soy protein was prepared by heating denaturation at 60 °C for 30 min or Alcalase hydrolysis for [...] Read more.

A simple and green approach was developed to produce a novel nanogel via self-assembly of modified soy protein and dextran, to efficiently deliver riboflavin. First, modified soy protein was prepared by heating denaturation at 60 °C for 30 min or Alcalase hydrolysis for 40 min. Second, modified soy protein was mixed with dextran and ultrasonicated for 70 min so as to assemble nanogels. The modified soy protein-dextran nanogels were characterized by Fourier-transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) and ζ-potential studies to confirm the formation of NGs. Transmission electron microscopy (TEM) revealed the NGs to be spherical with core-shell structures, in the range of 32–40 nm size. The nanogels were stable against various environmental conditions. Furthermore, the particle size of the nanogels hardly changed with the incorporation of riboflavin. The encapsulation efficiency of nanogels was found to be up to 65.9% at a riboflavin concentration of 250 μg/mL. The nanogels exhibited a faster release in simulated intestine fluid (SIF) compared with simulated gastric fluid (SGF). From the results obtained it can be concluded that modified soy protein-dextran nanogels can be considered a promising carrier for drugs and other bioactive molecule delivery purposes. Full article

(This article belongs to the Special Issue Pharmaceutical Nanotechnology: Novel Approaches)

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10 pages, 2832 KiB

Open AccessArticle

Methanolic Extract of Pien Tze Huang Induces Apoptosis Signaling in Human Osteosarcoma MG63 Cells via Multiple Pathways

by Yong Fu, Li Zhang, Zhenqiang Hong, Haiyin Zheng, Nan Li, Hongjian Gao, Boyi Chen and Yi Zhao

Molecules 2016, 21(3), 283; https://doi.org/10.3390/molecules21030283 - 1 Mar 2016

Cited by 17 | Viewed by 6309

Abstract

Pien Tze Huang (PZH) is a well-known traditional Chinese formulation and has long been used as an alternative remedy for cancers in China and Southeast Asia. Recently, antitumor activity of PZH on several tumors have been increasingly reported, but its antitumor activity and [...] Read more.

Pien Tze Huang (PZH) is a well-known traditional Chinese formulation and has long been used as an alternative remedy for cancers in China and Southeast Asia. Recently, antitumor activity of PZH on several tumors have been increasingly reported, but its antitumor activity and the possible action mechanism on osteosarcoma remains unclear. After treatment with PZH, cell viability of MG-63 cells was dose-dependently inhibited compared to control cells. Moreover, a DNA ladder characteristic of apoptosis was observed in the cells treated with PZH, especially 500 μg/mL, 750 μg/mL. Further investigation showed that PZH treatments led to activation of caspase cascades and changes of apoptotic mediators Bcl2, Bax, and Bcl-xL expression. In addition, our results suggested that PZH activated PI3K/Akt signal pathway, and the phosphorylation of Akt and ERK1/2 were associated with the induction of apoptotic signaling. These results revealed that PZH possesses antitumoral activity on human osteosarcoma MG63 cells by manipulating apoptotic signaling and multiple pathways. It is suggested that PZH alone or combined with regular antitumor drugs may be beneficial as osteosarcoma treatments. Full article

(This article belongs to the Section Medicinal Chemistry)

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18 pages, 730 KiB

Open AccessReview

New Approaches to the Role of Thrombin in Acute Coronary Syndromes: Quo Vadis Bivalirudin, a Direct Thrombin Inhibitor?

by María Asunción Esteve-Pastor, Diana Hernández-Romero, Mariano Valdés and Francisco Marín

Molecules 2016, 21(3), 284; https://doi.org/10.3390/molecules21030284 - 27 Feb 2016

Cited by 2 | Viewed by 11558

Abstract

The pathophysiology of acute coronary syndrome (ACS) involves platelet activation and thrombus formation after the rupture of atherosclerotic plaques. Thrombin is generated at the blood-plaque interface in association with cellular membranes on cells and platelets. Thrombin also amplifies the response to the tissue [...] Read more.

The pathophysiology of acute coronary syndrome (ACS) involves platelet activation and thrombus formation after the rupture of atherosclerotic plaques. Thrombin is generated at the blood-plaque interface in association with cellular membranes on cells and platelets. Thrombin also amplifies the response to the tissue injury, coagulation and platelet response, so the treatment of ACS is based on the combined use of both antiplatelet (such as aspirin, clopidogrel, prasugrel and ticagrelor) and antithrombotic drugs (unfractionated heparin, enoxaparin, fondaparinux and bivalirudin). Bivalirudin competitively inhibits thrombin with high affinity, a predictable response from its linear pharmacokinetics and short action. However, a present remarkable controversy exists between the latest main Guidelines in Clinical Practice and the key trials evaluating the use of bivalirudin in ACS. The aim of this review is to update the development of bivalirudin, including pharmacological properties, obtained information from clinical trials evaluating efficacy and safety of bivalirudin in ACS; as well as the recommendations of clinical Guidelines. Full article

(This article belongs to the Special Issue Thrombin Inhibitors: Discovery and Design)

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26 pages, 1515 KiB

Open AccessReview

Biofuels and Their Co-Products as Livestock Feed: Global Economic and Environmental Implications

by József Popp, Mónika Harangi-Rákos, Zoltán Gabnai, Péter Balogh, Gabriella Antal and Attila Bai

Molecules 2016, 21(3), 285; https://doi.org/10.3390/molecules21030285 - 29 Feb 2016

Cited by 98 | Viewed by 11707 | Correction

Abstract

This review studies biofuel expansion in terms of competition between conventional and advanced biofuels based on bioenergy potential. Production of advanced biofuels is generally more expensive than current biofuels because products are not yet cost competitive. What is overlooked in the discussion about [...] Read more.

This review studies biofuel expansion in terms of competition between conventional and advanced biofuels based on bioenergy potential. Production of advanced biofuels is generally more expensive than current biofuels because products are not yet cost competitive. What is overlooked in the discussion about biofuel is the contribution the industry makes to the global animal feed supply and land use for cultivation of feedstocks. The global ethanol industry produces 44 million metric tonnes of high-quality feed, however, the co-products of biodiesel production have a moderate impact on the feed market contributing to just 8–9 million tonnes of protein meal output a year. By economically displacing traditional feed ingredients co-products from biofuel production are an important and valuable component of the biofuels sector and the global feed market. The return of co-products to the feed market has agricultural land use (and GHG emissions) implications as well. The use of co-products generated from grains and oilseeds can reduce net land use by 11% to 40%. The proportion of global cropland used for biofuels is currently some 2% (30–35 million hectares). By adding co-products substituted for grains and oilseeds the land required for cultivation of feedstocks declines to 1.5% of the global crop area. Full article

(This article belongs to the Special Issue Enabling Technologies and Green Processes for Biorefinery Strategies and Biomass Valorization)

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13 pages, 438 KiB

Open AccessCommunication

On the Traceability of Commercial Saffron Samples Using ¹H-NMR and FT-IR Metabolomics

by Roberto Consonni, Stella A. Ordoudi, Laura R. Cagliani, Maria Tsiangali and Maria Z. Tsimidou

Molecules 2016, 21(3), 286; https://doi.org/10.3390/molecules21030286 - 29 Feb 2016

Cited by 41 | Viewed by 6293

Abstract

In previous works on authentic samples of saffron of known history (harvest and processing year, storage conditions, and length of time) some biomarkers were proposed using both FT-IR and NMR metabolomics regarding the shelf life of the product. This work addresses the difficulties [...] Read more.

In previous works on authentic samples of saffron of known history (harvest and processing year, storage conditions, and length of time) some biomarkers were proposed using both FT-IR and NMR metabolomics regarding the shelf life of the product. This work addresses the difficulties to trace back the “age” of commercial saffron samples of unknown history, sets a limit value above which these products can be considered substandard, and offers a useful tool to combat saffron mislabeling and fraud with low-quality saffron material. Investigations of authentic and commercial saffron samples of different origin and harvest year, which had been stored under controlled conditions for different lengths of time, allowed a clear-cut clustering of samples in two groups according to the storage period irrespectively of the provenience. In this respect, the four-year cut off point proposed in our previous work assisted to trace back the “age” of unknown samples and to check for possible mislabeling practices. Full article

(This article belongs to the Special Issue Saffron (Crocus sativus, L.): Omics and Other Techniques in Authenticity, Quality and Bioactivity Studies)

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9 pages, 1535 KiB

Open AccessArticle

Incorporation of Amino Acids with Long-Chain Terminal Olefins into Proteins

by Matthias P. Exner, Sebastian Köhling, Julie Rivollier, Sandrine Gosling, Puneet Srivastava, Zheni I. Palyancheva, Piet Herdewijn, Marie-Pierre Heck, Jörg Rademann and Nediljko Budisa

Molecules 2016, 21(3), 287; https://doi.org/10.3390/molecules21030287 - 29 Feb 2016

Cited by 10 | Viewed by 8148

Abstract

The increasing need for site-specific protein decorations that mimic natural posttranslational modifications requires access to a variety of noncanonical amino acids with moieties enabling bioorthogonal conjugation chemistry. Here we present the incorporation of long-chain olefinic amino acids into model proteins with rational variants [...] Read more.

The increasing need for site-specific protein decorations that mimic natural posttranslational modifications requires access to a variety of noncanonical amino acids with moieties enabling bioorthogonal conjugation chemistry. Here we present the incorporation of long-chain olefinic amino acids into model proteins with rational variants of pyrrolysyl-tRNA synthetase (PylRS). N_ε-heptenoyl lysine was incorporated for the first time using the known promiscuous variant PylRS(Y306A/Y384F), and N_ε-pentenoyl lysine was incorporated in significant yields with the novel variant PylRS(C348A/Y384F). This is the only example of rational modification at position C348 to enlarge the enzyme’s binding pocket. Furthermore, we demonstrate the feasibility of our chosen amino acids in the thiol-ene conjugation reaction with a thiolated polysaccharide. Full article

(This article belongs to the Special Issue Biomolecules Modification)

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12 pages, 1824 KiB

Open AccessArticle

Can Expanded Bacteriochlorins Act as Photosensitizers in Photodynamic Therapy? Good News from Density Functional Theory Computations

by Gloria Mazzone, Marta E. Alberto, Bruna C. De Simone, Tiziana Marino and Nino Russo

Molecules 2016, 21(3), 288; https://doi.org/10.3390/molecules21030288 - 29 Feb 2016

Cited by 41 | Viewed by 6145

Abstract

The main photophysical properties of a series of expanded bacteriochlorins, recently synthetized, have been investigated by means of DFT and TD-DFT methods. Absorption spectra computed with different exchange-correlation functionals, B3LYP, M06 and ωB97XD, have been compared with the experimental ones. In good agreement, [...] Read more.

The main photophysical properties of a series of expanded bacteriochlorins, recently synthetized, have been investigated by means of DFT and TD-DFT methods. Absorption spectra computed with different exchange-correlation functionals, B3LYP, M06 and ωB97XD, have been compared with the experimental ones. In good agreement, all the considered systems show a maximum absorption wavelength that falls in the therapeutic window (600–800 nm). The obtained singlet-triplet energy gaps are large enough to ensure the production of cytotoxic singlet molecular oxygen. The computed spin-orbit matrix elements suggest a good probability of intersystem spin-crossing between singlet and triplet excited states, since they result to be higher than those computed for 5,10,15,20-tetrakis-(m-hydroxyphenyl)chlorin (Foscan©) already used in the photodynamic therapy (PDT) protocol. Because of the investigated properties, these expanded bacteriochlorins can be proposed as PDT agents. Full article

(This article belongs to the Special Issue Tetrapyrrolic Macrocycles: Synthesis, Functionalization and Applications)

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13 pages, 4022 KiB

Open AccessArticle

Photochemistry of the α-Al₂O₃-PETN Interface

by Roman V. Tsyshevsky, Anton Zverev, Anatoly Mitrofanov, Sergey N. Rashkeev and Maija M. Kuklja

Molecules 2016, 21(3), 289; https://doi.org/10.3390/molecules21030289 - 29 Feb 2016

Cited by 10 | Viewed by 8631

Abstract

Optical absorption measurements are combined with electronic structure calculations to explore photochemistry of an α-Al₂O₃-PETN interface formed by a nitroester (pentaerythritol tetranitrate, PETN, C₅H₈N₄O₁₂) and a wide band gap aluminum oxide [...] Read more.

Optical absorption measurements are combined with electronic structure calculations to explore photochemistry of an α-Al₂O₃-PETN interface formed by a nitroester (pentaerythritol tetranitrate, PETN, C₅H₈N₄O₁₂) and a wide band gap aluminum oxide (α-Al₂O₃) substrate. The first principles modeling is used to deconstruct and interpret the α-Al₂O₃-PETN absorption spectrum that has distinct peaks attributed to surface F⁰-centers and surface—PETN transitions. We predict the low energy α-Al₂O₃ F⁰-center—PETN transition, producing the excited triplet state, and α-Al₂O₃ F⁰-center—PETN charge transfer, generating the PETN anion radical. This implies that irradiation by commonly used lasers can easily initiate photodecomposition of both excited and charged PETN at the interface. The feasible mechanism of the photodecomposition is proposed. Full article

(This article belongs to the Special Issue Photoactive Molecules)

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14 pages, 2866 KiB

Open AccessArticle

The Role of CD44 and ERM Proteins in Expression and Functionality of P-glycoprotein in Breast Cancer Cells

by Deep Pokharel, Matthew P. Padula, Jamie F. Lu, Ritu Jaiswal, Steven P. Djordjevic and Mary Bebawy

Molecules 2016, 21(3), 290; https://doi.org/10.3390/molecules21030290 - 1 Mar 2016

Cited by 48 | Viewed by 8012

Abstract

Multidrug resistance (MDR) is often attributed to the over-expression of P-glycoprotein (P-gp), which prevents the accumulation of anticancer drugs within cells by virtue of its active drug efflux capacity. We have previously described the intercellular transfer of P-gp via extracellular vesicles (EVs) and [...] Read more.

Multidrug resistance (MDR) is often attributed to the over-expression of P-glycoprotein (P-gp), which prevents the accumulation of anticancer drugs within cells by virtue of its active drug efflux capacity. We have previously described the intercellular transfer of P-gp via extracellular vesicles (EVs) and proposed the involvement of a unique protein complex in regulating this process. In this paper, we investigate the role of these mediators in the regulation of P-gp functionality and hence the acquisition of MDR following cell to cell transfer. By sequentially silencing the FERM domain-binding proteins, Ezrin, Radixin and Moesin (ERM), as well as CD44, which we also report a selective packaging in breast cancer derived EVs, we have established a role for these proteins, in particular Radixin and CD44, in influencing the P-gp-mediated MDR in whole cells. We also report for the first time the role of ERM proteins in the vesicular transfer of functional P-gp. Specifically, we demonstrate that intercellular membrane insertion is dependent on Ezrin and Moesin, whilst P-gp functionality is governed by the integrity of all ERM proteins in the recipient cell. This study identifies these candidate proteins as potential new therapeutic targets in circumventing MDR clinically. Full article

(This article belongs to the Special Issue New Approaches to Counteract Drug Resistance in Cancer)

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25 pages, 3531 KiB

Open AccessReview

Recent Advances in Solid Catalysts Obtained by Metalloporphyrins Immobilization on Layered Anionic Exchangers: A Short Review and Some New Catalytic Results

by Shirley Nakagaki, Karen Mary Mantovani, Guilherme Sippel Machado, Kelly Aparecida Dias de Freitas Castro and Fernando Wypych

Molecules 2016, 21(3), 291; https://doi.org/10.3390/molecules21030291 - 29 Feb 2016

Cited by 53 | Viewed by 8827

Abstract

Layered materials are a very interesting class of compounds obtained by stacking of two-dimensional layers along the basal axis. A remarkable property of these materials is their capacity to interact with a variety of chemical species, irrespective of their charge (neutral, cationic or [...] Read more.

Layered materials are a very interesting class of compounds obtained by stacking of two-dimensional layers along the basal axis. A remarkable property of these materials is their capacity to interact with a variety of chemical species, irrespective of their charge (neutral, cationic or anionic). These species can be grafted onto the surface of the layered materials or intercalated between the layers, to expand or contract the interlayer distance. Metalloporphyrins, which are typically soluble oxidation catalysts, are examples of molecules that can interact with layered materials. This work presents a short review of the studies involving metalloporphyrin immobilization on two different anionic exchangers, Layered Double Hydroxides (LDHs) and Layered Hydroxide Salts (LHSs), published over the past year. After immobilization of anionic porphyrins, the resulting solids behave as reusable catalysts for heterogeneous oxidation processes. Although a large number of publications involving metalloporphyrin immobilization on LDHs exist, only a few papers have dealt with LHSs as supports, so metalloporphyrins immobilized on LHSs represent a new and promising research field. This work also describes new results on an anionic manganese porphyrin (MnP) immobilized on Mg/Al-LDH solids with different nominal Mg/Al molar ratios (2:1, 3:1 and 4:1) and intercalated with different anions (CO₃²⁻ or NO₃⁻). The influence of the support composition on the MnP immobilization rates and the catalytic performance of the resulting solid in cyclooctene oxidation reactions will be reported. Full article

(This article belongs to the Special Issue Tetrapyrrolic Macrocycles: Synthesis, Functionalization and Applications)

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15 pages, 4599 KiB

Open AccessArticle

Modified Polyacrylic Acid-Zinc Composites: Synthesis, Characterization and Biological Activity

by Mohammed Rafi Shaik, Mufsir Kuniyil, Mujeeb Khan, Naushad Ahmad, Abdulrahman Al-Warthan, Mohammed Rafiq H. Siddiqui and Syed Farooq Adil

Molecules 2016, 21(3), 292; https://doi.org/10.3390/molecules21030292 - 29 Feb 2016

Cited by 21 | Viewed by 12996

Abstract

Polyacrylic acid (PAA) is an important industrial chemical, which has been extensively applied in various fields, including for several biomedical purposes. In this study, we report the synthesis and modification of this polymer with various phenol imides, such as succinimide, phthalimide and 1,8-naphthalimide. [...] Read more.

Polyacrylic acid (PAA) is an important industrial chemical, which has been extensively applied in various fields, including for several biomedical purposes. In this study, we report the synthesis and modification of this polymer with various phenol imides, such as succinimide, phthalimide and 1,8-naphthalimide. The as-synthesized derivatives were used to prepare polymer metal composites by the reaction with Zn⁺². These composites were characterized by using various techniques, including NMR, FT-IR, TGA, SEM and DSC. The as-prepared PAA-based composites were further evaluated for their anti-microbial properties against various pathogens, which include both Gram-positive and Gram-negative bacteria and different fungal strains. The synthesized composites have displayed considerable biocidal properties, ranging from mild to moderate activities against different strains tested. Full article

(This article belongs to the Section Bioorganic Chemistry)

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20 pages, 1228 KiB

Open AccessArticle

Large Scale Screening of Ethnomedicinal Plants for Identification of Potential Antibacterial Compounds

by Sujogya Kumar Panda, Yugal Kishore Mohanta, Laxmipriya Padhi, Young-Hwan Park, Tapan Kumar Mohanta and Hanhong Bae

Molecules 2016, 21(3), 293; https://doi.org/10.3390/molecules21030293 - 14 Mar 2016

Cited by 80 | Viewed by 12612

Abstract

The global burden of bacterial infections is very high and has been exacerbated by increasing resistance to multiple antibiotics. Antibiotic resistance leads to failed treatment of infections, which can ultimately lead to death. To overcome antibiotic resistance, it is necessary to identify new [...] Read more.

The global burden of bacterial infections is very high and has been exacerbated by increasing resistance to multiple antibiotics. Antibiotic resistance leads to failed treatment of infections, which can ultimately lead to death. To overcome antibiotic resistance, it is necessary to identify new antibacterial agents. In this study, a total of 662 plant extracts (diverse parts) from 222 plant species (82 families, 177 genera) were screened for antibacterial activity using the agar cup plate method. The aqueous and methanolic extracts were prepared from diverse plant parts and screened against eight bacterial (two Gram-positive and six Gram-negative) species, most of which are involved in common infections with multiple antibiotic resistance. The methanolic extracts of several plants were shown to have zones of inhibition ≥ 12 mm against both Gram-positive and Gram-negative bacteria. The minimum inhibitory concentration was calculated only with methanolic extracts of selected plants, those showed zone of inhibition ≥ 12 mm against both Gram-positive and Gram-negative bacteria. Several extracts had minimum inhibitory concentration ≤ 1 mg/mL. Specifically Adhatoda vasica, Ageratum conyzoides, Alangium salvifolium, Alpinia galanga, Andrographis paniculata, Anogeissus latifolia, Annona squamosa, A. reticulate, Azadirachta indica, Buchanania lanzan, Cassia fistula, Celastrus paniculatus, Centella asiatica, Clausena excavate, Cleome viscosa, Cleistanthus collinus, Clerodendrum indicum, Croton roxburghii, Diospyros melanoxylon, Eleutherine bulbosa, Erycibe paniculata, Eryngium foetidum, Garcinia cowa, Helicteres isora, Hemidesmus indicus, Holarrhena antidysenterica, Lannea coromandelica, Millettia extensa, Mimusops elengi, Nyctanthes arbor-tristis, Oroxylum indicum, Paederia foetida, Pterospermum acerifolium, Punica granatum, Semecarpus anacardium, Spondias pinnata, Terminalia alata and Vitex negundo were shown to have significant antimicrobial activity. The species listed here were shown to have anti-infective activity against both Gram-positive and Gram-negative bacteria. These results may serve as a guide for selecting plant species that could yield the highest probability of finding promising compounds responsible for the antibacterial activities against a broad spectrum of bacterial species. Further investigation of the phytochemicals from these plants will help to identify the lead compounds for drug discovery. Full article

(This article belongs to the Collection Antibiotics & Superbugs: New Strategies to Combat Antimicrobial Resistance)

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30 pages, 4628 KiB

Open AccessReview

Xanthones of Lichen Source: A 2016 Update

by Pierre Le Pogam and Joël Boustie

Molecules 2016, 21(3), 294; https://doi.org/10.3390/molecules21030294 - 2 Mar 2016

Cited by 46 | Viewed by 9945

Abstract

An update of xanthones encountered in lichens is proposed as more than 20 new xanthones have been described since the publication of the compendium of lichen metabolites by Huneck and Yoshimura in 1996. The last decades witnessed major advances regarding the elucidation of [...] Read more.

An update of xanthones encountered in lichens is proposed as more than 20 new xanthones have been described since the publication of the compendium of lichen metabolites by Huneck and Yoshimura in 1996. The last decades witnessed major advances regarding the elucidation of biosynthetic schemes leading to these fascinating compounds, accounting for the unique substitution patterns of a very vast majority of lichen xanthones. Besides a comprehensive analysis of the structures of xanthones described in lichens, their bioactivities and the emerging analytical strategies used to pinpoint them within lichens are presented here together with physico-chemical properties (including NMR data) as reported since 1996. Full article

(This article belongs to the Special Issue Coumarins, Xanthones and Related Compounds)

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11 pages, 14056 KiB

Open AccessArticle

Dendrobium moniliforme Exerts Inhibitory Effects on Both Receptor Activator of Nuclear Factor Kappa-B Ligand-Mediated Osteoclast Differentiation in Vitro and Lipopolysaccharide-Induced Bone Erosion in Vivo

by Jong Min Baek, Ju-Young Kim, Sung-Jun Ahn, Yoon-Hee Cheon, Miyoung Yang, Jaemin Oh and Min Kyu Choi

Molecules 2016, 21(3), 295; https://doi.org/10.3390/molecules21030295 - 1 Mar 2016

Cited by 19 | Viewed by 5801

Abstract

Dendrobium moniliforme (DM) is a well-known plant-derived extract that is widely used in Oriental medicine. DM and its chemical constituents have been reported to have a variety of pharmacological effects, including anti-oxidative, anti-inflammatory, and anti-tumor activities; however, no reports discuss the beneficial effects [...] Read more.

Dendrobium moniliforme (DM) is a well-known plant-derived extract that is widely used in Oriental medicine. DM and its chemical constituents have been reported to have a variety of pharmacological effects, including anti-oxidative, anti-inflammatory, and anti-tumor activities; however, no reports discuss the beneficial effects of DM on bone diseases such as osteoporosis. Thus, we investigated the relationship between DM and osteoclasts, cells that function in bone resorption. We found that DM significantly reduced receptor activator of nuclear factor kappa-B ligand (RANKL)-induced tartrate-resistant acid phosphatase (TRAP)-positive osteoclast formation; DM directly induced the down-regulation of c-Fos and nuclear factor of activated T cells c1 (NFATc1) without affecting other RANKL-dependent transduction pathways. In the later stages of osteoclast maturation, DM negatively regulated the organization of filamentous actin (F-actin), resulting in impaired bone-resorbing activity by the mature osteoclasts. In addition, micro-computed tomography (μ-CT) analysis of the murine model revealed that DM had a beneficial effect on lipopolysaccharide (LPS)-mediated bone erosion. Histological analysis showed that DM attenuated the degradation of trabecular bone matrix and formation of TRAP-positive osteoclasts in bone tissues. These results suggest that DM is a potential candidate for the treatment of metabolic bone disorders such as osteoporosis. Full article

(This article belongs to the Section Natural Products Chemistry)

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27 pages, 6069 KiB

Open AccessArticle

Optimization of Microwave-Assisted Extraction Conditions for Five Major Bioactive Compounds from Flos Sophorae Immaturus (Cultivars of Sophora japonica L.) Using Response Surface Methodology

by Jin-Liang Liu, Long-Yun Li and Guang-Hua He

Molecules 2016, 21(3), 296; https://doi.org/10.3390/molecules21030296 - 2 Mar 2016

Cited by 55 | Viewed by 8904

Abstract

Microwave-assisted extraction was applied to extract rutin; quercetin; genistein; kaempferol; and isorhamnetin from Flos Sophorae Immaturus. Six independent variables; namely; solvent type; particle size; extraction frequency; liquid-to-solid ratio; microwave power; and extraction time were examined. Response surface methodology using a central composite design [...] Read more.

Microwave-assisted extraction was applied to extract rutin; quercetin; genistein; kaempferol; and isorhamnetin from Flos Sophorae Immaturus. Six independent variables; namely; solvent type; particle size; extraction frequency; liquid-to-solid ratio; microwave power; and extraction time were examined. Response surface methodology using a central composite design was employed to optimize experimental conditions (liquid-to-solid ratio; microwave power; and extraction time) based on the results of single factor tests to extract the five major components in Flos Sophorae Immaturus. Experimental data were fitted to a second-order polynomial equation using multiple regression analysis. Data were also analyzed using appropriate statistical methods. Optimal extraction conditions were as follows: extraction solvent; 100% methanol; particle size; 100 mesh; extraction frequency; 1; liquid-to-solid ratio; 50:1; microwave power; 287 W; and extraction time; 80 s. A rapid and sensitive ultra-high performance liquid chromatography method coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (EIS-Q-TOF MS/MS) was developed and validated for the simultaneous determination of rutin; quercetin; genistein; kaempferol; and isorhamnetin in Flos Sophorae Immaturus. Chromatographic separation was accomplished on a Kinetex C₁₈ column (100 mm × 2.1 mm; 2.6 μm) at 40 °C within 5 min. The mobile phase consisted of 0.1% aqueous formic acid and acetonitrile (71:29; v/v). Isocratic elution was carried out at a flow rate of 0.35 mL/min. The constituents of Flos Sophorae Immaturus were simultaneously identified by EIS-Q-TOF MS/MS in multiple reaction monitoring mode. During quantitative analysis; all of the calibration curves showed good linear relationships (R² > 0.999) within the tested ranges; and mean recoveries ranged from 96.0216% to 101.0601%. The precision determined through intra- and inter-day studies showed an RSD% of <2.833%. These results demonstrate that the developed method is accurate and effective and could be readily utilized for the comprehensive quality control of Flos Sophorae Immaturus. Full article

(This article belongs to the Collection Bioactive Compounds)

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16 pages, 2964 KiB

Open AccessArticle

Anticancer Effects of Sinulariolide-Conjugated Hyaluronan Nanoparticles on Lung Adenocarcinoma Cells

by Kuan Yin Hsiao, Yi-Jhen Wu, Zi Nong Liu, Chin Wen Chuang, Han Hsiang Huang and Shyh Ming Kuo

Molecules 2016, 21(3), 297; https://doi.org/10.3390/molecules21030297 - 2 Mar 2016

Cited by 28 | Viewed by 7299

Abstract

Lung cancer is one of the most clinically challenging malignant diseases worldwide. Sinulariolide (SNL), extracted from the farmed coral species Sinularia flexibilis, has been used for suppressing malignant cells. For developing anticancer therapeutic agents, we aimed to find an alternative for non-small [...] Read more.

Lung cancer is one of the most clinically challenging malignant diseases worldwide. Sinulariolide (SNL), extracted from the farmed coral species Sinularia flexibilis, has been used for suppressing malignant cells. For developing anticancer therapeutic agents, we aimed to find an alternative for non-small cell lung cancer treatment by using SNL as the target drug. We investigated the SNL bioactivity on A549 lung cancer cells by conjugating SNL with hyaluronan nanoparticles to form HA/SNL aggregates by using a high-voltage electrostatic field system. SNL was toxic on A549 cells with an IC₅₀ of 75 µg/mL. The anticancer effects of HA/SNL aggregates were assessed through cell viability assay, apoptosis assays, cell cycle analyses, and western blotting. The size of HA/SNL aggregates was approximately 33–77 nm in diameter with a thin continuous layer after aggregating numerous HA nanoparticles. Flow cytometric analysis revealed that the HA/SNL aggregate-induced apoptosis was more effective at a lower SNL dose of 25 µg/mL than pure SNL. Western blotting indicated that caspases-3, -8, and -9 and Bcl-xL and Bax played crucial roles in the apoptotic signal transduction pathway. In summary, HA/SNL aggregates exerted stronger anticancer effects on A549 cells than did pure SNL via mitochondria-related pathways. 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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12 pages, 3273 KiB

Open AccessArticle

Rhubarb Anthraquinones Protect Rats against Mercuric Chloride (HgCl₂)-Induced Acute Renal Failure

by Dan Gao, Ling-Na Zeng, Pin Zhang, Zhi-Jie Ma, Rui-Sheng Li, Yan-Ling Zhao, Ya-Ming Zhang, Yu-Min Guo, Ming Niu, Zhao-Fang Bai, Xiao-He Xiao, Wei-Wei Gao and Jia-Bo Wang

Molecules 2016, 21(3), 298; https://doi.org/10.3390/molecules21030298 - 8 Mar 2016

Cited by 26 | Viewed by 8627

Abstract

Mercury (Hg) causes severe nephrotoxicity in subjects with excess exposure. This work attempted to identify whether a natural medicine—rhubarb—has protective effects against mercuric chloride (HgCl₂)-induced acute renal failure (ARF), and which of its components contributed most to the treatment. Total rhubarb [...] Read more.

Mercury (Hg) causes severe nephrotoxicity in subjects with excess exposure. This work attempted to identify whether a natural medicine—rhubarb—has protective effects against mercuric chloride (HgCl₂)-induced acute renal failure (ARF), and which of its components contributed most to the treatment. Total rhubarb extract (TR) were separated to the total anthraquinones (TA), the total tannins (TT) and remaining component extract (RC). Each extract was orally pre-administered to rats for five successive days followed by HgCl₂ injection to induce kidney injury. Subsequently, renal histopathology and biochemical examinations were performed in vitro to evaluate the protective effects. Pharmacological studies showed that TR and TA, but not TT or RC manifested significant protection activity against HgCl₂-induced ARF. There were also significant declines of serum creatine, urea nitrogen values and increases of total protein albumin levels in TR and TA treated groups compared to HgCl₂ alone (p < 0.05). At last, the major components in TA extract were further identified as anthraquinones by liquid chromatography coupled mass spectroscopy. This study thus provides observational evidences that rhubarb could ameliorate HgCl₂-induced ARF and its anthraquinones in particular are the effective components responsible for this activity in rhubarb extract. Full article

(This article belongs to the Section Medicinal Chemistry)

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11 pages, 815 KiB

Open AccessArticle

Synthesis of New Bis(3-hydroxy-4-pyridinone) Ligands as Chelating Agents for Uranyl Complexation

by Bo Jin, Rongzong Zheng, Rufang Peng and Shijin Chu

Molecules 2016, 21(3), 299; https://doi.org/10.3390/molecules21030299 - 8 Mar 2016

Cited by 2 | Viewed by 4892

Abstract

Five new bis(3-hydroxy-4-pyridinone) tetradentate chelators were synthesized in this study. The structures of these tetradentate chelators were characterized by ¹H-NMR, ¹³C-NMR, FT-IR, UV-vis, and mass spectral analyses. The binding abilities of these tetradentate chelators for uranyl ion at pH 7.4 were [...] Read more.

Five new bis(3-hydroxy-4-pyridinone) tetradentate chelators were synthesized in this study. The structures of these tetradentate chelators were characterized by ¹H-NMR, ¹³C-NMR, FT-IR, UV-vis, and mass spectral analyses. The binding abilities of these tetradentate chelators for uranyl ion at pH 7.4 were also determined by UV spectrophotometry in aqueous media. Results showed that the efficiencies of these chelating agents are dependent on the linker length. Ligand 4b is the best chelator and suitable for further studies. Full article

(This article belongs to the Section Medicinal Chemistry)

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13 pages, 1512 KiB

Open AccessArticle

Elucidation of Transport Mechanism of Paeoniflorin and the Influence of Ligustilide, Senkyunolide I and Senkyunolide A on Paeoniflorin Transport through Mdck-Mdr1 Cells as Blood–Brain Barrier in Vitro Model

by Peng-Yi Hu, Dan Liu, Qin Zheng, Qing Wu, Yu Tang and Ming Yang

Molecules 2016, 21(3), 300; https://doi.org/10.3390/molecules21030300 - 2 Mar 2016

Cited by 43 | Viewed by 7216

Abstract

The objectives of the present investigation were to: (1) elucidate the transport mechanism of paeoniflorin (PF) across MDCK-MDR1 monolayers; and (2) evaluate the effect of ligustilide (LIG), senkyunolide I (SENI) and senkyunolide A (SENA) on the transport of PF through blood–brain barrier so [...] Read more.

The objectives of the present investigation were to: (1) elucidate the transport mechanism of paeoniflorin (PF) across MDCK-MDR1 monolayers; and (2) evaluate the effect of ligustilide (LIG), senkyunolide I (SENI) and senkyunolide A (SENA) on the transport of PF through blood–brain barrier so as to explore the enhancement mechanism. Transport studies of PF were performed in both directions, from apical to basolateral side (A→B) and from basolateral to apical sides (B→A). Drug concentrations were analyzed by LC-MS/MS. PF showed relatively poor absorption in MDCK-MDR1 cells, apparent permeability coefficients (Papp) ranging from 0.587 × 10⁻⁶ to 0.705 × 10⁻⁶ cm/s. In vitro experiments showed that the transport of PF in both directions was concentration dependent and not saturable. The B→A/A→B permeability ER of PF was more than 2 in the MDCK-MDR1 cells, which indicated that the transport mechanism of PF might be passive diffusion as the dominating process with the active transportation mediated mechanism involved. The increased Papp of PF in A→B direction by EDTA-Na₂ suggested that PF was absorbed via the paracellular route. The P-gp inhibitor verapamil could significantly increase the transport of PF in A→B direction, and ER decreased from 2.210 to 0.690, which indicated that PF was P-gp substance. The transport of PF in A→B direction significantly increased when co-administrated with increasing concentrations of LIG, SENI and SENA. An increased cellular accumulation of Rho 123 and Western blot analysis indicated that LIG, SENI and SENA had increased the transport of PF in the BBB models attribute to down-regulate P-gp expression. A decrease in transepithelial electrical resistance (TEER) during the permeation experiment can be explained by the modulation and opening of the tight junctions caused by the permeation enhancer LIG, SENI and SENA. Full article

(This article belongs to the Section Medicinal Chemistry)

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14 pages, 1306 KiB

Open AccessArticle

Achillolide A Protects Astrocytes against Oxidative Stress by Reducing Intracellular Reactive Oxygen Species and Interfering with Cell Signaling

by Anat Elmann, Alona Telerman, Hilla Erlank, Rivka Ofir, Yoel Kashman and Elie Beit-Yannai

Molecules 2016, 21(3), 301; https://doi.org/10.3390/molecules21030301 - 2 Mar 2016

Cited by 7 | Viewed by 6114

Abstract

Achillolide A is a natural sesquiterpene lactone that we have previously shown can inhibit microglial activation. In this study we present evidence for its beneficial effects on astrocytes under oxidative stress, a situation relevant to neurodegenerative diseases and brain injuries. Viability of brain [...] Read more.

Achillolide A is a natural sesquiterpene lactone that we have previously shown can inhibit microglial activation. In this study we present evidence for its beneficial effects on astrocytes under oxidative stress, a situation relevant to neurodegenerative diseases and brain injuries. Viability of brain astrocytes (primary cultures) was determined by lactate dehydrogenase (LDH) activity, intracellular ROS levels were detected using 2′,7′-dichlorofluorescein diacetate, in vitro antioxidant activity was measured by differential pulse voltammetry, and protein phosphorylation was determined using specific ELISA kits. We have found that achillolide A prevented the H₂O₂-induced death of astrocytes, and attenuated the induced intracellular accumulation of reactive oxygen species (ROS). These activities could be attributed to the inhibition of the H₂O₂-induced phosphorylation of MAP/ERK kinase 1 (MEK1) and p44/42 mitogen-activated protein kinases (MAPK), and to the antioxidant activity of achillolide A, but not to H₂O₂ scavenging. This is the first study that demonstrates its protective effects on brain astrocytes, and its ability to interfere with MAPK activation. We propose that achillolide A deserves further evaluation for its potential to be developed as a drug for the prevention/treatment of neurodegenerative diseases and brain injuries where oxidative stress is part of the pathophysiology. Full article

(This article belongs to the Collection Neuroprotection Mediated by Natural Products and Their Chemical Derivatives)

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10 pages, 948 KiB

Open AccessArticle

Chemical Evidence for Potent Xanthine Oxidase Inhibitory Activity of Ethyl Acetate Extract of Citrus aurantium L. Dried Immature Fruits

by Kun Liu, Wei Wang, Bing-Hua Guo, Hua Gao, Yang Liu, Xiao-Hong Liu, Hui-Li Yao and Kun Cheng

Molecules 2016, 21(3), 302; https://doi.org/10.3390/molecules21030302 - 2 Mar 2016

Cited by 48 | Viewed by 8113

Abstract

Xanthine oxidase is a key enzyme which can catalyze hypoxanthine and xanthine to uric acid causing hyperuricemia in humans. Xanthine oxidase inhibitory activities of 24 organic extracts of four species belonging to Citrus genus of the family Rutaceae were assayed in vitro. [...] Read more.

Xanthine oxidase is a key enzyme which can catalyze hypoxanthine and xanthine to uric acid causing hyperuricemia in humans. Xanthine oxidase inhibitory activities of 24 organic extracts of four species belonging to Citrus genus of the family Rutaceae were assayed in vitro. Since the ethyl acetate extract of C. aurantium dried immature fruits showed the highest xanthine oxidase inhibitory activity, chemical evidence for the potent inhibitory activity was clarified on the basis of structure identification of the active constituents. Five flavanones and two polymethoxyflavones were isolated and evaluated for inhibitory activity against xanthine oxidase in vitro. Of the compounds, hesperetin showed more potent inhibitory activity with an IC₅₀ value of 16.48 μM. For the first time, this study provides a rational basis for the use of C. aurantium dried immature fruits against hyperuricemia. Full article

(This article belongs to the Collection Bioactive Compounds)

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11 pages, 419 KiB

Open AccessReview

Constituents of Saffron (Crocus sativus L.) as Potential Candidates for the Treatment of Anxiety Disorders and Schizophrenia

by Nikolaos Pitsikas

Molecules 2016, 21(3), 303; https://doi.org/10.3390/molecules21030303 - 2 Mar 2016

Cited by 82 | Viewed by 13000

Abstract

Anxiety disorders and schizophrenia are common public health issues. The dried stigma of the plant Crocus sativus L., (C. sativus) commonly known as saffron are used in folk medicine for various purposes. Several lines of evidence suggest that C. sativus, [...] Read more.

Anxiety disorders and schizophrenia are common public health issues. The dried stigma of the plant Crocus sativus L., (C. sativus) commonly known as saffron are used in folk medicine for various purposes. Several lines of evidence suggest that C. sativus, crocins and safranal are implicated in anxiety and schizophrenia. Here, I intend to critically review advances in research of these emerging molecules for the treatment of anxiety and schizophrenia, discuss their advantages over currently used anxiolytics and neuroleptics, as well remaining challenges. Current analysis shows that C. sativus and its components might be a promising class of compounds for the treatment of the above mentioned psychiatric diseases. Full article

(This article belongs to the Special Issue Saffron (Crocus sativus, L.): Omics and Other Techniques in Authenticity, Quality and Bioactivity Studies)

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8 pages, 592 KiB

Open AccessReview

Anti-Oxidant, Anti-Inflammatory and Anti-Angiogenic Properties of Resveratrol in Ocular Diseases

by Allan Lançon, Raffaele Frazzi and Norbert Latruffe

Molecules 2016, 21(3), 304; https://doi.org/10.3390/molecules21030304 - 2 Mar 2016

Cited by 109 | Viewed by 12077

Abstract

Resveratrol (3,4′,5 trihydroxy-trans-stilbene) is one of the best known phytophenols with pleiotropic properties. It is a phytoalexin produced by vine and it leads to the stimulation of natural plant defenses but also exhibits many beneficial effects in animals and humans by acting on [...] Read more.

Resveratrol (3,4′,5 trihydroxy-trans-stilbene) is one of the best known phytophenols with pleiotropic properties. It is a phytoalexin produced by vine and it leads to the stimulation of natural plant defenses but also exhibits many beneficial effects in animals and humans by acting on a wide range of organs and tissues. These include the prevention of cardiovascular diseases, anti-cancer potential, neuroprotective effects, homeostasia maintenance, aging delay and a decrease in inflammation. Age-related macular degeneration (AMD) is one of the main causes of deterioration of vision in adults in developed countries This review deals with resveratrol and ophthalmology by focusing on the antioxidant, anti-inflammatory, and anti-angiogenic effects of this molecule. The literature reports that resveratrol is able to act on various cell types of the eye by increasing the level of natural antioxidant enzymatic and molecular defenses. Resveratrol anti-inflammatory effects are due to its capacity to limit the expression of pro-inflammatory factors, such as interleukins and prostaglandins, and also to decrease the chemo-attraction and recruitment of immune cells to the inflammatory site. In addition to this, resveratrol was shown to possess anti-VEGF effects and to inhibit the proliferation and migration of vascular endothelial cells. Resveratrol has the potential to be used in a range of human ocular diseases and conditions, based on animal models and in vitro experiments. Full article

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

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19 pages, 2918 KiB

Open AccessReview

Nanotechnology Formulations for Antibacterial Free Fatty Acids and Monoglycerides

by Joshua A. Jackman, Bo Kyeong Yoon, Danlin Li and Nam-Joon Cho

Molecules 2016, 21(3), 305; https://doi.org/10.3390/molecules21030305 - 3 Mar 2016

Cited by 89 | Viewed by 21812

Abstract

Free fatty acids and monoglycerides have long been known to possess broad-spectrum antibacterial activity that is based on lytic behavior against bacterial cell membranes. Considering the growing challenges of drug-resistant bacteria and the need for new classes of antibiotics, the wide prevalence, affordable [...] Read more.

Free fatty acids and monoglycerides have long been known to possess broad-spectrum antibacterial activity that is based on lytic behavior against bacterial cell membranes. Considering the growing challenges of drug-resistant bacteria and the need for new classes of antibiotics, the wide prevalence, affordable cost, and broad spectrum of fatty acids and monoglycerides make them attractive agents to develop for healthcare and biotechnology applications. The aim of this review is to provide a brief introduction to the history of antimicrobial lipids and their current status and challenges, and to present a detailed discussion of ongoing research efforts to develop nanotechnology formulations of fatty acids and monoglycerides that enable superior in vitro and in vivo performance. Examples of nano-emulsions, liposomes, solid lipid nanoparticles, and controlled release hydrogels are presented in order to highlight the potential that lies ahead for fatty acids and monoglycerides as next-generation antibacterial solutions. Possible application routes and future directions in research and development are also discussed. Full article

(This article belongs to the Collection Antibiotics & Superbugs: New Strategies to Combat Antimicrobial Resistance)

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11 pages, 2248 KiB

Open AccessArticle

Expression and Functional Activity of the Human Bitter Taste Receptor TAS2R38 in Human Placental Tissues and JEG-3 Cells

by Ute Wölfle, Floriana A. Elsholz, Astrid Kersten, Birgit Haarhaus, Udo Schumacher and Christoph M. Schempp

Molecules 2016, 21(3), 306; https://doi.org/10.3390/molecules21030306 - 3 Mar 2016

Cited by 41 | Viewed by 12473

Abstract

Bitter taste receptors (TAS2Rs) are expressed in mucous epithelial cells of the tongue but also outside the gustatory system in epithelial cells of the colon, stomach and bladder, in the upper respiratory tract, in the cornified squamous epithelium of the skin as well [...] Read more.

Bitter taste receptors (TAS2Rs) are expressed in mucous epithelial cells of the tongue but also outside the gustatory system in epithelial cells of the colon, stomach and bladder, in the upper respiratory tract, in the cornified squamous epithelium of the skin as well as in airway smooth muscle cells, in the testis and in the brain. In the present work we addressed the question if bitter taste receptors might also be expressed in other epithelial tissues as well. By staining a tissue microarray with 45 tissue spots from healthy human donors with an antibody directed against the best characterized bitter taste receptor TAS2R38, we observed an unexpected strong TAS2R38 expression in the amniotic epithelium, syncytiotrophoblast and decidua cells of the human placenta. To analyze the functionality we first determined the TAS2R38 expression in the placental cell line JEG-3. Stimulation of these cells with diphenidol, a clinically used antiemetic agent that binds TAS2Rs including TAS2R38, demonstrated the functionality of the TAS2Rs by inducing calcium influx. Restriction enzyme based detection of the TAS2R38 gene allele identified JEG-3 cells as PTC (phenylthiocarbamide)-taster cell line. Calcium influx induced by PTC in JEG-3 cells could be inhibited with the recently described TAS2R38 inhibitor probenecid and proved the specificity of the TAS2R38 activation. The expression of TAS2R38 in human placental tissues points to further new functions and hitherto unknown endogenous ligands of TAS2Rs far beyond bitter tasting. Full article

(This article belongs to the Collection Recent Advances in Flavors and Fragrances)

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12 pages, 2330 KiB

Open AccessArticle

Synthesis of Isoxazole and 1,2,3-Triazole Isoindole Derivatives via Silver- and Copper-Catalyzed 1,3-Dipolar Cycloaddition Reaction

by Mohamed Mehdi Rammah, Wafa Gati, Hasan Mtiraoui, Mohamed El Baker Rammah, Kabula Ciamala, Michael Knorr, Yoann Rousselin and Marek M. Kubicki

Molecules 2016, 21(3), 307; https://doi.org/10.3390/molecules21030307 - 4 Mar 2016

Cited by 11 | Viewed by 7918

Abstract

The CuI- or Ag₂CO₃-catalyzed [3+2] cycloaddition of propargyl-substituted dihydroisoindolin-1-one (3) with arylnitrile oxides 1a–d (Ar = Ph, p-MeC₆H₄, p-MeOC₆H₄, p-ClC₆H₄) produces in good yields [...] Read more.

The CuI- or Ag₂CO₃-catalyzed [3+2] cycloaddition of propargyl-substituted dihydroisoindolin-1-one (3) with arylnitrile oxides 1a–d (Ar = Ph, p-MeC₆H₄, p-MeOC₆H₄, p-ClC₆H₄) produces in good yields novel 3,5-disubstituted isoxazoles 4 of the ethyl-2-benzyl-3-oxo-1-((3-arylisoxazol-5yl)methyl)-2,3-dihydro-1H-isoindole-1-carboxylate type. With aryl azides 2a–d (Ar = Ph, p-MeC₆H₄, p-OMeC₆H₄, p-ClC₆H₄), a series of 1,4-disubstituted 1,2,3-triazoles 6 (ethyl-2-benzyl-3-oxo-1-((1-aryl-1H-1,2,3-triazol-4-yl)methyl)-2,3-dihydro-1H-isoindole-1-carboxylates) was obtained. The reactions proceed in a regioselective manner affording exclusively racemic adducts 4 and 6. Compared to the uncatalyzed cycloaddition, the yields are significantly improved in the presence of CuI as catalyst, without alteration of the selectivity. The regio- and stereochemistry of the cycloadducts has been corroborated by an X-ray diffraction study of 4a, and in the case of 6a by XH-correlation and HMBC spectra. Full article

(This article belongs to the Special Issue Coinage Metal (Copper, Silver, and Gold) Catalysis)

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8 pages, 1720 KiB

Open AccessArticle

Casbane Diterpenes from Red Sea Coral Sinularia polydactyla

by Mohamed-Elamir F. Hegazy, Tarik A. Mohamed, Abdelsamed I. Elshamy, Montaser A. Al-Hammady, Shinji Ohta and Paul W. Paré

Molecules 2016, 21(3), 308; https://doi.org/10.3390/molecules21030308 - 3 Mar 2016

Cited by 26 | Viewed by 6502

Abstract

The soft coral genus Sinularia is a rich source of bioactive metabolites containing a diverse array of chemical structures. A solvent extract of Sinularia polydactyla resulted in the isolation of three new casbane diterpenes: sinularcasbane M (1), sinularcasbane N (2) and sinularcasbane O [...] Read more.

The soft coral genus Sinularia is a rich source of bioactive metabolites containing a diverse array of chemical structures. A solvent extract of Sinularia polydactyla resulted in the isolation of three new casbane diterpenes: sinularcasbane M (1), sinularcasbane N (2) and sinularcasbane O (3); in addition, known metabolites (4–5) were isolated. Compounds were elucidated on the basis of spectroscopic analyses; the absolute configuration was confirmed by X-ray analysis. Full article

(This article belongs to the Section Natural Products Chemistry)

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13 pages, 4312 KiB

Open AccessArticle

Anti-Metastatic Properties of a Marine Bacterial Exopolysaccharide-Based Derivative Designed to Mimic Glycosaminoglycans

by Dominique Heymann, Carmen Ruiz-Velasco, Julie Chesneau, Jacqueline Ratiskol, Corinne Sinquin and Sylvia Colliec-Jouault

Molecules 2016, 21(3), 309; https://doi.org/10.3390/molecules21030309 - 4 Mar 2016

Cited by 25 | Viewed by 6145

Abstract

Osteosarcoma is the most frequent malignant primary bone tumor characterized by a high potency to form lung metastases. In this study, the effect of three oversulfated low molecular weight marine bacterial exopolysaccharides (OS-EPS) with different molecular weights (4, 8 and 15 kDa) were [...] Read more.

Osteosarcoma is the most frequent malignant primary bone tumor characterized by a high potency to form lung metastases. In this study, the effect of three oversulfated low molecular weight marine bacterial exopolysaccharides (OS-EPS) with different molecular weights (4, 8 and 15 kDa) were first evaluated in vitro on human and murine osteosarcoma cell lines. Different biological activities were studied: cell proliferation, cell adhesion and migration, matrix metalloproteinase expression. This in vitro study showed that only the OS-EPS 15 kDa derivative could inhibit the invasiveness of osteosarcoma cells with an inhibition rate close to 90%. Moreover, this derivative was potent to inhibit both migration and invasiveness of osteosarcoma cell lines; had no significant effect on their cell cycle; and increased slightly the expression of MMP-9, and more highly the expression of its physiological specific tissue inhibitor TIMP-1. Then, the in vivo experiments showed that the OS-EPS 15 kDa derivative had no effect on the primary osteosarcoma tumor induced by osteosarcoma cell lines but was very efficient to inhibit the establishment of lung metastases in vivo. These results can help to better understand the mechanisms of GAGs and GAG-like derivatives in the biology of the tumor cells and their interactions with the bone environment to develop new therapeutic strategies. Full article

(This article belongs to the Collection Bioactive Compounds)

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27 pages, 7933 KiB

Open AccessReview

Porphyrins as Catalysts in Scalable Organic Reactions

by Juan C. Barona-Castaño, Christian C. Carmona-Vargas, Timothy J. Brocksom and Kleber T. De Oliveira

Molecules 2016, 21(3), 310; https://doi.org/10.3390/molecules21030310 - 8 Mar 2016

Cited by 253 | Viewed by 17285

Abstract

Catalysis is a topic of continuous interest since it was discovered in chemistry centuries ago. Aiming at the advance of reactions for efficient processes, a number of approaches have been developed over the last 180 years, and more recently, porphyrins occupy an important [...] Read more.

Catalysis is a topic of continuous interest since it was discovered in chemistry centuries ago. Aiming at the advance of reactions for efficient processes, a number of approaches have been developed over the last 180 years, and more recently, porphyrins occupy an important role in this field. Porphyrins and metalloporphyrins are fascinating compounds which are involved in a number of synthetic transformations of great interest for industry and academy. The aim of this review is to cover the most recent progress in reactions catalysed by porphyrins in scalable procedures, thus presenting the state of the art in reactions of epoxidation, sulfoxidation, oxidation of alcohols to carbonyl compounds and C–H functionalization. In addition, the use of porphyrins as photocatalysts in continuous flow processes is covered. Full article

(This article belongs to the Special Issue Tetrapyrrolic Macrocycles: Synthesis, Functionalization and Applications)

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11 pages, 1353 KiB

Open AccessArticle

bis-Nitrile and bis-Dialkylcyanamide Platinum(II) Complexes as Efficient Catalysts for Hydrosilylation Cross-Linking of Siloxane Polymers

by Regina M. Islamova, Mikhail V. Dobrynin, Daniil M. Ivanov, Andrey V. Vlasov, Elena V. Kaganova, Galina V. Grigoryan and Vadim Yu. Kukushkin

Molecules 2016, 21(3), 311; https://doi.org/10.3390/molecules21030311 - 5 Mar 2016

Cited by 29 | Viewed by 8729

Abstract

cis- and trans-Isomers of the platinum(II) nitrile complexes [PtCl₂(NCR)₂] (R = NMe₂, N(C₅H₁₀), Ph, CH₂Ph) were examined as catalysts for hydrosilylation cross-linking of vinyl-terminated polydimethylsiloxane and trimethylsilyl-terminated poly(dimethylsiloxane-co [...] Read more.

cis- and trans-Isomers of the platinum(II) nitrile complexes [PtCl₂(NCR)₂] (R = NMe₂, N(C₅H₁₀), Ph, CH₂Ph) were examined as catalysts for hydrosilylation cross-linking of vinyl-terminated polydimethylsiloxane and trimethylsilyl-terminated poly(dimethylsiloxane-co-ethylhydrosiloxane) producing high quality silicone rubbers. Among the tested platinum species the cis-complexes are much more active catalysts than their trans-congeners and for all studied platinum complexes cis-[PtCl₂(NCCH₂Ph)₂] exhibits the best catalytic activity (room temperature, c = 1.0 × 10⁻⁴ mol/L, τ_pot-life 60 min, τ_curing 6 h). Although cis-[PtCl₂(NCCH₂Ph)₂] is less active than the widely used Karstedt’s catalyst, its application for the cross-linking can be performed not only at room temperature (c = 1.0 × 10⁻⁴ mol/L), but also, more efficiently, at 80 °C (c = 1.0 × 10⁻⁴–1.0 × 10⁻⁵ mol/L) and it prevents adherence of the formed silicone rubbers to equipment. The usage of the cis- and trans-[PtCl₂(NCR)₂] complexes as the hydrosilylation catalysts do not require any inhibitors and, moreover, the complexes and their mixtures with vinyl- and trimethylsilyl terminated polysiloxanes are shelf-stable in air. Tested catalysts do not form colloid platinum particles after the cross-linking. Full article

(This article belongs to the Special Issue Metal Mediated Activation of Small Molecules)

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9 pages, 1897 KiB

Open AccessArticle

Synthesis, Characterization and in Vitro Evaluation of Manganese Ferrite (MnFe₂O₄) Nanoparticles for Their Biocompatibility with Murine Breast Cancer Cells (4T1)

by Samikannu Kanagesan, Sidek Bin Ab Aziz, Mansor Hashim, Ismayadi Ismail, Subramani Tamilselvan, Noorjahan Banu Binti Mohammed Alitheen, Mallappa Kumara Swamy and Bandaru Purna Chandra Rao

Molecules 2016, 21(3), 312; https://doi.org/10.3390/molecules21030312 - 11 Mar 2016

Cited by 65 | Viewed by 9314

Abstract

Manganese ferrite (MnFe₂O₄) magnetic nanoparticles were successfully prepared by a sol-gel self-combustion technique using iron nitrate and manganese nitrate, followed by calcination at 150 °C for 24 h. Calcined sample was systematically characterized by X-ray diffraction (XRD), Fourier transform [...] Read more.

Manganese ferrite (MnFe₂O₄) magnetic nanoparticles were successfully prepared by a sol-gel self-combustion technique using iron nitrate and manganese nitrate, followed by calcination at 150 °C for 24 h. Calcined sample was systematically characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), and vibrational sample magnetometry (VSM) in order to identify the crystalline phase, functional group, morphology, particle size, shape and magnetic behavior. It was observed that the resultant spinal ferrites obtained at low temperature exhibit single phase, nanoparticle size and good magnetic behavior. The study results have revealed the existence of a potent dose dependent cytotoxic effect of MnFe₂O₄ nanoparticles against 4T1 cell lines at varying concentrations with IC₅₀ values of 210, 198 and 171 μg/mL after 24 h, 48 h and 72 h of incubation, respectively. Cells exposed to higher concentrations of nanoparticles showed a progressive increase of apoptotic and necrotic activity. Below 125 μg/mL concentration the nanoparticles were biocompatible with 4T1 cells. Full article

(This article belongs to the Special Issue Pharmaceutical Nanotechnology: Novel Approaches)

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12 pages, 4479 KiB

Open AccessArticle

Inulin and Fibersol-2 Combined Have Hypolipidemic Effects on High Cholesterol Diet-Induced Hyperlipidemia in Hamsters

by Wen-Ching Huang, Che-Li Lin, Yi-Ju Hsu, Yen-Shuo Chiu, Yi-Ming Chen, Ming-Fang Wu, Chi-Chang Huang and Ming-Fu Wang

Molecules 2016, 21(3), 313; https://doi.org/10.3390/molecules21030313 - 5 Mar 2016

Cited by 24 | Viewed by 9588

Abstract

The resistant carbohydrates, inulin, and Fibersol-2, belong to soluble dietary fibers and are considered important prebiotics that maintain biological functions, including glucose homeostasis, lipid regulation, colon disease prevention, and prebiotics characteristics. However, few studies have investigated Fibersol-2 alone or in combination with inulin [...] Read more.

The resistant carbohydrates, inulin, and Fibersol-2, belong to soluble dietary fibers and are considered important prebiotics that maintain biological functions, including glucose homeostasis, lipid regulation, colon disease prevention, and prebiotics characteristics. However, few studies have investigated Fibersol-2 alone or in combination with inulin to assess a pooled effect on modulation of hyperlipidemia. We aimed to investigate the effects of this combined supplement (defined as InF) on hamsters fed a 0.2% cholesterol and 10% lard diet (i.e., high-cholesterol diet, HCD) to induce hyperlipidemia. A total of 40 male hamsters were randomly assigned to five groups (n = 8 per group) for treatment: standard diet, vehicle (control); or vehicle or InF supplementation by oral gavage at 0, 864, 1727, or 2591 mg/kg/day for eight weeks, designated HCD, InF-1X, InF-2X, and InF-3X groups, respectively. The hypolipidemic efficacy and safety of InF supplementation was assessed by serum lipid indexes, hepatic and fecal lipid content, and histology. InF supplementation significantly improved serum levels of triacylglycerol (TG) and low-density lipoprotein cholesterol (LDL-C) and the ratio of LDL-C/HDL-C after two-week treatment, and reduced serum total cholesterol (TC) levels after four-week administration. After eight-week supplementation, InF supplementation dose-dependently improved serum levels of TC, TG, HDL-C, and LDL-C; LDL-C/HDL-C ratio; and hepatic TC and TG levels. It inhibited TC absorption by feces elimination. Our study provides experiment-based evidence to support that this prebiotics remedy may be useful in preventing or treating hyperlipidemia. Full article

(This article belongs to the Section Medicinal Chemistry)

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22 pages, 2889 KiB

Open AccessReview

Pharmacokinetic and Metabolic Characteristics of Herb-Derived Khellactone Derivatives, A Class of Anti-HIV and Anti-Hypertensive: A Review

by Wanghui Jing, Ruilin Liu, Wei Du, Zhimin Luo, Pengqi Guo, Ting Zhang, Aiguo Zeng, Chun Chang and Qiang Fu

Molecules 2016, 21(3), 314; https://doi.org/10.3390/molecules21030314 - 8 Mar 2016

Cited by 6 | Viewed by 6316

Abstract

A vast number of structural modifications have been performed for khellactone derivatives (KDs) that have been widely concerned owing to their diverse biological properties, including anti-hypertension, anti-HIV, reversing P-glycoprotein (P-gp) mediated multidrug resistance, and anti-inflammation effects, to find the most active entity. However, [...] Read more.

A vast number of structural modifications have been performed for khellactone derivatives (KDs) that have been widely concerned owing to their diverse biological properties, including anti-hypertension, anti-HIV, reversing P-glycoprotein (P-gp) mediated multidrug resistance, and anti-inflammation effects, to find the most active entity. However, extensive metabolism of KDs results in poor oral bioavailability, thus hindering the clinical trial performance of those components. The primary metabolic pathways have been revealed as hydrolysis, oxidation, acyl migration, and glucuronidation, while carboxylesterases and cytochrome P450 3A (CPY3A), as well as UDP-glucuronosyltransferases (UGTs) primarily mediate these metabolic pathways. Attention was mainly paid to the pharmacological features, therapeutic mechanisms and structure-activity relationships of KDs in previous reviews, whereas their pharmacokinetic and metabolic characteristics have seldom been discussed. In the present review, KDs’ metabolism and their pharmacokinetic properties are summarized. In addition, the structure-metabolism relationships of KDs and the potential drug-drug interactions (DDIs) induced by KDs were also extensively discussed. The polarity, the acyl groups substituted at C-3′ and C-4′ positions, the configuration of C-3′ and C-4′, and the moieties substituted at C-3 and C-4 positions play the determinant roles for the metabolic profiles of KDs. Contributions from CYP3A4, UGT1A1, P-gp, and multidrug resistance-associated protein 2 have been disclosed to be primary for the potential DDIs. The review is expected to provide meaningful information and helpful guidelines for the further development of KDs. Full article

(This article belongs to the Section Medicinal Chemistry)

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12 pages, 1885 KiB

Open AccessArticle

Isolation, Purification and Quantification of Ginsenoside F₅ and F₃ Isomeric Compounds from Crude Extracts of Flower Buds of Panax ginseng

by Ke-Ke Li, Fei Xu and Xiao-Jie Gong

Molecules 2016, 21(3), 315; https://doi.org/10.3390/molecules21030315 - 9 Mar 2016

Cited by 16 | Viewed by 6751

Abstract

In this paper, the isolation, purification and quantification of ginsenoside F₅ and F₃ isomeric compounds from crude extracts of flower buds of Panax ginseng (CEFBPG) was investigated by reversed-phase high-performance liquid chromatography (RP-HPLC) for the first time. The satisfied separation at [...] Read more.

In this paper, the isolation, purification and quantification of ginsenoside F₅ and F₃ isomeric compounds from crude extracts of flower buds of Panax ginseng (CEFBPG) was investigated by reversed-phase high-performance liquid chromatography (RP-HPLC) for the first time. The satisfied separation at analytical scale was achieved using a Zorbax Eclipse XDB C-18 column with a ternary mobile phase of acetonitrile–water–phosphoric acid (28:71:1) at a flow rate of 1.0 mL/min within 40 min. UV detection was set at 203 nm. Ginsenoside F₅ and F₃ was 4.21 mg and 5.13 mg in 1 g flower buds of P. ginseng (FBPG), respectively. The preparation of ginsenoside F₅ and F₃ at semi-preparative scale was performed by using a Daisogel C-18 column and gradient elution system of acetonitrile–water (32:68 → 28:72) at a flow rate of 10 mL/min with a sample load of 20–30 mg, and yielded ginsenosides in purity of more than 96%. Their structures were characterized by NMR and high resolution electrospray ionization mass spectrometry (HRESIMS). All the method validations showed acceptable limits. The results indicate a new source to obtain ginsenoside F₅ and F₃, and show that the method developed here appears to be reliable for simultaneously preparing them from CEFBPG. Full article

(This article belongs to the Collection Herbal Medicine Research)

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15 pages, 3302 KiB

Open AccessArticle

Cloning, Expression Profiling and Functional Analysis of CnHMGS, a Gene Encoding 3-hydroxy-3-Methylglutaryl Coenzyme A Synthase from Chamaemelum nobile

by Shuiyuan Cheng, Xiaohui Wang, Feng Xu, Qiangwen Chen, Tingting Tao, Jing Lei, Weiwei Zhang, Yongling Liao, Jie Chang and Xingxiang Li

Molecules 2016, 21(3), 316; https://doi.org/10.3390/molecules21030316 - 8 Mar 2016

Cited by 14 | Viewed by 6490

Abstract

Roman chamomile (Chamaemelum nobile L.) is renowned for its production of essential oils, which major components are sesquiterpenoids. As the important enzyme in the sesquiterpenoid biosynthesis pathway, 3-hydroxy-3-methylglutaryl coenzyme A synthase (HMGS) catalyze the crucial step in the mevalonate pathway in plants. [...] Read more.

Roman chamomile (Chamaemelum nobile L.) is renowned for its production of essential oils, which major components are sesquiterpenoids. As the important enzyme in the sesquiterpenoid biosynthesis pathway, 3-hydroxy-3-methylglutaryl coenzyme A synthase (HMGS) catalyze the crucial step in the mevalonate pathway in plants. To isolate and identify the functional genes involved in the sesquiterpene biosynthesis of C. nobile L., a HMGS gene designated as CnHMGS (GenBank Accession No. KU529969) was cloned from C. nobile. The cDNA sequence of CnHMGS contained a 1377 bp open reading frame encoding a 458-amino-acid protein. The sequence of the CnHMGS protein was highly homologous to those of HMGS proteins from other plant species. Phylogenetic tree analysis revealed that CnHMGS clustered with the HMGS of Asteraceae in the dicotyledon clade. Further functional complementation of CnHMGS in the mutant yeast strain YSC6274 lacking HMGS activity demonstrated that the cloned CnHMGS cDNA encodes a functional HMGS. Transcript profile analysis indicated that CnHMGS was preferentially expressed in flowers and roots of C. nobile. The expression of CnHMGS could be upregulated by exogenous elicitors, including methyl jasmonate and salicylic acid, suggesting that CnHMGS was elicitor-responsive. The characterization and expression analysis of CnHMGS is helpful to understand the biosynthesis of sesquiterpenoid in C. nobile at the molecular level and also provides molecular wealth for the biotechnological improvement of this important medicinal plant. Full article

(This article belongs to the Special Issue Biosynthesis of Natural Products)

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12 pages, 13344 KiB

Open AccessArticle

Pharmacokinetic-Pharmacodynamic Modeling to Study the Antipyretic Effect of Qingkailing Injection on Pyrexia Model Rats

by Zhixin Zhang, Lingling Qin, Long Peng, Qingqing Zhang, Qing Wang, Zhiwei Lu, Yuelin Song and Xiaoyan Gao

Molecules 2016, 21(3), 317; https://doi.org/10.3390/molecules21030317 - 7 Mar 2016

Cited by 30 | Viewed by 8492

Abstract

Qingkailing injection (QKLI) is a modern Chinese medicine preparation derived from a well-known classical formulation, An-Gong-Niu-Huang Wan. Although the clinical efficacy of QKLI has been well defined, its severe adverse drug reactions (ADRs) were extensively increased. Through thorough attempts to reduce ADR rates, [...] Read more.

Qingkailing injection (QKLI) is a modern Chinese medicine preparation derived from a well-known classical formulation, An-Gong-Niu-Huang Wan. Although the clinical efficacy of QKLI has been well defined, its severe adverse drug reactions (ADRs) were extensively increased. Through thorough attempts to reduce ADR rates, it was realized that the effect-based rational use plays the key role in clinical practices. Hence, the pharmacokinetic-pharmacodynamic (PK-PD) model was introduced in the present study, aiming to link the pharmacokinetic profiles with the therapeutic outcomes of QKLI, and subsequently to provide valuable guidelines for the rational use of QKLI in clinical settings. The PK properties of the six dominant ingredients in QKLI were compared between the normal treated group (NTG) and the pyrexia model group (MTG). Rectal temperatures were measured in parallel with blood sampling for NTG, MTG, model control group (MCG), and normal control group (NCG). Baicalin and geniposide exhibited appropriate PK parameters, and were selected as the PK markers to map the antipyretic effect of QKLI. Then, a PK-PD model was constructed upon the bacalin and geniposide plasma concentrations vs. the rectal temperature variation values, by a two-compartment PK model with a Sigmoid E_max PD model to explain the time delay between the drug plasma concentration of PK markers and the antipyretic effect after a single dose administration of QKLI. The findings obtained would provide fundamental information to propose a more reasonable dosage regimen and improve the level of individualized drug therapy in clinical settings. Full article

(This article belongs to the Section Medicinal Chemistry)

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11 pages, 1518 KiB

Open AccessArticle

Continuous-Flow Synthesis of Deuterium-Labeled Antidiabetic Chalcones: Studies towards the Selective Deuteration of the Alkynone Core

by Sándor B. Ötvös, Chi-Ting Hsieh, Yang-Chang Wu, Jih-Heng Li, Fang-Rong Chang and Ferenc Fülöp

Molecules 2016, 21(3), 318; https://doi.org/10.3390/molecules21030318 - 7 Mar 2016

Cited by 25 | Viewed by 8864

Abstract

Flow chemistry-based syntheses of deuterium-labeled analogs of important antidiabetic chalcones were achieved via highly controlled partial C≡C bond deuteration of the corresponding 1,3-diphenylalkynones. The benefits of a scalable continuous process in combination with on-demand electrolytic D₂ gas generation were exploited to suppress [...] Read more.

Flow chemistry-based syntheses of deuterium-labeled analogs of important antidiabetic chalcones were achieved via highly controlled partial C≡C bond deuteration of the corresponding 1,3-diphenylalkynones. The benefits of a scalable continuous process in combination with on-demand electrolytic D₂ gas generation were exploited to suppress undesired over-reactions and to maximize reaction rates simultaneously. The novel deuterium-containing chalcone derivatives may have interesting biological effects and improved metabolic properties as compared with the parent compounds. Full article

(This article belongs to the Special Issue Recent Advances in Flow Chemistry)

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18 pages, 1376 KiB

Open AccessArticle

Differential Response of Two Human Breast Cancer Cell Lines to the Phenolic Extract from Flaxseed Oil

by Angela Sorice, Eliana Guerriero, Maria Grazia Volpe, Francesca Capone, Francesco La Cara, Gennaro Ciliberto, Giovanni Colonna and Susan Costantini

Molecules 2016, 21(3), 319; https://doi.org/10.3390/molecules21030319 - 8 Mar 2016

Cited by 17 | Viewed by 6579

Abstract

Many studies have evidenced that the phenolic components from flaxseed (FS) oil have potential health benefits. The effect of the phenolic extract from FS oil has been evaluated on two human breast cancer cell lines, MCF7 and MDA-MB231, and on the human non-cancerous [...] Read more.

Many studies have evidenced that the phenolic components from flaxseed (FS) oil have potential health benefits. The effect of the phenolic extract from FS oil has been evaluated on two human breast cancer cell lines, MCF7 and MDA-MB231, and on the human non-cancerous breast cell line, MCF10A, by SRB assay, cellular death, cell cycle, cell signaling, lipid peroxidation and expression of some key genes. We have evidenced that the extract shows anti-proliferative activity on MCF7 cells by inducing cellular apoptosis, increase of the percentage of cells in G0/G1 phase and of lipid peroxidation, activation of the H2AX signaling pathway, and upregulation of a six gene signature. On the other hand, on the MDA-MB2131 cells we verified only an anti-proliferative activity, a weak lipid peroxidation, the activation of the PI3K signaling pathway and an up-regulation of four genes. Overall these data suggest that the extract has both cytotoxic and pro-oxidant effects only on MCF7 cells, and can act as a metabolic probe, inducing differences in the gene expression. For this purpose, we have performed an interactomic analysis, highlighting the existing associations. From this approach, we show that the phenotypic difference between the two cell lines can be explained through their differential response to the phenolic extract. Full article

(This article belongs to the Section Natural Products Chemistry)

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30 pages, 6779 KiB

Open AccessReview

Porphyrin Macrocycle Modification: Pyrrole Ring-Contracted or -Expanded Porphyrinoids

by Letícia D. Costa, Joana I.T. Costa and Augusto C. Tomé

Molecules 2016, 21(3), 320; https://doi.org/10.3390/molecules21030320 - 9 Mar 2016

Cited by 53 | Viewed by 10811

Abstract

In recent years, several synthetic strategies aiming at the peripheral functionalization of porphyrins were developed. Particularly interesting are those involving the modification of β-pyrrolic positions leading to pyrrole-modified porphyrins containing four-, five-, six- or seven-membered heterocycles. Azeteoporphyrins, porpholactones and morpholinoporphyrins are representative examples [...] Read more.

In recent years, several synthetic strategies aiming at the peripheral functionalization of porphyrins were developed. Particularly interesting are those involving the modification of β-pyrrolic positions leading to pyrrole-modified porphyrins containing four-, five-, six- or seven-membered heterocycles. Azeteoporphyrins, porpholactones and morpholinoporphyrins are representative examples of such porphyrinoids. These porphyrin derivatives have recently gained an increasing interest due to their potential application in PDT, as multimodal imaging contrast agents, NIR-absorbing dyes, optical sensors for oxygen, cyanide, hypochlorite and pH, and in catalysis. Full article

(This article belongs to the Special Issue Tetrapyrrolic Macrocycles: Synthesis, Functionalization and Applications)

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11 pages, 741 KiB

Open AccessArticle

Liquid Chromatography with Tandem Mass Spectrometry: A Sensitive Method for the Determination of Dehydrodiisoeugenol in Rat Cerebral Nuclei

by You-Bo Zhang, Xin-Bao Yang, Xiu-Wei Yang, Wei Xu, Fei Li and Frank J. Gonzezal

Molecules 2016, 21(3), 321; https://doi.org/10.3390/molecules21030321 - 9 Mar 2016

Cited by 15 | Viewed by 5614

Abstract

A new liquid chromatography–tandem mass spectrometry (LC-MS/MS) method is developed for the quantification of dehydrodiisoeugenol (DDIE) in rat cerebral nuclei after single intravenous administration. DDIE and daidzein (internal standard) were separated on a Diamonsil™ ODS C₁₈ column with methanol–water containing 0.1% formic [...] Read more.

A new liquid chromatography–tandem mass spectrometry (LC-MS/MS) method is developed for the quantification of dehydrodiisoeugenol (DDIE) in rat cerebral nuclei after single intravenous administration. DDIE and daidzein (internal standard) were separated on a Diamonsil™ ODS C₁₈ column with methanol–water containing 0.1% formic acid (81:19, v/v) as a mobile phase. Detection of DDIE was performed on a positive electrospray ionization source using a triple quadrupole mass spectrometer. DDIE and daidzein were monitored at m/z 327.2→188.0 and m/z 255.0→199.2, respectively, in multiple reaction monitoring mode. This method enabled quantification of DDIE in various brain areas, including, cortex, hippocampus, striatum, hypothalamus, cerebellum and brainstem, with high specificity, precision, accuracy, and recovery. The data herein demonstrate that our new LC-MS/MS method is highly sensitive and suitable for monitoring cerebral nuclei distribution of DDIE. Full article

(This article belongs to the Collection Bioactive Compounds)

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14 pages, 1999 KiB

Open AccessArticle

Proteomic Profiling of Iron Overload-Induced Human Hepatic Cells Reveals Activation of TLR2-Mediated Inflammatory Response

by Xiang Li, Shiwei Li, Mize Lu, Guohua Yang, Yunfeng Shen and Xin Zhou

Molecules 2016, 21(3), 322; https://doi.org/10.3390/molecules21030322 - 17 Mar 2016

Cited by 9 | Viewed by 5770

Abstract

Background: Hepatic iron overload is common in patients who have undergone hematopoietic cell transplantation (HCT) and may predispose to peri- and post-HCT toxicity. To better reveal more molecules that might be involved in iron overload-induced liver injury, we utilized proteomics to investigate differentially [...] Read more.

Background: Hepatic iron overload is common in patients who have undergone hematopoietic cell transplantation (HCT) and may predispose to peri- and post-HCT toxicity. To better reveal more molecules that might be involved in iron overload-induced liver injury, we utilized proteomics to investigate differentially expressed proteins in iron overload-induced hepatocytes vs. untreated hepatocytes. Methods and Results: HH4 hepatocytes were exposed to ferric ammonium citrate (FAC) to establish an in vitro iron overload model. Differentially expressed proteins initiated by the iron overload were studied by two-dimensional liquid chromatography tandem mass spectrometry (2D-LC-MS) analysis. We identified 93 proteins whose quantity statistically significantly changes under excess hepatocyte iron conditions. Gene Ontology (GO) analysis showed that these differentially expressed proteins in HH4 cells are involved in various biological process including endocytosis, response to wounding, di-, trivalent inorganic cation homeostasis, inflammatory response, positive regulation of cytokine production, and etc. Meanwhile, proteomics data revealed protein level of TLR2 and IL6ST significantly increased 7 times and 2.9 times, respectively, in iron overloaded HH4 cells. Our subsequent experiments detected that FAC-treated HH4 cells can activate IL6 expression through TLR2-mediated inflammatory responses via the NF-κB pathway. Conclusions: In this study, we demonstrated that iron overload induced hepatocytes triggering TLR2-mediated inflammatory response via NF-κB signaling pathway in HH4 cells. Full article

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

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12 pages, 2666 KiB

Open AccessConference Report

Treatment with Akebia Saponin D Ameliorates Aβ_1–42-Induced Memory Impairment and Neurotoxicity in Rats

by Yongde Chen, Xiaolin Yang, Tong Chen, Jing Ji, Li Lan, Rong Hu and Hui Ji

Molecules 2016, 21(3), 323; https://doi.org/10.3390/molecules21030323 - 8 Mar 2016

Cited by 7 | Viewed by 5554

Abstract

Amyloid-β peptide (Aβ) is known to be directly associated with the progressive neuronal death observed in Alzheimer’s disease (AD). However, effective neuroprotective approaches against Aβ neurotoxicity are still unavailable. In the present study, we investigated the protective effects of Akebia saponin D (ASD), [...] Read more.

Amyloid-β peptide (Aβ) is known to be directly associated with the progressive neuronal death observed in Alzheimer’s disease (AD). However, effective neuroprotective approaches against Aβ neurotoxicity are still unavailable. In the present study, we investigated the protective effects of Akebia saponin D (ASD), a typical compound isolated from the rhizome of Dipsacus asper Wall, on Aβ_1–42-induced impairment of learning and memory formation and explored the probable underlying molecular mechanisms. We found that treatment with ASD (30, 90 or 270 mg/kg) significantly ameliorated impaired spatial learning and memory in intracerebroventricularly (ICV) Aβ_1–42-injected rats, as evidenced by a decrease tendency in escape latency during acquisition trials and improvement in exploratory activities in the probe trial in Morris water maze (MWM). Further study showed that ASD reversed Aβ_1–42-induced accumulation of Aβ_1–42 and Aβ_1–40 in the hippocampus through down-regulating the expression of BACE and Presenilin 2 accompanied with increased the expression of TACE, IDE and LRP-1. Taken together, our findings suggested that ASD exerted therapeutic effects on Aβ-induced cognitive deficits via amyloidogenic pathway. Full article

(This article belongs to the Special Issue Molecules against Alzheimer)

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9 pages, 785 KiB

Open AccessArticle

New Cerebroside and Nucleoside Derivatives from a Red Sea Strain of the Marine Cyanobacterium Moorea producens

by Diaa T.A. Youssef, Sabrin R.M. Ibrahim, Lamiaa A. Shaala, Gamal A. Mohamed and Zainy M. Banjar

Molecules 2016, 21(3), 324; https://doi.org/10.3390/molecules21030324 - 9 Mar 2016

Cited by 17 | Viewed by 5961

Abstract

In the course of our ongoing efforts to identify marine-derived bioactive compounds, the marine cyanobacterium Moorea producens was investigated. The organic extract of the Red Sea cyanobacterium afforded one new cerebroside, mooreaside A (1), two new nucleoside derivatives, 3-acetyl-2′-deoxyuridine (2) and 3-phenylethyl-2′-deoxyuridine (3), [...] Read more.

In the course of our ongoing efforts to identify marine-derived bioactive compounds, the marine cyanobacterium Moorea producens was investigated. The organic extract of the Red Sea cyanobacterium afforded one new cerebroside, mooreaside A (1), two new nucleoside derivatives, 3-acetyl-2′-deoxyuridine (2) and 3-phenylethyl-2′-deoxyuridine (3), along with the previously reported compounds thymidine (4) and 2,3-dihydroxypropyl heptacosanoate (5). The structures of the compounds were determined by different spectroscopic studies (UV, IR, 1D, 2D NMR, and HRESIMS), as well as comparison with the literature data. Compounds 1–5 showed variable cytotoxic activity against three cancer cell lines. Full article

(This article belongs to the Collection Bioactive Compounds)

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10 pages, 1374 KiB

Open AccessArticle

Phosphorylation of Akt by SC79 Prevents Iron Accumulation and Ameliorates Early Brain Injury in a Model of Experimental Subarachnoid Hemorrhage

by Shuangying Hao, Chuanhui Song, Longcheng Shang, Yu Jiang, Tong Qiao and Kuanyu Li

Molecules 2016, 21(3), 325; https://doi.org/10.3390/molecules21030325 - 10 Mar 2016

Cited by 21 | Viewed by 6654 | Correction

Abstract

Previous studies have demonstrated that activation of Akt may alleviate early brain injury (EBI) following subarachnoid hemorrhage (SAH). This study is undertaken to determine whether iron metabolism is involved in the beneficial effect of Akt activation after SAH. Therefore, we used a novel [...] Read more.

Previous studies have demonstrated that activation of Akt may alleviate early brain injury (EBI) following subarachnoid hemorrhage (SAH). This study is undertaken to determine whether iron metabolism is involved in the beneficial effect of Akt activation after SAH. Therefore, we used a novel molecule, SC79, to activate Akt in an experimental Sprague–Dawley rat model of SAH. Rats were randomly divided into four groups as follows: sham, SAH, SAH + vehicle, SAH + SC79. The results confirmed that SC79 effectively enhanced the defense against oxidative stress and alleviated EBI in the temporal lobe after SAH. Interestingly, we found that phosphorylation of Akt by SC79 reduced cell surface transferrin receptor-mediated iron uptake and promoted ferroportin-mediated iron transport after SAH. As a result, SC79 administration diminished the iron content in the brain tissue. Moreover, the impaired Fe-S cluster biogenesis was recovered and loss of the activities of the Fe-S cluster-containing enzymes were regained, indicating that injured mitochondrial functions are restored to healthy levels. These findings suggest that disrupted iron homeostasis could contribute to EBI and Akt activation may regulate iron metabolism to relieve iron toxicity, further protecting neurons from EBI after SAH. Full article

(This article belongs to the Section Medicinal Chemistry)

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9 pages, 3531 KiB

Open AccessArticle

Hydrazonoyl Chlorides as Precursors for Synthesis of Novel Bis-Pyrrole Derivatives

by Nabila Abdelshafy Kheder

Molecules 2016, 21(3), 326; https://doi.org/10.3390/molecules21030326 - 9 Mar 2016

Cited by 19 | Viewed by 5605

Abstract

A convenient synthesis of some novel bis-pyrrole derivatives via hydrazonoyl halides is described. Antimicrobial evaluation of some selected examples of the synthesized products was carried out. The bis-pyrrole derivative having chloro substituents showed good activity against all of the used microbes. The molecular [...] Read more.

A convenient synthesis of some novel bis-pyrrole derivatives via hydrazonoyl halides is described. Antimicrobial evaluation of some selected examples of the synthesized products was carried out. The bis-pyrrole derivative having chloro substituents showed good activity against all of the used microbes. The molecular docking of the bis-pyrrole derivatives was performed by the Molecular Operating Environment (MOE) program. Full article

(This article belongs to the Collection Heterocyclic Compounds)

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11 pages, 1127 KiB

Open AccessArticle

A Computational Study of the Mechanism of Succinimide Formation in the Asn–His Sequence: Intramolecular Catalysis by the His Side Chain

by Ohgi Takahashi, Noriyoshi Manabe and Ryota Kirikoshi

Molecules 2016, 21(3), 327; https://doi.org/10.3390/molecules21030327 - 9 Mar 2016

Cited by 10 | Viewed by 5973

Abstract

The rates of deamidation reactions of asparagine (Asn) residues which occur spontaneously and nonenzymatically in peptides and proteins via the succinimide intermediate are known to be strongly dependent on the nature of the following residue on the carboxyl side (Xxx). The formation of [...] Read more.

The rates of deamidation reactions of asparagine (Asn) residues which occur spontaneously and nonenzymatically in peptides and proteins via the succinimide intermediate are known to be strongly dependent on the nature of the following residue on the carboxyl side (Xxx). The formation of the succinimide intermediate is by far the fastest when Xxx is glycine (Gly), the smallest amino acid residue, while extremely slow when Xxx is bulky such as isoleucine (Ile) and valine (Val). In this respect, it is very interesting to note that the succinimide formation is definitely accelerated when Xxx is histidine (His) despite its large size. In this paper, we computationally show that, in an Asn–His sequence, the His side-chain imidazole group (in the neutral Nε-protonated form) can specifically catalyze the formation of the tetrahedral intermediate in the succinimide formation by mediating a proton transfer. The calculations were performed for Ace−Asn−His−Nme (Ace = acetyl, Nme = methylamino) as a model compound by the density functional theory with the B3LYP functional and the 6-31+G(d,p) basis set. We also show that the tetrahedral intermediate, once protonated at the NH₂ group, easily releases an ammonia molecule to give the succinimide species. Full article

(This article belongs to the Special Issue Biomolecules Modification)

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19 pages, 4449 KiB

Open AccessArticle

Structure, Solubility and Stability of Orbifloxacin Crystal Forms: Hemihydrate versus Anhydrate

by Olimpia Maria Martins Santos, Jennifer Tavares Jacon Freitas, Edith Cristina Laignier Cazedey, Magali Benjamim de Araújo and Antonio Carlos Doriguetto

Molecules 2016, 21(3), 328; https://doi.org/10.3390/molecules21030328 - 9 Mar 2016

Cited by 14 | Viewed by 6652

Abstract

Orbifloxacin (ORBI) is a widely used antimicrobial drug of the fluoroquinolone class. In the official pharmaceutical compendia the existence of polymorphism in this active pharmaceutical ingredient (API) is reported. No crystal structure has been reported for this API and as described in the [...] Read more.

Orbifloxacin (ORBI) is a widely used antimicrobial drug of the fluoroquinolone class. In the official pharmaceutical compendia the existence of polymorphism in this active pharmaceutical ingredient (API) is reported. No crystal structure has been reported for this API and as described in the literature, its solubility is very controversial. Considering that different solid forms of the same API may have different physicochemical properties, these different solubilities may have resulted from analyses inadvertently carried out on different polymorphs. The solubility is the most critical property because it can affect the bioavailability and may compromise the quality of a drug product. The crystalline structure of ORBI determined by SCXRD is reported here for the first time. The structural analysis reveals that the ORBI molecule is zwitterionic and hemihydrated. ORBI hemihydrated form was characterized by the following techniques: TG/DTA, FTIR-ATR, and PXRD. A second crystalline ORBI form is also reported: the ORBI anhydrous form was obtained by heating the hemihydrate. These ORBI solid forms were isomorphous, since no significant change in unit cell and space group symmetry were observed. The solid-state phase transformation between these forms is discussed and the equilibrium solubility data were examined in order to check the impact of the differences observed in their crystalline structures. Full article

(This article belongs to the Special Issue Crystallization of Pharmaceuticals)

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10 pages, 1069 KiB

Open AccessArticle

Synthesis and Selective Cytotoxic Activities on Rhabdomyosarcoma and Noncancerous Cells of Some Heterocyclic Chalcones

by Tuong-Ha Do, Dai-Minh Nguyen, Van-Dat Truong, Thi-Hong-Tuoi Do, Minh-Tri Le, Thanh-Quan Pham, Khac-Minh Thai and Thanh-Dao Tran

Molecules 2016, 21(3), 329; https://doi.org/10.3390/molecules21030329 - 9 Mar 2016

Cited by 13 | Viewed by 7345

Abstract

Chemically diverse heterocyclic chalcones were prepared and evaluated for cytotoxicity, aiming to push forward potency and selectivity. They were tested against rhabdomyosarcoma (RMS) and noncancerous cell line (LLC-PK1). The influence of heteroaryl patterns on rings A and B was studied. Heterocycle functionalities on [...] Read more.

Chemically diverse heterocyclic chalcones were prepared and evaluated for cytotoxicity, aiming to push forward potency and selectivity. They were tested against rhabdomyosarcoma (RMS) and noncancerous cell line (LLC-PK1). The influence of heteroaryl patterns on rings A and B was studied. Heterocycle functionalities on both rings, such as phenothiazine, thiophene, furan and pyridine were evaluated. Notably, the introduction of three methoxy groups at positions 3, 4, 5 on ring B appears to be critical for cytotoxicity. The best compound, with potent and selective cytotoxicity (IC₅₀ = 12.51 μM in comparison with the value 10.84 μM of paclitaxel), contains a phenothiazine moiety on ring A and a thiophene heterocycle on ring B. Most of the potential compounds only show weak cytoxicity on the noncancerous cell line LLC-PK1. Full article

(This article belongs to the Special Issue ECSOC-19)

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35 pages, 2570 KiB

Open AccessReview

Chitosan and Its Derivatives as Highly Efficient Polymer Ligands

by Alexander Pestov and Svetlana Bratskaya

Molecules 2016, 21(3), 330; https://doi.org/10.3390/molecules21030330 - 11 Mar 2016

Cited by 114 | Viewed by 14149

Abstract

The polyfunctional nature of chitosan enables its application as a polymer ligand not only for the recovery, separation, and concentration of metal ions, but for the fabrication of a wide spectrum of functional materials. Although unmodified chitosan itself is the unique cationic polysaccharide [...] Read more.

The polyfunctional nature of chitosan enables its application as a polymer ligand not only for the recovery, separation, and concentration of metal ions, but for the fabrication of a wide spectrum of functional materials. Although unmodified chitosan itself is the unique cationic polysaccharide with very good complexing properties toward numerous metal ions, its sorption capacity and selectivity can be sufficiently increased and turned via chemical modification to meet requirements of the specific applications. In this review, which covers results of the last decade, we demonstrate how different strategies of chitosan chemical modification effect metal ions binding by O-, N-, S-, and P-containing chitosan derivatives, and which mechanisms are involved in binding of metal cation and anions by chitosan derivatives. Full article

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

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31 pages, 724 KiB

Open AccessReview

Review on a Traditional Herbal Medicine, Eurycoma longifolia Jack (Tongkat Ali): Its Traditional Uses, Chemistry, Evidence-Based Pharmacology and Toxicology

by Shaheed Ur Rehman, Kevin Choe and Hye Hyun Yoo

Molecules 2016, 21(3), 331; https://doi.org/10.3390/molecules21030331 - 10 Mar 2016

Cited by 181 | Viewed by 56236

Abstract

Eurycoma longifolia Jack (known as tongkat ali), a popular traditional herbal medicine, is a flowering plant of the family Simaroubaceae, native to Indonesia, Malaysia, Vietnam and also Cambodia, Myanmar, Laos and Thailand. E. longifolia, is one of the well-known folk medicines for [...] Read more.

Eurycoma longifolia Jack (known as tongkat ali), a popular traditional herbal medicine, is a flowering plant of the family Simaroubaceae, native to Indonesia, Malaysia, Vietnam and also Cambodia, Myanmar, Laos and Thailand. E. longifolia, is one of the well-known folk medicines for aphrodisiac effects as well as intermittent fever (malaria) in Asia. Decoctions of E. longifolia leaves are used for washing itches, while its fruits are used in curing dysentery. Its bark is mostly used as a vermifuge, while the taproots are used to treat high blood pressure, and the root bark is used for the treatment of diarrhea and fever. Mostly, the roots extract of E. longifolia are used as folk medicine for sexual dysfunction, aging, malaria, cancer, diabetes, anxiety, aches, constipation, exercise recovery, fever, increased energy, increased strength, leukemia, osteoporosis, stress, syphilis and glandular swelling. The roots are also used as an aphrodisiac, antibiotic, appetite stimulant and health supplement. The plant is reported to be rich in various classes of bioactive compounds such as quassinoids, canthin-6-one alkaloids, β-carboline alkaloids, triterpene tirucallane type, squalene derivatives and biphenyl neolignan, eurycolactone, laurycolactone, and eurycomalactone, and bioactive steroids. Among these phytoconstituents, quassinoids account for a major portion of the E. longifolia root phytochemicals. An acute toxicity study has found that the oral Lethal Dose 50 (LD₅₀) of the alcoholic extract of E. longifolia in mice is between 1500–2000 mg/kg, while the oral LD₅₀ of the aqueous extract form is more than 3000 mg/kg. Liver and renal function tests showed no adverse changes at normal daily dose and chronic use of E. longifolia. Based on established literature on health benefits of E. longifolia, it is important to focus attention on its more active constituents and the constituents’ identification, determination, further development and most importantly, the standardization. Besides the available data, more evidence is required regarding its therapeutic efficacy and safety, so it can be considered a rich herbal source of new drug candidates. It is very important to conserve this valuable medicinal plant for the health benefit of future generations. Full article

(This article belongs to the Collection Herbal Medicine Research)

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15 pages, 2260 KiB

Open AccessArticle

Investigation of the Pyridinium Ylide—Alkyne Cycloaddition as a Fluorogenic Coupling Reaction

by Simon Bonte, Ioana Otilia Ghinea, Rodica Dinica, Isabelle Baussanne and Martine Demeunynck

Molecules 2016, 21(3), 332; https://doi.org/10.3390/molecules21030332 - 10 Mar 2016

Cited by 16 | Viewed by 8522

Abstract

The cycloaddition of pyridinium ylides with alkynes was investigated under mild conditions. A series of 13 pyridinium salts was prepared by alkylation of 4-substituted pyridines. Their reactivity with propiolic ester or amide in various reaction conditions (different temperatures, solvents, added bases) was studied, [...] Read more.

The cycloaddition of pyridinium ylides with alkynes was investigated under mild conditions. A series of 13 pyridinium salts was prepared by alkylation of 4-substituted pyridines. Their reactivity with propiolic ester or amide in various reaction conditions (different temperatures, solvents, added bases) was studied, and 11 indolizines, with three points of structural variation, were, thus, isolated and characterized. The highest yields were obtained when electron-withdrawing groups were present on both the pyridinium ylide, generated in situ from the corresponding pyridinium salt, and the alkyne (X, Z = ester, amide, CN, carbonyl, etc.). Electron-withdrawing substituents, lowering the acid dissociation constant (pKa) of the pyridinium salts, allow the cycloaddition to proceed at pH 7.5 in aqueous buffers at room temperature. Full article

(This article belongs to the Collection Heterocyclic Compounds)

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12 pages, 1380 KiB

Open AccessArticle

Synthesis of New Functionalized Indoles Based on Ethyl Indol-2-carboxylate

by Ahmed T. A. Boraei, El Sayed H. El Ashry, Assem Barakat and Hazem A. Ghabbour

Molecules 2016, 21(3), 333; https://doi.org/10.3390/molecules21030333 - 10 Mar 2016

Cited by 23 | Viewed by 7766

Abstract

Successful alkylations of the nitrogen of ethyl indol-2-carboxylate were carried out using aq. KOH in acetone. The respective N-alkylated acids could be obtained without separating the N-alkylated esters by increasing the amount of KOH and water. The use of NaOMe in [...] Read more.

Successful alkylations of the nitrogen of ethyl indol-2-carboxylate were carried out using aq. KOH in acetone. The respective N-alkylated acids could be obtained without separating the N-alkylated esters by increasing the amount of KOH and water. The use of NaOMe in methanol led to transesterification instead of the alkylation, while the use of NaOEt led to low yields of the N-alkylated acids. Hydrazinolysis of the ester gave indol-2-carbohydrazide which then was allowed to react with different aromatic aldehydes and ketones in ethanol catalyzed by acetic acid. Indol-2-thiosemicarbazide was used in a heterocyclization reaction to form thiazoles. The new structures were confirmed using NMR, mass spectrometry and X-ray single crystal analysis. Full article

(This article belongs to the Section Organic Chemistry)

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18 pages, 6455 KiB

Open AccessArticle

Quercetin-Rich Guava (Psidium guajava) Juice in Combination with Trehalose Reduces Autophagy, Apoptosis and Pyroptosis Formation in the Kidney and Pancreas of Type II Diabetic Rats

by Chia-Fa Lin, Yen-Ting Kuo, Tsung-Ying Chen and Chiang-Ting Chien

Molecules 2016, 21(3), 334; https://doi.org/10.3390/molecules21030334 - 10 Mar 2016

Cited by 77 | Viewed by 10637

Abstract

We explored whether the combination of anti-oxidant and anti-inflammatory guava (Psidium guajava) and trehalose treatment protects the kidney and pancreas against Type II diabetes (T2DM)-induced injury in rats. We measured the active component of guava juice by HPLC analysis. T2DM was [...] Read more.

We explored whether the combination of anti-oxidant and anti-inflammatory guava (Psidium guajava) and trehalose treatment protects the kidney and pancreas against Type II diabetes (T2DM)-induced injury in rats. We measured the active component of guava juice by HPLC analysis. T2DM was induced in Wistar rats by intraperitoneal administration of nicotinamide and streptozotocin and combination with high fructose diets for 8 weeks. The rats fed with different dosages of guava juice in combination with or without trehalose for 4 weeks were evaluated the parameters including OGTT, plasma insulin, HbA1c, HOMA-IR (insulin resistance) and HOMA-β (β cell function and insulin secretion). We measured oxidative and inflammatory degrees by immunohistochemistry stain, fluorescent stain, and western blot and serum and kidney reactive oxygen species (ROS) by a chemiluminescence analyzer. High content of quercetin in the guava juice scavenged H₂O₂ and HOCl, whereas trehalose selectively reduced H₂O₂, not HOCl. T2DM affected the levels in OGTT, plasma insulin, HbA1c, HOMA-IR and HOMA-β, whereas these T2DM-altered parameters, except HbA1c, were significantly improved by guava and trehalose treatment. The levels of T2DM-enhanced renal ROS, 4-hydroxynonenal, caspase-3/apoptosis, LC3-B/autophagy and IL-1β/pyroptosis were significantly decreased by guava juice and trehalose. The combination with trehalose and guava juice protects the pancreas and kidney against T2DM-induced injury. Full article

(This article belongs to the Section Medicinal Chemistry)

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16 pages, 3255 KiB

Open AccessArticle

Functionalization of a Triazine Dendrimer Presenting Four Maleimides on the Periphery and a DOTA Group at the Core

by Changsuk Lee, Kun Ji and Eric E. Simanek

Molecules 2016, 21(3), 335; https://doi.org/10.3390/molecules21030335 - 10 Mar 2016

Cited by 10 | Viewed by 6266

Abstract

A readily and rapidly accessible triazine dendrimer was manipulated in four steps with 23% overall yield to give a construct displaying four maleimide groups and DOTA. The maleimide groups of the dendrimer are sensitive to hydrolysis under basic conditions. The addition of up [...] Read more.

A readily and rapidly accessible triazine dendrimer was manipulated in four steps with 23% overall yield to give a construct displaying four maleimide groups and DOTA. The maleimide groups of the dendrimer are sensitive to hydrolysis under basic conditions. The addition of up to four molecules of water can be observed via mass spectrometry and HPLC. The evolution in the alkene region of the ¹H-NMR—the transformation of the maleimide singlet to the appearance of two doublets—is consistent with imide hydrolysis and not the Michael addition. The hydrolysis events that proceeded over hours are sufficiently slower than the desired thiol addition reactions that occur in minutes. The addition of thiols to maleimides can be accomplished in a variety of solvents. The thiols examined derived from cysteine and include the protected amino acid, a protected dipeptide, and native oligopeptides containing either 9 or 18 amino acids. The addition reactions were monitored with HPLC and mass spectrometry in most cases. Complete substitution was observed for small molecule reactants. The model peptides containing nine or eighteen amino acids provided a mixture of products averaging between 3 and 4 substitutions/dendrimer. The functionalization of the chelate group with gadolinium was also accomplished easily. Full article

(This article belongs to the Special Issue Functional Dendrimers)

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5 pages, 763 KiB

Open AccessArticle

New Anti-HBV C-Boivinopyranosyl Flavones from Alternanthera philoxeroides

by Bin Li, Qing-Lan Guo, Ying Tian, Shi-Jun Liu, Qiong Wang, Li Chen and Jun-Xing Dong

Molecules 2016, 21(3), 336; https://doi.org/10.3390/molecules21030336 - 14 Mar 2016

Cited by 15 | Viewed by 5656

Abstract

C-boivinopyranosyl flavones have rarely been isolated from nature. In the search for anti-HBV (hepatitis b virus) constituents of Alternanthera philoxeroides, two new compounds, luteolin-6-C-β-d-boivinopyranosyl-3′-O-β-d-glucopyranoside (1) and chrysoeriol-6-C-β-d-boivinopyranosyl-4′-O-β- [...] Read more.

C-boivinopyranosyl flavones have rarely been isolated from nature. In the search for anti-HBV (hepatitis b virus) constituents of Alternanthera philoxeroides, two new compounds, luteolin-6-C-β-d-boivinopyranosyl-3′-O-β-d-glucopyranoside (1) and chrysoeriol-6-C-β-d-boivinopyranosyl-4′-O-β-d-glucopyranoside (2), along with three known C-boivinopyranosyl flavones (compounds 3–5) were isolated. Their structures were determined by spectroscopic analyses including 1D and 2D NMR, HR-ESI-MS, IR spectra. Compounds 1, 2 and 3 showed significant anti-HBV activities through specifically inhibiting the secretion of HBsAg in HepG2.2.15. Full article

(This article belongs to the Collection Bioactive Compounds)

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12 pages, 396 KiB

Open AccessReview

Role of Intestinal Microbiota in Baicalin-Induced Drug Interaction and Its Pharmacokinetics

by Keumhan Noh, Youra Kang, Mahesh Raj Nepal, Ki Sun Jeong, Do Gyeong Oh, Mi Jeong Kang, Sangkyu Lee, Wonku Kang, Hye Gwang Jeong and Tae Cheon Jeong

Molecules 2016, 21(3), 337; https://doi.org/10.3390/molecules21030337 - 10 Mar 2016

Cited by 88 | Viewed by 11524

Abstract

Since many glycoside compounds in natural products are hydrolyzed by intestinal microbiota when administered orally, it is of interest to know whether their pharmacological effects are derived from the glycoside itself or from the aglycone form in vivo. An interesting example is [...] Read more.

Since many glycoside compounds in natural products are hydrolyzed by intestinal microbiota when administered orally, it is of interest to know whether their pharmacological effects are derived from the glycoside itself or from the aglycone form in vivo. An interesting example is baicalin versus baicalein, the aglycone of baicalin, which is contained in some herbs from Labiatae including Scutellaria baicalensis Georgi and Scutellaria lateriflora Linne. The herbs have been extensively used for treatment of inflammatory diseases in Asia. Although there have been numerous reports regarding the pharmacological effects of baicalin and baicalein in vivo and in vitro, some reports indicated that the glycoside form would hardly be absorbed in the intestine and that it should be hydrolyzed to baicalein in advance for absorption. Therefore, the role of metabolism by intestinal microbiota should also be considered in the metabolism of baicalin. In addition, baicalin contains a glucuronide moiety in its structure, by which baicalin and baicalein show complex pharmacokinetic behaviors, due to the interconversion between them by phase II enzymes in the body. Recently, concerns about drug interaction with baicalin and/or baicalein have been raised, because of the co-administration of Scutellaria species with certain drugs. Herein, we reviewed the role of intestinal microbiota in pharmacokinetic characteristics of baicalin and baicalein, with regards to their pharmacological and toxicological effects. Full article

(This article belongs to the Collection Herbal Medicine Research)

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12 pages, 604 KiB

Open AccessReview

Recent Advances in Volatiles of Teas

by Xin-Qiang Zheng, Qing-Sheng Li, Li-Ping Xiang and Yue-Rong Liang

Molecules 2016, 21(3), 338; https://doi.org/10.3390/molecules21030338 - 11 Mar 2016

Cited by 219 | Viewed by 11453

Abstract

Volatile compounds are important components of tea aroma, a key attribute of sensory quality. The present review examines the formation of aromatic volatiles of various kinds of teas and factors influencing the formation of tea volatiles, including tea cultivar, growing environment and agronomic [...] Read more.

Volatile compounds are important components of tea aroma, a key attribute of sensory quality. The present review examines the formation of aromatic volatiles of various kinds of teas and factors influencing the formation of tea volatiles, including tea cultivar, growing environment and agronomic practices, processing method and storage of tea. The determination of tea volatiles and the relationship of active-aroma volatiles with the sensory qualities of tea are also discussed in the present paper. Full article

(This article belongs to the Collection Recent Advances in Flavors and Fragrances)

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13 pages, 1658 KiB

Open AccessArticle

A Peptoid-Based Fluorescent Sensor for Cyanide Detection

by Bumhee Lim and Jeeyeon Lee

Molecules 2016, 21(3), 339; https://doi.org/10.3390/molecules21030339 - 10 Mar 2016

Cited by 27 | Viewed by 7850

Abstract

Peptoids, N-substituted glycine oligomers, are versatile peptidomimetics with diverse biomedical applications. However, strategies to the development of novel fluorescent peptoids as chemical sensors have not been extensively explored, yet. Here, we synthesized a novel peptoid-based fluorescent probe in which a coumarin moiety [...] Read more.

Peptoids, N-substituted glycine oligomers, are versatile peptidomimetics with diverse biomedical applications. However, strategies to the development of novel fluorescent peptoids as chemical sensors have not been extensively explored, yet. Here, we synthesized a novel peptoid-based fluorescent probe in which a coumarin moiety was incorporated via copper(I)-catalyzed azide-alkyne cycloaddition reaction. Fluorescence of the newly generated coumarin-peptoid was dramatically quenched upon coordination of the Cu²⁺ ion, and the resulting peptoid-Cu²⁺ complex exhibited significant Turn-ON fluorescence following the addition of CN⁻. The rapid and reversible response, combined with cyanide selectivity of the synthesized peptoid, reflects a multistep photo-process and supports its utility as a new type of CN⁻ sensor. Full article

(This article belongs to the Special Issue Photoactive Molecules)

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15 pages, 464 KiB

Open AccessArticle

Design, Synthesis and Antibacterial Evaluation of Some New 2-Phenyl-quinoline-4-carboxylic Acid Derivatives

by Xiaoqin Wang, Xiaoyang Xie, Yuanhong Cai, Xiaolan Yang, Jiayu Li, Yinghan Li, Wenna Chen and Minghua He

Molecules 2016, 21(3), 340; https://doi.org/10.3390/molecules21030340 - 10 Mar 2016

Cited by 44 | Viewed by 9631

Abstract

A series of new 2-phenyl-quinoline-4-carboxylic acid derivatives was synthesized starting from aniline, 2-nitrobenzaldehyde, pyruvic acid followed by Doebner reaction, amidation, reduction, acylation and amination. All of the newly-synthesized compounds were characterized by ¹H-NMR, ¹³C-NMR and HRMS. The antibacterial activities of these [...] Read more.

A series of new 2-phenyl-quinoline-4-carboxylic acid derivatives was synthesized starting from aniline, 2-nitrobenzaldehyde, pyruvic acid followed by Doebner reaction, amidation, reduction, acylation and amination. All of the newly-synthesized compounds were characterized by ¹H-NMR, ¹³C-NMR and HRMS. The antibacterial activities of these compounds against Gram-negative (Escherichia coli, Pseudomonas aeruginosa) and Gram-positive bacteria (Staphylococcus aureus, Bacillus subtilis), as well as one strain of methicillin-resistant Staphylococcus aureus (MRSA) bacteria were evaluated by the agar diffusion method (zone of inhibition) and a broth dilution method (minimum inhibitory concentration (MIC)), and their structure-activity relationships were obtained and discussed. The results revealed that some compounds displayed good antibacterial activity against Staphylococcus aureus, and Compounds 5a₄ and 5a₇ showed the best inhibition with an MIC value of 64 μg/mL against Staphylococcus aureus and with an MIC value of 128 μg/mL against Escherichia coli, respectively. The results of the MTT assay illustrated the low cytotoxicity of Compound 5a₄. Full article

(This article belongs to the Section Medicinal Chemistry)

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3 pages, 154 KiB

Open AccessEditorial

Coumarins, Xanthones and Related Compounds

by Pascal Richomme

Molecules 2016, 21(3), 341; https://doi.org/10.3390/molecules21030341 - 10 Mar 2016

Cited by 4 | Viewed by 6196

Abstract

It has long been known that coumarins (γ-pyrones) and xanthones (α-pyrones) together form a large class of naturally occurring compounds exhibiting a wide range of biological activities.[...] Full article

(This article belongs to the Special Issue Coumarins, Xanthones and Related Compounds)

18 pages, 877 KiB

Open AccessReview

Nanotechnology-Based Drug Delivery Systems for Photodynamic Therapy of Cancer: A Review

by Giovana Maria Fioramonti Calixto, Jéssica Bernegossi, Laura Marise De Freitas, Carla Raquel Fontana and Marlus Chorilli

Molecules 2016, 21(3), 342; https://doi.org/10.3390/molecules21030342 - 11 Mar 2016

Cited by 433 | Viewed by 28521

Abstract

Photodynamic therapy (PDT) is a promising alternative approach for improved cancer treatment. In PDT, a photosensitizer (PS) is administered that can be activated by light of a specific wavelength, which causes selective damage to the tumor and its surrounding vasculature. The success of [...] Read more.

Photodynamic therapy (PDT) is a promising alternative approach for improved cancer treatment. In PDT, a photosensitizer (PS) is administered that can be activated by light of a specific wavelength, which causes selective damage to the tumor and its surrounding vasculature. The success of PDT is limited by the difficulty in administering photosensitizers (PSs) with low water solubility, which compromises the clinical use of several molecules. Incorporation of PSs in nanostructured drug delivery systems, such as polymeric nanoparticles (PNPs), solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), gold nanoparticles (AuNPs), hydrogels, liposomes, liquid crystals, dendrimers, and cyclodextrin is a potential strategy to overcome this difficulty. Additionally, nanotechnology-based drug delivery systems may improve the transcytosis of a PS across epithelial and endothelial barriers and afford the simultaneous co-delivery of two or more drugs. Based on this, the application of nanotechnology in medicine may offer numerous exciting possibilities in cancer treatment and improve the efficacy of available therapeutics. Therefore, the aim of this paper is to review nanotechnology-based drug delivery systems for photodynamic therapy of cancer. Full article

(This article belongs to the Special Issue Pharmaceutical Nanotechnology: Novel Approaches)

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16 pages, 1678 KiB

Open AccessArticle

Genetic and Epigenetic Approaches for the Possible Detection of Adulteration and Auto-Adulteration in Saffron (Crocus sativus L.) Spice

by Giovanna Soffritti, Matteo Busconi, Rosa Ana Sánchez, Jean-Marie Thiercelin, Moschos Polissiou, Marta Roldán and José Antonio Fernández

Molecules 2016, 21(3), 343; https://doi.org/10.3390/molecules21030343 - 11 Mar 2016

Cited by 55 | Viewed by 9292

Abstract

Saffron (Crocus sativus L.) is very expensive and, because of this, often subject to adulteration. Modern genetic fingerprinting techniques are an alternative low cost technology to the existing chemical techniques, which are used to control the purity of food products. Buddleja officinalis [...] Read more.

Saffron (Crocus sativus L.) is very expensive and, because of this, often subject to adulteration. Modern genetic fingerprinting techniques are an alternative low cost technology to the existing chemical techniques, which are used to control the purity of food products. Buddleja officinalis Maxim, Gardenia jasminoides Ellis, Curcuma longa L., Carthamus tinctorius L. and Calendula officinalis L. are among the most frequently-used adulterants in saffron spice. Three commercial kits were compared concerning the ability to recover PCR-grade DNA from saffron, truly adulterated samples and possible adulterants, with a clear difference among them, mainly with the processed samples. Only one of the three kits was able to obtain amplifiable DNA from almost all of the samples, with the exception of extracts. On the recovered DNA, new markers were developed based on the sequence of the plastid genes matK and rbcL. These primers, mainly those developed on matK, were able to recognize saffron and the adulterant species and also in mixtures with very low percentages of adulterant. Finally, considering that the addition of different parts of saffron flowers is one of the most widespread adulterations, by analyzing the DNA of the different parts of the flower (styles, stamens and tepals) at the genetic and epigenetic level, we succeeded in finding differences between the three tissues that can be further evaluated for a possible detection of the kind of fraud. Full article

(This article belongs to the Special Issue Saffron (Crocus sativus, L.): Omics and Other Techniques in Authenticity, Quality and Bioactivity Studies)

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18 pages, 528 KiB

Open AccessReview

Regulation of Obesity and Metabolic Complications by Gamma and Delta Tocotrienols

by Lu Zhao, Xiefan Fang, Maurice R. Marshall and Soonkyu Chung

Molecules 2016, 21(3), 344; https://doi.org/10.3390/molecules21030344 - 11 Mar 2016

Cited by 38 | Viewed by 9674

Abstract

Tocotrienols (T3s) are a subclass of unsaturated vitamin E that have been extensively studied for their anti-proliferative, anti-oxidative and anti-inflammatory properties in numerous cancer studies. Recently, T3s have received increasing attention due to their previously unrecognized property to attenuate obesity and its associated [...] Read more.

Tocotrienols (T3s) are a subclass of unsaturated vitamin E that have been extensively studied for their anti-proliferative, anti-oxidative and anti-inflammatory properties in numerous cancer studies. Recently, T3s have received increasing attention due to their previously unrecognized property to attenuate obesity and its associated metabolic complications. In this review, we comprehensively evaluated the recent published scientific literature about the influence of T3s on obesity, with a particular emphasis on the signaling pathways involved. T3s have been demonstrated in animal models or human subjects to reduce fat mass, body weight, plasma concentrations of free fatty acid, triglycerides and cholesterol, as well as to improve glucose and insulin tolerance. Their mechanisms of action in adipose tissue mainly include (1) modulation of fat cell adipogenesis and differentiation; (2) modulation of energy sensing; (3) induction of apoptosis in preadipocytes and (4) modulation of inflammation. Studies have also been conducted to investigate the effects of T3s on other targets, e.g., the immune system, liver, muscle, pancreas and bone. Since δT3 and γT3 are regarded as the most active isomers among T3s, their clinical relevance to reduce obesity should be investigated in human trials. Full article

(This article belongs to the Special Issue Natural Products in Anti-Obesity Therapy)

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14 pages, 2125 KiB

Open AccessArticle

Use of a Ceramic Membrane to Improve the Performance of Two-Separate-Phase Biocatalytic Membrane Reactor

by Giuseppe Ranieri, Rosalinda Mazzei, Zhentao Wu, Kang Li and Lidietta Giorno

Molecules 2016, 21(3), 345; https://doi.org/10.3390/molecules21030345 - 14 Mar 2016

Cited by 26 | Viewed by 6340

Abstract

Biocatalytic membrane reactors (BMR) combining reaction and separation within the same unit have many advantages over conventional reactor designs. Ceramic membranes are an attractive alternative to polymeric membranes in membrane biotechnology due to their high chemical, thermal and mechanical resistance. Another important use [...] Read more.

Biocatalytic membrane reactors (BMR) combining reaction and separation within the same unit have many advantages over conventional reactor designs. Ceramic membranes are an attractive alternative to polymeric membranes in membrane biotechnology due to their high chemical, thermal and mechanical resistance. Another important use is their potential application in a biphasic membrane system, where support solvent resistance is highly needed. In this work, the preparation of asymmetric ceramic hollow fibre membranes and their use in a two-separate-phase biocatalytic membrane reactor will be described. The asymmetric ceramic hollow fibre membranes were prepared using a combined phase inversion and sintering technique. The prepared fibres were then used as support for lipase covalent immobilization in order to develop a two-separate-phase biocatalytic membrane reactor. A functionalization method was proposed in order to increase the density of the reactive hydroxyl groups on the surface of ceramic membranes, which were then amino-activated and treated with a crosslinker. The performance and the stability of the immobilized lipase were investigated as a function of the amount of the immobilized biocatalytst. Results showed that it is possible to immobilize lipase on a ceramic membrane without altering its catalytic performance (initial residual specific activity 93%), which remains constant after 6 reaction cycles. Full article

(This article belongs to the Special Issue Membrane Catalysis)

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24 pages, 3290 KiB

Open AccessArticle

Nanopore Event-Transduction Signal Stabilization for Wide pH Range under Extreme Chaotrope Conditions

by Stephen Winters-Hilt and Alexander Stoyanov

Molecules 2016, 21(3), 346; https://doi.org/10.3390/molecules21030346 - 14 Mar 2016

Cited by 2 | Viewed by 4949

Abstract

Operation of an α-hemolysin nanopore transduction detector is found to be surprisingly robust over a critical range of pH (6–9), including physiological pH = 7.4 and polymerase chain reaction (PCR) pH = 8.4, and extreme chaotrope concentration, including 5 M urea. The engineered [...] Read more.

Operation of an α-hemolysin nanopore transduction detector is found to be surprisingly robust over a critical range of pH (6–9), including physiological pH = 7.4 and polymerase chain reaction (PCR) pH = 8.4, and extreme chaotrope concentration, including 5 M urea. The engineered transducer molecule that is captured in the standard α-hemolysin nanopore detector, to transform it into a transduction detector, appears to play a central role in this stabilization process by stabilizing the channel against gating during its capture. This enables the nanopore transduction detector to operate as a single molecule “nanoscope” in a wide range of conditions, where tracking on molecular state is possible in a variety of different environmental conditions. In the case of streptavidin biosensing, results are shown for detector operation when in the presence of extreme (5 M) urea concentration. Complications involving degenerate states are encountered at higher chaotrope concentrations, but since the degeneracy is only of order two, this is easily absorbed into the classification task as in prior work. This allows useful detector operation over a wide range of conditions relevant to biochemistry, biomedical engineering, and biotechnology. Full article

(This article belongs to the Special Issue Chemoinformatics)

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1 pages, 140 KiB

Open AccessErratum

Erratum: Li, Y., et al. Mechanism of NO Photocatalytic Oxidation on g-C₃N₄ Was Changed by Pd-QDs Modification. Molecules, 2016, 21, 36

by Molecules Editorial Office

Molecules 2016, 21(3), 347; https://doi.org/10.3390/molecules21030347 - 11 Mar 2016

Viewed by 3447

Abstract

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

(This article belongs to the Section Organic Chemistry)

6 pages, 651 KiB

Open AccessCommunication

Potential Health Risks Posed by Plant-Derived Cumulative Neurotoxic Bufadienolides in South Africa

by Christo Botha

Molecules 2016, 21(3), 348; https://doi.org/10.3390/molecules21030348 - 16 Mar 2016

Cited by 14 | Viewed by 9351

Abstract

Bufadienolide-type cardiac glycosides have a worldwide distribution and are mainly synthesized by plants, but there are also animal sources. In South Africa, members of three genera of the Crassulaceae (Cotyledon, Tylecodon and Kalanchoe) cause a unique chronic form of cardiac [...] Read more.

Bufadienolide-type cardiac glycosides have a worldwide distribution and are mainly synthesized by plants, but there are also animal sources. In South Africa, members of three genera of the Crassulaceae (Cotyledon, Tylecodon and Kalanchoe) cause a unique chronic form of cardiac glycoside poisoning, predominantly in small stock. This paretic/paralytic condition is referred to as “krimpsiekte”, cotyledonosis or “nenta”. “Krimpsiekte” is a plant poisoning only reported from South Africa and is regarded as the most important plant poisoning of small stock in the semi-arid Little Karoo and southern fringes of the Great Karoo. The toxicosis is caused by cumulative bufadienolides which have neurotoxic properties. Four types of cumulative neurotoxic bufadienolides, namely cotyledoside, and the tyledosides, orbicusides and lanceotoxins, have been isolated. Based on the structure activity relationships and certain toxicokinetic parameters possible reasons for their accumulation are presented. Consumption of edible tissues from animals that have ingested these plants poses a potential risk to humans. Full article

(This article belongs to the Special Issue Natural Toxins)

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5 pages, 340 KiB

Open AccessArticle

A New Indole Alkaloid from the Toad Venom of Bufo bufo gargarizans

by Ying-Hui Dai, Bo Shen, Ming-Yu Xia, An-Dong Wang, Yu-Lin Chen, Dong-Chun Liu and Dong Wang

Molecules 2016, 21(3), 349; https://doi.org/10.3390/molecules21030349 - 16 Mar 2016

Cited by 18 | Viewed by 5790

Abstract

A new indole alkaloid named bufobutarginine (1), along with three known bufotenines, namely, serotonin (2), bufotenidine (3), and bufotenine (4), were isolated from the water extract of toad venom. Their structures were elucidated by spectral methods. This is the first time that arginine [...] Read more.

A new indole alkaloid named bufobutarginine (1), along with three known bufotenines, namely, serotonin (2), bufotenidine (3), and bufotenine (4), were isolated from the water extract of toad venom. Their structures were elucidated by spectral methods. This is the first time that arginine has been found to be involved in the biosynthesis of bufotenines in parotid of toad. The cytotoxic activities of these compounds have been assayed against A375 and A549 cell lines by the MTT method; however, they showed no cytotoxic activities. Full article

(This article belongs to the Section Natural Products Chemistry)

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12 pages, 3438 KiB

Open AccessArticle

Solid-Phase Synthesis of Amine/Carboxyl Substituted Prolines and Proline Homologues: Scope and Limitations

by Ziniu Zhou, William L. Scott and Martin J. O’Donnell

Molecules 2016, 21(3), 350; https://doi.org/10.3390/molecules21030350 - 15 Mar 2016

Viewed by 5713

Abstract

A solid-phase procedure is used to synthesize racemic peptidomimetics based on the fundamental peptide unit. The peptidomimetics are constructed around proline or proline homologues variably substituted at the amine and carbonyl sites. The procedure expands the diversity of substituted peptidomimetic molecules available to [...] Read more.

A solid-phase procedure is used to synthesize racemic peptidomimetics based on the fundamental peptide unit. The peptidomimetics are constructed around proline or proline homologues variably substituted at the amine and carbonyl sites. The procedure expands the diversity of substituted peptidomimetic molecules available to the Distributed Drug Discovery (D3) project. Using a BAL-based solid-phase synthetic sequence the proline or proline homologue subunit is both constructed and incorporated into the peptidomimetic by an α-alkylation, hydrolysis and intramolecular cyclization sequence. Further transformations on solid-phase provide access to a variety of piperazine derivatives representing a class of molecules known to exhibit central nervous system activity. The procedure works well with proline cores, but with larger six- and seven-membered ring homologues the nature of the carboxylic acid acylating the cyclic amine can lead to side reactions and result in poor overall yields. Full article

(This article belongs to the Section Organic Chemistry)

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13 pages, 7066 KiB

Open AccessArticle

Improved Homology Model of the Human all-trans Retinoic Acid Metabolizing Enzyme CYP26A1

by Mohamed K. A. Awadalla, Thamir M. Alshammari, Leif A. Eriksson and Patricia Saenz-Méndez

Molecules 2016, 21(3), 351; https://doi.org/10.3390/molecules21030351 - 15 Mar 2016

Cited by 4 | Viewed by 7190

Abstract

A new CYP26A1 homology model was built based on the crystal structure of cyanobacterial CYP120A1. The model quality was examined for stereochemical accuracy, folding reliability, and absolute quality using a variety of different bioinformatics tools. Furthermore, the docking capabilities of the model were [...] Read more.

A new CYP26A1 homology model was built based on the crystal structure of cyanobacterial CYP120A1. The model quality was examined for stereochemical accuracy, folding reliability, and absolute quality using a variety of different bioinformatics tools. Furthermore, the docking capabilities of the model were assessed by docking of the natural substrate all-trans-retinoic acid (atRA), and a group of known azole- and tetralone-based CYP26A1 inhibitors. The preferred binding pose of atRA suggests the (4S)-OH-atRA metabolite production, in agreement with recently available experimental data. The distances between the ligands and the heme group iron of the enzyme are in agreement with corresponding distances obtained for substrates and azole inhibitors for other cytochrome systems. The calculated theoretical binding energies agree with recently reported experimental data and show that the model is capable of discriminating between natural substrate, strong inhibitors (R116010 and R115866), and weak inhibitors (liarozole, fluconazole, tetralone derivatives). Full article

(This article belongs to the Special Issue Computational Design: A New Approach to Drug and Molecular Discovery)

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21 pages, 7253 KiB

Open AccessReview

Azidation in the Difunctionalization of Olefins

by Kai Wu, Yujie Liang and Ning Jiao

Molecules 2016, 21(3), 352; https://doi.org/10.3390/molecules21030352 - 16 Mar 2016

Cited by 115 | Viewed by 12133

Abstract

Organic azides are key motifs in compounds of relevance to chemical biology, medicinal chemistry and materials science. In addition, they also serve as useful building blocks due to their remarkable reactivity. Therefore, the development of efficient protocols to synthesize these compounds is of [...] Read more.

Organic azides are key motifs in compounds of relevance to chemical biology, medicinal chemistry and materials science. In addition, they also serve as useful building blocks due to their remarkable reactivity. Therefore, the development of efficient protocols to synthesize these compounds is of great significance. This paper reviews the major applications and development of azidation in difunctionalization of olefins using azide reagents. Full article

(This article belongs to the Special Issue Organic Azides)

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19 pages, 3411 KiB

Open AccessArticle

Experimental Investigation and Simplistic Geochemical Modeling of CO₂ Mineral Carbonation Using the Mount Tawai Peridotite

by Omeid Rahmani, James Highfield, Radzuan Junin, Mark Tyrer and Amin Beiranvand Pour

Molecules 2016, 21(3), 353; https://doi.org/10.3390/molecules21030353 - 16 Mar 2016

Cited by 26 | Viewed by 6863 | Correction

Abstract

In this work, the potential of CO₂ mineral carbonation of brucite (Mg(OH)₂) derived from the Mount Tawai peridotite (forsterite based (Mg)₂SiO₄) to produce thermodynamically stable magnesium carbonate (MgCO₃) was evaluated. The effect of three [...] Read more.

In this work, the potential of CO₂ mineral carbonation of brucite (Mg(OH)₂) derived from the Mount Tawai peridotite (forsterite based (Mg)₂SiO₄) to produce thermodynamically stable magnesium carbonate (MgCO₃) was evaluated. The effect of three main factors (reaction temperature, particle size, and water vapor) were investigated in a sequence of experiments consisting of aqueous acid leaching, evaporation to dryness of the slurry mass, and then gas-solid carbonation under pressurized CO₂. The maximum amount of Mg converted to MgCO₃ is ~99%, which occurred at temperatures between 150 and 175 °C. It was also found that the reduction of particle size range from >200 to <75 µm enhanced the leaching rate significantly. In addition, the results showed the essential role of water vapor in promoting effective carbonation. By increasing water vapor concentration from 5 to 10 vol %, the mineral carbonation rate increased by 30%. This work has also numerically modeled the process by which CO₂ gas may be sequestered, by reaction with forsterite in the presence of moisture. In both experimental analysis and geochemical modeling, the results showed that the reaction is favored and of high yield; going almost to completion (within about one year) with the bulk of the carbon partitioning into magnesite and that very little remains in solution. Full article

(This article belongs to the Section Molecular Diversity)

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10 pages, 1521 KiB

Open AccessArticle

Aromatic Constituents from the Stems of Astragalus membranaceus (Fisch.) Bge. var. Mongholicus (Bge.) Hsiao

by Jia Hao, Jian Li, Xiaoxia Li, Yanxia Liu, Jingya Ruan, Yongzhe Dong, Yi Zhang and Tao Wang

Molecules 2016, 21(3), 354; https://doi.org/10.3390/molecules21030354 - 16 Mar 2016

Cited by 16 | Viewed by 5614

Abstract

Four new aromatic constituents, astraflavonoids A (1), B (2), C (3), and astramemoside A (4), along with sixteen known ones 5–20 were obtained from the stems of A. membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao. Their structures were elucidated by chemical and [...] Read more.

Four new aromatic constituents, astraflavonoids A (1), B (2), C (3), and astramemoside A (4), along with sixteen known ones 5–20 were obtained from the stems of A. membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao. Their structures were elucidated by chemical and spectroscopic methods. Among the known isolates, 14 was obtained from the Astragalus genus for the first time, while 7–12, 18–20 were isolated from the species for the first time. The effects of the compounds obtained from the plant on glucose consumption were analyzed in differentiated L6 myotubes in vitro, whereby compounds 1, 2, 3, 7, 8, 10, 11, 14, 15 and 18 displayed significant promoting effects on glucose consumption in L6 myotubes. Among them, the activities of 1, 2 and 7 were comparable to that of insulin, which suggested that these compounds may be involved in glucose metabolism and transport. Full article

(This article belongs to the Section Natural Products Chemistry)

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17 pages, 2625 KiB

Open AccessArticle

Synthesis, Characterization, and Antifungal Activity of Phenylpyrrole-Substituted Tetramic Acids Bearing Carbonates

by Wen-Qin Xu, Min Chen, Kun-Yao Wang, Zheng-Jiao Ren, Ai-Min Lu and Chun-Long Yang

Molecules 2016, 21(3), 355; https://doi.org/10.3390/molecules21030355 - 21 Mar 2016

Cited by 14 | Viewed by 5559

Abstract

For the aim of discovering new fungicide, a series of phenylpyrrole-substituted tetramic acid derivatives bearing carbonates 6a–q were designed and synthesized via 4-(2,4-dioxopyrrolidin-3-ylidene)-4-(phenylamino)butanoic acids 4a–k and the cyclized products 1′,3,4,5′-tetrahydro-[2,3′-bipyrrolylidene]-2′,4′,5(1H)-triones 5a–k. The compounds were characterized using IR, ¹H- and ¹³ [...] Read more.

For the aim of discovering new fungicide, a series of phenylpyrrole-substituted tetramic acid derivatives bearing carbonates 6a–q were designed and synthesized via 4-(2,4-dioxopyrrolidin-3-ylidene)-4-(phenylamino)butanoic acids 4a–k and the cyclized products 1′,3,4,5′-tetrahydro-[2,3′-bipyrrolylidene]-2′,4′,5(1H)-triones 5a–k. The compounds were characterized using IR, ¹H- and ¹³C-NMR spectroscopy, mass spectrometry (EI-MS), and elemental analysis. The structure of 6b was confirmed by X-ray diffraction crystallography. The title compounds 6a–q were bioassayed in vitro against the phytopathogenic fungi Fusarium graminearum, Botrytis cinerea and Rhizoctonia solani at a concentration of 100 μg/mL, respectively. Most compounds displayed good inhibitory activity. Full article

(This article belongs to the Section Organic Chemistry)

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14 pages, 3282 KiB

Open AccessArticle

Isoquercitrin Inhibits Hydrogen Peroxide-Induced Apoptosis of EA.hy926 Cells via the PI3K/Akt/GSK3β Signaling Pathway

by Meixia Zhu, Jiankuan Li, Ke Wang, Xuliang Hao, Rui Ge and Qingshan Li

Molecules 2016, 21(3), 356; https://doi.org/10.3390/molecules21030356 - 21 Mar 2016

Cited by 49 | Viewed by 8743

Abstract

Oxidative stress plays a critical role in endothelial injury and the pathogenesis of diverse cardiovascular diseases, including atherosclerosis. Isoquercitrin (quercetin-3-glucoside), a flavonoid distributed widely in plants, exhibits many biological activities, including anti-allergic, anti-viral, anti-inflammatory, and anti-oxidative effects. In the present study, the inhibitory [...] Read more.

Oxidative stress plays a critical role in endothelial injury and the pathogenesis of diverse cardiovascular diseases, including atherosclerosis. Isoquercitrin (quercetin-3-glucoside), a flavonoid distributed widely in plants, exhibits many biological activities, including anti-allergic, anti-viral, anti-inflammatory, and anti-oxidative effects. In the present study, the inhibitory effect of isoquercitrin on H₂O₂-induced apoptosis of EA.hy926 cells was evaluated. MTT assays showed that isoquercitrin significantly inhibited H₂O₂-induced loss of viability in EA.hy926 cells. Hoechst33342/PI and Annexin V-FITC/PI fluorescent double staining indicated that isoquercitrin inhibited H₂O₂-induced apoptosis of EA.hy926 cells. Western blotting demonstrated that isoquercitrin prevented H₂O₂-induced increases in cleaved caspase-9 and cleaved caspase-3 expression, while increasing expression of anti-apoptotic protein Mcl-1. Additionally, isoquercitrin significantly increased the expression of p-Akt and p-GSK3β in a dose-dependent manner in EA.hy926 cells. LY294002, a PI3K/Akt inhibitor, inhibited isoquercitrin-induced GSK3β phosphorylation and increase of Mcl-1 expression, which indicated that regulation of isoquercitrin on Mcl-1 expression was likely related to the modulation of Akt activation. These results demonstrated that the anti-apoptotic effect of isoquercitrin on H₂O₂-induced EA.hy926 cells was likely associated with the regulation of isoquercitrin on Akt/GSK3β signaling pathway and that isoquercitrin could be used clinically to interfere with the progression of endothelial injury-associated cardiovascular disease. Full article

(This article belongs to the Section Medicinal Chemistry)

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10 pages, 3375 KiB

Open AccessArticle

Molecular Cloning of cpcU and Heterodimeric Bilin Lyase Activity Analysis of CpcU and CpcS for Attachment of Phycocyanobilin to Cys-82 on the β-Subunit of Phycocyanin in Arthrospira platensis FACHB314

by Fei Wu, Xiaonan Zang, Xuecheng Zhang, Ran Zhang, Xiaoyun Huang, Lulu Hou, Minjie Jiang, Chang Liu and Chunhong Pang

Molecules 2016, 21(3), 357; https://doi.org/10.3390/molecules21030357 - 16 Mar 2016

Cited by 11 | Viewed by 5039

Abstract

A new bilin lyase gene cpcU was cloned from Arthrospira platensis FACHB314 to study the assembly of the phycocyanin β-Subunit. Two recombinant plasmids, one contained the phycocyanobilin (PCB) producing genes (hoxI and pcyA), while the other contained the gene of the [...] Read more.

A new bilin lyase gene cpcU was cloned from Arthrospira platensis FACHB314 to study the assembly of the phycocyanin β-Subunit. Two recombinant plasmids, one contained the phycocyanobilin (PCB) producing genes (hoxI and pcyA), while the other contained the gene of the β-Subunit of phycobiliprotein (cpcB) and the lyase gene (cpcU, cpcS, or cpcU/S) were constructed and separately transferred into Escherichia coli in order to test the activities of relevant lyases for catalyzing PCB addition to CpcB during synthesizing fluorescent β-PC of A. platensis FACHB314. The fluorescence intensity examination showed that Cys-82 maybe the active site for the β-Subunit binding to PCBs and the attachment could be carried out by CpcU, CpcS, or co-expressed cpcU/S in A. platensis FACHB314. Full article

(This article belongs to the Section Molecular Diversity)

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6 pages, 14163 KiB

Open AccessArticle

Synthesis of Fluorinated Polymers and Evaluation of Wettability

by Tamami Kimura, Maria Carmelita Kasuya, Kenichi Hatanaka and Koji Matsuoka

Molecules 2016, 21(3), 358; https://doi.org/10.3390/molecules21030358 - 17 Mar 2016

Cited by 6 | Viewed by 4928

Abstract

Two kinds of fluorinated polymers were synthesized: an acrylate polymer having a fluorinated triethylene glycol as a pendant group (2a) and a fluoroalkyl acrylate polymer (2b). The contact angle of these fluorinated polymers against water, non-fluorinated alcohols and fluorinated alcohols were evaluated. As [...] Read more.

Two kinds of fluorinated polymers were synthesized: an acrylate polymer having a fluorinated triethylene glycol as a pendant group (2a) and a fluoroalkyl acrylate polymer (2b). The contact angle of these fluorinated polymers against water, non-fluorinated alcohols and fluorinated alcohols were evaluated. As compared with the fluoroalkyl polymer (2b), fluoroethylene glycol polymer (2a) showed smaller contact angle against water and non-fluorinated alcohols. This supports the proposition that changing the alkyl chain into the ethylene glycol-type chain gave some interaction between etheric oxygen and water or non-fluorinated alcohols. In addition, fluoroalkyl acrylate polymer (2b) showed remarkably low values of critical surface tension. Full article

(This article belongs to the Section Molecular Diversity)

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45 pages, 2240 KiB

Open AccessReview

New Potential Pharmacological Functions of Chinese Herbal Medicines via Regulation of Autophagy

by Betty Yuen Kwan Law, Simon Wing Fai Mok, An Guo Wu, Christopher Wai Kei Lam, Margaret Xin Yi Yu and Vincent Kam Wai Wong

Molecules 2016, 21(3), 359; https://doi.org/10.3390/molecules21030359 - 17 Mar 2016

Cited by 59 | Viewed by 14199

Abstract

Autophagy is a universal catabolic cellular process for quality control of cytoplasm and maintenance of cellular homeostasis upon nutrient deprivation and environmental stimulus. It involves the lysosomal degradation of cellular components such as misfolded proteins or damaged organelles. Defects in autophagy are implicated [...] Read more.

Autophagy is a universal catabolic cellular process for quality control of cytoplasm and maintenance of cellular homeostasis upon nutrient deprivation and environmental stimulus. It involves the lysosomal degradation of cellular components such as misfolded proteins or damaged organelles. Defects in autophagy are implicated in the pathogenesis of diseases including cancers, myopathy, neurodegenerations, infections and cardiovascular diseases. In the recent decade, traditional drugs with new clinical applications are not only commonly found in Western medicines, but also highlighted in Chinese herbal medicines (CHM). For instance, pharmacological studies have revealed that active components or fractions from Chaihu (Radix bupleuri), Hu Zhang (Rhizoma polygoni cuspidati), Donglingcao (Rabdosia rubesens), Hou po (Cortex magnoliae officinalis) and Chuan xiong (Rhizoma chuanxiong) modulate cancers, neurodegeneration and cardiovascular disease via autophagy. These findings shed light on the potential new applications and formulation of CHM decoctions via regulation of autophagy. This article reviews the roles of autophagy in the pharmacological actions of CHM and discusses their new potential clinical applications in various human diseases. Full article

(This article belongs to the Collection Herbal Medicine Research)

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13 pages, 4902 KiB

Open AccessArticle

Flavonoids, Antioxidant Potential, and Acetylcholinesterase Inhibition Activity of the Extracts from the Gametophyte and Archegoniophore of Marchantia polymorpha L.

by Xin Wang, Jianguo Cao, Yuhuan Wu, Quanxi Wang and Jianbo Xiao

Molecules 2016, 21(3), 360; https://doi.org/10.3390/molecules21030360 - 17 Mar 2016

Cited by 40 | Viewed by 8550

Abstract

Marchantia polymorpha L. is a representative bryophyte used as a traditional Chinese medicinal herb for scald and pneumonia. The phytochemicals in M. polymorpha L. are terpenoids and flavonoids, among which especially the flavonoids show significant human health benefits. Many researches on the gametophyte [...] Read more.

Marchantia polymorpha L. is a representative bryophyte used as a traditional Chinese medicinal herb for scald and pneumonia. The phytochemicals in M. polymorpha L. are terpenoids and flavonoids, among which especially the flavonoids show significant human health benefits. Many researches on the gametophyte of M. polymorpha L. have been reported. However, as the reproductive organ of M. polymorpha L., the bioactivity and flavonoids profile of the archegoniophore have not been reported, so in this work the flavonoid profiles, antioxidant and acetylcholinesterase inhibition activities of the extracts from the archegoniophore and gametophyte of M. polymorpha L. were compared by radical scavenging assay methods (DPPH, ABTS, O²⁻), reducing power assay, acetylcholinesterase inhibition assay and LC-MS analysis. The results showed that the total flavonoids content in the archegoniophore was about 10-time higher than that of the gametophyte. Differences between the archegoniophore and gametophyte of M. polymorpha L. were observed by LC-MS analysis. The archegoniophore extracts showed stronger bio-activities than those of the gametophyte. The archegoniophore extract showed a significant acetylcholinesterase inhibition, while the gametophyte extract hardly inhibited it. Full article

(This article belongs to the Section Natural Products Chemistry)

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10 pages, 943 KiB

Open AccessArticle

Fumigant Toxicity of Lamiaceae Plant Essential Oils and Blends of Their Constituents against Adult Rice Weevil Sitophilus oryzae

by Sung-Woong Kim, Hyo-Rim Lee, Myeong-Jin Jang, Chan-Sik Jung and Il-Kwon Park

Molecules 2016, 21(3), 361; https://doi.org/10.3390/molecules21030361 - 16 Mar 2016

Cited by 47 | Viewed by 7063

Abstract

To find a new and safe alternative to conventional insecticides, we evaluated the fumigant toxicity of eight Lamiaceae essential oils and their constituents against the adult rice weevil Sitophilus oryzae. Of the eight species tested, hyssop (Hyssopus offcinalis), majoram ( [...] Read more.

To find a new and safe alternative to conventional insecticides, we evaluated the fumigant toxicity of eight Lamiaceae essential oils and their constituents against the adult rice weevil Sitophilus oryzae. Of the eight species tested, hyssop (Hyssopus offcinalis), majoram (Origanum majorana), and Thymus zygis essential oils showed strong fumigant toxicity against S. oryzae adults at 25 mg/L air concentration. Constituents of active essential oils were analyzed by gas chromatography coupled to flame ionization detector (FID) and gas chromatography-mass spectrometry. A total of 13, 15, and 17 compounds were identified from hyssop, majoram, and Thymus zygis essential oils, respectively. Pinocamphone and isopinocamphone were isolated by open column chromatography. Among the test compounds, pinocamphone and isopinocamphone showed the strongest fumigant toxicity against S. oryzae. Sabinene hydrate, linalool, α-terpineol, and terpinen-4-ol exhibited 100% fumigant toxicity against S. oryzae at 3.9 mg/L air concentration. The measured toxicity of the artificial blends of the constituents identified in hyssop, majoram, and Thymus zygis oils indicated that isopinocamphone, terpine-4-ol, and linalool were major contributors to the fumigant toxicity of the artificial blend, respectively. Full article

(This article belongs to the Collection Recent Advances in Flavors and Fragrances)

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15 pages, 1519 KiB

Open AccessArticle

Searching for Multi-Targeting Neurotherapeutics against Alzheimer’s: Discovery of Potent AChE-MAO B Inhibitors through the Decoration of the 2H-Chromen-2-one Structural Motif

by Leonardo Pisani, Roberta Farina, Ramon Soto-Otero, Nunzio Denora, Giuseppe Felice Mangiatordi, Orazio Nicolotti, Estefania Mendez-Alvarez, Cosimo Damiano Altomare, Marco Catto and Angelo Carotti

Molecules 2016, 21(3), 362; https://doi.org/10.3390/molecules21030362 - 17 Mar 2016

Cited by 50 | Viewed by 7750

Abstract

The need for developing real disease-modifying drugs against neurodegenerative syndromes, particularly Alzheimer’s disease (AD), shifted research towards reliable drug discovery strategies to unveil clinical candidates with higher therapeutic efficacy than single-targeting drugs. By following the multi-target approach, we designed and synthesized a novel [...] Read more.

The need for developing real disease-modifying drugs against neurodegenerative syndromes, particularly Alzheimer’s disease (AD), shifted research towards reliable drug discovery strategies to unveil clinical candidates with higher therapeutic efficacy than single-targeting drugs. By following the multi-target approach, we designed and synthesized a novel class of dual acetylcholinesterase (AChE)-monoamine oxidase B (MAO-B) inhibitors through the decoration of the 2H-chromen-2-one skeleton. Compounds bearing a propargylamine moiety at position 3 displayed the highest in vitro inhibitory activities against MAO-B. Within this series, derivative 3h emerged as the most interesting hit compound, being a moderate AChE inhibitor (IC₅₀ = 8.99 µM) and a potent and selective MAO-B inhibitor (IC₅₀ = 2.8 nM). Preliminary studies in human neuroblastoma SH-SY5Y cell lines demonstrated its low cytotoxicity and disclosed a promising neuroprotective effect at low doses (0.1 µM) under oxidative stress conditions promoted by two mitochondrial toxins (oligomycin-A and rotenone). In a Madin-Darby canine kidney (MDCK)II-MDR1 cell-based transport study, Compound 3h was able to permeate the BBB-mimicking monolayer and did not result in a glycoprotein-p (P-gp) substrate, showing an efflux ratio = 0.96, close to that of diazepam. Full article

(This article belongs to the Special Issue Molecules against Alzheimer)

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26 pages, 250 KiB

Open AccessArticle

Comparison of the Profile and Composition of Volatiles in Coniferous Needles According to Extraction Methods

by Yonjin Jun, Sang Mi Lee, Hyun Kyoung Ju, Hong Jin Lee, Hyung-Kyoon Choi, Gyeong Suk Jo and Young-Suk Kim

Molecules 2016, 21(3), 363; https://doi.org/10.3390/molecules21030363 - 17 Mar 2016

Cited by 11 | Viewed by 5945

Abstract

The enantiomeric distribution and profile of volatiles in plants, which affect the biological and organoleptic properties, can be varied depending on extraction methods as well as their cultivars. The secondary volatile components of the needles of three conifer cultivars (Chamaecyparispisifera, Chamaecyparisobtusa [...] Read more.

The enantiomeric distribution and profile of volatiles in plants, which affect the biological and organoleptic properties, can be varied depending on extraction methods as well as their cultivars. The secondary volatile components of the needles of three conifer cultivars (Chamaecyparispisifera, Chamaecyparisobtusa, and Thujaorientalis) were compared. Furthermore, the effects of three different extraction methods—solid-phase microextraction (SPME), steam distillation (SD), and solvent extraction (SE)—on the composition and enantiomeric distribution of those volatiles were elucidated. Monoterpene hydrocarbons predominated in all samples, and the compositions of sesquiterpenes and diterpenes differed according to the cultivar. In particular, the yields of oxygenated monoterpenes and sesquiterpenes were greatest for SD, whereas those of sesquiterpenes and diterpenes were highest for SE. On the other hand, more monoterpenes with higher volatility could be obtained with SPME and SD than when using SE. In addition, the enantiomeric composition of nine chiral compounds found in three cultivars differed according to their chemotype. There were also some differences in the yielded oxygenated monoterpenes and sesquiterpene hydrocarbons, but not monoterpene hydrocarbons, according to the extraction method. These results demonstrate that the extraction methods used as well as the cultivars influence the measured volatile profiles and enantiomeric distribution of coniferous needle extracts. Full article

(This article belongs to the Collection Recent Advances in Flavors and Fragrances)

17 pages, 4142 KiB

Open AccessArticle

Silver Nanoparticles Exhibit the Dose-Dependent Anti-Proliferative Effect against Human Squamous Carcinoma Cells Attenuated in the Presence of Berberine

by Arkadiusz Dziedzic, Robert Kubina, Rafał J. Bułdak, Magda Skonieczna and Krzysztof Cholewa

Molecules 2016, 21(3), 365; https://doi.org/10.3390/molecules21030365 - 17 Mar 2016

Cited by 65 | Viewed by 10309

Abstract

The biological activity of nanosize silver particles towards oral epithelium-derived carcinoma seems to be still underinvestigated. We evaluated the influence of low doses of nanosize scale silver particles on the proliferation and viability of malignant oral epithelial keratinocytes in vitro, alone and [...] Read more.

The biological activity of nanosize silver particles towards oral epithelium-derived carcinoma seems to be still underinvestigated. We evaluated the influence of low doses of nanosize scale silver particles on the proliferation and viability of malignant oral epithelial keratinocytes in vitro, alone and in conjunction with the plant alkaloid berberine. Cells of human tongue squamous carcinoma SCC-25 (ATCC CRL-1628), cultivated with the mixture of Dulbecco's modified Eagle’s medium, were exposed to silver nanoparticles alone (AgNPs, concentrations from 0.31 to 10 μg/mL) and to a combination of AgNPs with berberine chloride (BER, 1/2 IC₅₀ concentration) during 24 h and 48 h. The cytotoxic activity of AgNPs with diameters of 10 nm ± 4 nm was measured by 3-(4,5-dimethyl-2-thiazyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. Cell cycle analysis was performed by treating cells with propidium iodide followed by flow-activated cell sorting. RT-QPCR reaction was used to assess expression of anti-apoptotic proteins Bcl-2 and pro-apoptotic protein Bcl-2-associated X protein Bax genes expression. Monodisperse silver nanoparticles at a concentration of 10 μg/mL arrested SCC-25 cells cycle after 48 h at the G0/G1 phase in a dose- and time-dependent manner through disruption G0/G1 checkpoint, with increase of Bax/Bcl-2 ratio gene expression. AgNPs exhibit cytotoxic effects on SCC-25 malignant oral epithelial keratinocytes, which is diminished when combined with BER. The AgNPs concentration required to inhibit the growth of carcinoma cells by 50% (IC₅₀) after 48 h was estimated at 5.19 μg/mL. AgNPs combined with BER increased the expression of Bcl-2 while decreasing the ratio of Bax/Bcl-2 in SCC-25 cells. Silver particles at low doses therefore reduce the proliferation and viability of oral squamous cell carcinoma cells. SCC-25 cells are susceptible to damage from AgNPs-induced stress, which can be regulated by the natural alkaloid berberine, suggesting that nanoparticles may be potentially used in a chemoprevention/chemotherapy by augmentation of action of standard anti-cancer drugs. Full article

(This article belongs to the Section Metabolites)

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11 pages, 1108 KiB

Open AccessArticle

Fluoride-Promoted Esterification (FPE) Chemistry: A Robust Route to Bis-MPA Dendrons and Their Postfunctionalization

by Patrik Stenström, Oliver C. J. Andrén and Michael Malkoch

Molecules 2016, 21(3), 366; https://doi.org/10.3390/molecules21030366 - 17 Mar 2016

Cited by 18 | Viewed by 6885

Abstract

Bifunctional dendrons based on 2,2-bis(methylol)propionic acid (bis-MPA) are highly desirable scaffolds for biomedical applications. This is due to their flawless nature and large and exact number of functional groups as well as being biodegradable and biocompatible. Herein, we describe a facile divergent growth [...] Read more.

Bifunctional dendrons based on 2,2-bis(methylol)propionic acid (bis-MPA) are highly desirable scaffolds for biomedical applications. This is due to their flawless nature and large and exact number of functional groups as well as being biodegradable and biocompatible. Herein, we describe a facile divergent growth approach to their synthesis from monobenzylated tetraethylene glycol and post functionalization utilizing fluoride-promoted esterification (FPE) chemistry protocols. The scaffolds, presenting selectively deprotectable hydroxyls in the periphery and at the focal point, were isolated on a multigram scale with excellent purity up to the fourth generation dendron with a molecular weight of 2346 Da in seven reactions with a total yield of 50%. The third generation dendron was used as a model compound to demonstrate its functionalizability. Selective deprotection of the dendron’s focal point was achieved with an outstanding yield of 94%, and biotin as well as azido functionalities were introduced to its focal point and periphery, respectively, through FPE chemistry. Bulky disperse red dyes were clicked through CuAAC to the dendron’s azido groups, giving a biotinylated dendron with multivalent dyes with a molecular weight of 6252 Da in a total yield of 37% in five reactions with an average yield of 82% starting from the third generation focally and peripherally protected dendron. FPE chemistry proved to be a superb improvement over previous protocols towards bis-MPA dendrons as high purity and yields were obtained with less toxic solvents and greatly improved monomer utilization. Full article

(This article belongs to the Special Issue Functional Dendrimers)

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11 pages, 458 KiB

Open AccessArticle

Pharmacokinetics of Maleic Acid as a Food Adulterant Determined by Microdialysis in Rat Blood and Kidney Cortex

by Mei-Ling Hou, Chia-Ming Lu, Chi-Hung Lin, Lie-Chwen Lin and Tung-Hu Tsai

Molecules 2016, 21(3), 367; https://doi.org/10.3390/molecules21030367 - 17 Mar 2016

Cited by 9 | Viewed by 6154

Abstract

Maleic acid has been shown to be used as a food adulterant in the production of modified starch by the Taiwan Food and Drug Administration. Due to the potential toxicity of maleic acid to the kidneys, this study aimed to develop an analytical [...] Read more.

Maleic acid has been shown to be used as a food adulterant in the production of modified starch by the Taiwan Food and Drug Administration. Due to the potential toxicity of maleic acid to the kidneys, this study aimed to develop an analytical method to investigate the pharmacokinetics of maleic acid in rat blood and kidney cortex. Multiple microdialysis probes were simultaneously inserted into the jugular vein and the kidney cortex for sampling after maleic acid administration (10 or 30 mg/kg, i.v., respectively). The pharmacokinetic results demonstrated that maleic acid produced a linear pharmacokinetic phenomenon within the doses of 10 and 30 mg/kg. The area under concentration versus time curve (AUC) of the maleic acid in kidney cortex was 5-fold higher than that in the blood after maleic acid administration (10 and 30 mg/kg, i.v., respectively), indicating that greater accumulation of maleic acid occurred in the rat kidney. Full article

(This article belongs to the Collection Phytochemicals: Biosynthesis, Metabolism and Biological Activities)

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14 pages, 6182 KiB

Open AccessArticle

Binding Mode and Selectivity of Steroids towards Glucose-6-phosphate Dehydrogenase from the Pathogen Trypanosoma cruzi

by Cecilia Ortiz, Francesca Moraca, Andrea Medeiros, Maurizio Botta, Niall Hamilton and Marcelo A. Comini

Molecules 2016, 21(3), 368; https://doi.org/10.3390/molecules21030368 - 17 Mar 2016

Cited by 20 | Viewed by 7282

Abstract

Glucose-6-phosphate dehydrogenase (G6PDH) plays a housekeeping role in cell metabolism by generating reducing power (NADPH) and fueling the production of nucleotide precursors (ribose-5-phosphate). Based on its indispensability for pathogenic parasites from the genus Trypanosoma, G6PDH is considered a drug target candidate. Several [...] Read more.

Glucose-6-phosphate dehydrogenase (G6PDH) plays a housekeeping role in cell metabolism by generating reducing power (NADPH) and fueling the production of nucleotide precursors (ribose-5-phosphate). Based on its indispensability for pathogenic parasites from the genus Trypanosoma, G6PDH is considered a drug target candidate. Several steroid-like scaffolds were previously reported to target the activity of G6PDH. Epiandrosterone (EA) is an uncompetitive inhibitor of trypanosomal G6PDH for which its binding site to the enzyme remains unknown. Molecular simulation studies with the structure of Trypanosoma cruzi G6PDH revealed that EA binds in a pocket close to the G6P binding-site and protrudes into the active site blocking the interaction between substrates and hence catalysis. Site directed mutagenesis revealed the important steroid-stabilizing effect of residues (L80, K83 and K84) located on helix α-1 of T. cruzi G6PDH. The higher affinity and potency of 16α-Br EA by T. cruzi G6PDH is explained by the formation of a halogen bond with the hydrogen from the terminal amide of the NADP+-nicotinamide. At variance with the human enzyme, the inclusion of a 21-hydroxypregnane-20-one moiety to a 3β-substituted steroid is detrimental for T. cruzi G6PDH inhibition. The species-specificity of certain steroid derivatives towards the parasite G6PDH and the corresponding biochemically validated binding models disclosed in this work may prove valuable for the development of selective inhibitors against the pathogen’s enzyme. Full article

(This article belongs to the Special Issue COST CM1307: Targeted Chemotherapy towards Diseases Caused by Endoparasites—Proceedings in Medicinal and Natural Product Chemistry)

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16 pages, 1991 KiB

Open AccessArticle

Production of Fusaric Acid by Fusarium spp. in Pure Culture and in Solid Medium Co-Cultures

by Nadine Bohni, Valérie Hofstetter, Katia Gindro, Bart Buyck, Olivier Schumpp, Samuel Bertrand, Michel Monod and Jean-Luc Wolfender

Molecules 2016, 21(3), 370; https://doi.org/10.3390/molecules21030370 - 18 Mar 2016

Cited by 28 | Viewed by 10557

Abstract

The ability of fungi isolated from nails of patients suffering from onychomycosis to induce de novo production of bioactive compounds in co-culture was examined. Comparison between the metabolite profiles produced by Sarocladium strictum, by Fusarium oxysporum, and by these two species [...] Read more.

The ability of fungi isolated from nails of patients suffering from onychomycosis to induce de novo production of bioactive compounds in co-culture was examined. Comparison between the metabolite profiles produced by Sarocladium strictum, by Fusarium oxysporum, and by these two species in co-culture revealed de novo induction of fusaric acid based on HRMS. Structure confirmation of this toxin, using sensitive microflow NMR, required only three 9-cm Petri dishes of fungal culture. A targeted metabolomics study based on UHPLC-HRMS confirmed that the production of fusaric acid was strain-dependent. Furthermore, the detected toxin levels suggested that onychomycosis-associated fungal strains of the F. oxysporum and F. fujikuroi species complexes are much more frequently producing fusaric acid, and in higher amount, than strains of the F. solani species complex. Fusarium strains producing no significant amounts of this compound in pure culture, were shown to de novo produce that compound when grown in co-culture. The role of fusaric acid in fungal virulence and defense is discussed. Full article

(This article belongs to the Special Issue Applications of Metabolomics within Natural Products Chemistry)

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26 pages, 2365 KiB

Open AccessReview

Coenzyme Q and Its Role in the Dietary Therapy against Aging

by Alfonso Varela-López, Francesca Giampieri, Maurizio Battino and José L. Quiles

Molecules 2016, 21(3), 373; https://doi.org/10.3390/molecules21030373 - 18 Mar 2016

Cited by 74 | Viewed by 13176

Abstract

Coenzyme Q (CoQ) is a naturally occurring molecule located in the hydrophobic domain of the phospholipid bilayer of all biological membranes. Shortly after being discovered, it was recognized as an essential electron transport chain component in mitochondria where it is particularly abundant. Since [...] Read more.

Coenzyme Q (CoQ) is a naturally occurring molecule located in the hydrophobic domain of the phospholipid bilayer of all biological membranes. Shortly after being discovered, it was recognized as an essential electron transport chain component in mitochondria where it is particularly abundant. Since then, more additional roles in cell physiology have been reported, including antioxidant, signaling, death prevention, and others. It is known that all cells are able to synthesize functionally sufficient amounts of CoQ under normal physiological conditions. However, CoQ is a molecule found in different dietary sources, which can be taken up and incorporated into biological membranes. It is known that mitochondria have a close relationship with the aging process. Additionally, delaying the aging process through diet has aroused the interest of scientists for many years. These observations have stimulated investigation of the anti-aging potential of CoQ and its possible use in dietary therapies to alleviate the effects of aging. In this context, the present review focus on the current knowledge and evidence the roles of CoQ cells, its relationship with aging, and possible implications of dietary CoQ in relation to aging, lifespan or age-related diseases. Full article

(This article belongs to the Special Issue 20th Anniversary of Molecules—Recent Advances in Natural Products)

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15 pages, 2964 KiB

Open AccessArticle

Compound Library Screening Identified Cardiac Glycoside Digitoxin as an Effective Growth Inhibitor of Gefitinib-Resistant Non-Small Cell Lung Cancer via Downregulation of α-Tubulin and Inhibition of Microtubule Formation

by Yi-Ze Zhang, Xi Chen, Xing-Xing Fan, Jian-Xing He, Jun Huang, Da-Kai Xiao, Yan-Ling Zhou, Sen-You Zheng, Jia-Hui Xu, Xiao-Jun Yao, Liang Liu and Elaine Lai-Han Leung

Molecules 2016, 21(3), 374; https://doi.org/10.3390/molecules21030374 - 18 Mar 2016

Cited by 28 | Viewed by 8439

Abstract

Non-small-cell lung cancer (NSCLC) dominates over 85% of all lung cancer cases. Epidermal growth factor receptor (EGFR) activating mutation is a common situation in NSCLC. In the clinic, molecular-targeting with Gefitinib as a tyrosine kinase inhibitor (TKI) for EGFR downstream signaling is initially [...] Read more.

Non-small-cell lung cancer (NSCLC) dominates over 85% of all lung cancer cases. Epidermal growth factor receptor (EGFR) activating mutation is a common situation in NSCLC. In the clinic, molecular-targeting with Gefitinib as a tyrosine kinase inhibitor (TKI) for EGFR downstream signaling is initially effective. However, drug resistance frequently happens due to additional mutation on EGFR, such as substitution from threonine to methionine at amino acid position 790 (T790M). In this study, we screened a traditional Chinese medicine (TCM) compound library consisting of 800 single compounds in TKI-resistance NSCLC H1975 cells, which contains substitutions from leucine to arginine at amino acid 858 (L858R) and T790M mutation on EGFR. Attractively, among these compounds there are 24 compounds CC₅₀ of which was less than 2.5 μM were identified. We have further investigated the mechanism of the most effective one, Digitoxin. It showed a significantly cytotoxic effect in H1975 cells by causing G2 phase arrest, also remarkably activated 5′ adenosine monophosphate-activated protein kinase (AMPK). Moreover, we first proved that Digitoxin suppressed microtubule formation through decreasing α-tubulin. Therefore, it confirmed that Digitoxin effectively depressed the growth of TKI-resistance NSCLC H1975 cells by inhibiting microtubule polymerization and inducing cell cycle arrest. Full article

(This article belongs to the Collection Herbal Medicine Research)

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20 pages, 4865 KiB

Open AccessArticle

A Novel Biomolecule-Mediated Reduction of Graphene Oxide: A Multifunctional Anti-Cancer Agent

by Yun-Jung Choi, Eunsu Kim, JaeWoong Han, Jin-Hoi Kim and Sangiliyandi Gurunathan

Molecules 2016, 21(3), 375; https://doi.org/10.3390/molecules21030375 - 18 Mar 2016

Cited by 64 | Viewed by 9552

Abstract

Graphene oxide (GO) is a monolayer of carbon atoms that form a dense honeycomb structure, consisting of hydroxyl and epoxide functional groups on the two accessible sides and carboxylic groups at the edges. In contrast, graphene is a two-dimensional sheet of sp2-hybridized carbon [...] Read more.

Graphene oxide (GO) is a monolayer of carbon atoms that form a dense honeycomb structure, consisting of hydroxyl and epoxide functional groups on the two accessible sides and carboxylic groups at the edges. In contrast, graphene is a two-dimensional sheet of sp2-hybridized carbon atoms packed into a honeycomb lattice. Graphene has great potential for use in biomedical applications due to its excellent physical and chemical properties. In this study, we report a facile and environmentally friendly approach for the synthesis of reduced graphene oxide (rGO) using uric acid (UA). The synthesized uric acid-reduced graphene oxide (UA-rGO) was fully characterized by ultraviolet-visible (UV-Vis) absorption spectra, X-ray diffraction (XRD), dynamic light scattering (DLS), Fourier transform infrared (FTIR), scanning electron microscopy (SEM), and Raman spectroscopy. GO and UA-rGO induced a dose-dependent decrease in cell viability and induced cytotoxicity in human ovarian cancer cells. The results from this study suggest that UA-rGO could cause apoptosis in mammalian cells. The toxicity of UA-rGO is significantly higher than GO. Based on our findings, UA-rGO shows cytotoxic effects against human ovarian cancer cells, and its synthesis is environmentally friendly. UA-rGO significantly inhibits cell viability by increasing lactate dehydrogenase (LDH) release, reactive oxygen species (ROS) generation, activation of caspase-3, and DNA fragmentation. This is the first report to describe the comprehensive effects of UA-rGO in ovarian cancer cells. We believe that the functional aspects of newly synthesized UA-rGO will provide advances towards various biomedical applications in the near future. Full article

(This article belongs to the Section Natural Products Chemistry)

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18 pages, 7693 KiB

Open AccessArticle

Fluidized Bed Membrane Reactors for Ultra Pure H₂ Production—A Step forward towards Commercialization

by Arash Helmi, Ekain Fernandez, Jon Melendez, David Alfredo Pacheco Tanaka, Fausto Gallucci and Martin Van Sint Annaland

Molecules 2016, 21(3), 376; https://doi.org/10.3390/molecules21030376 - 19 Mar 2016

Cited by 53 | Viewed by 8637

Abstract

In this research the performance of a fluidized bed membrane reactor for high temperature water gas shift and its long term stability was investigated to provide a proof-of-concept of the new system at lab scale. A demonstration unit with a capacity of 1 [...] Read more.

In this research the performance of a fluidized bed membrane reactor for high temperature water gas shift and its long term stability was investigated to provide a proof-of-concept of the new system at lab scale. A demonstration unit with a capacity of 1 Nm³/h of ultra-pure H₂ was designed, built and operated over 900 h of continuous work. Firstly, the performance of the membranes were investigated at different inlet gas compositions and at different temperatures and H₂ partial pressure differences. The membranes showed very high H₂ fluxes (3.89 × 10⁻⁶ mol·m⁻²·Pa⁻¹·s⁻¹ at 400 °C and 1 atm pressure difference) with a H₂/N₂ ideal perm-selectivity (up to 21,000 when integrating five membranes in the module) beyond the DOE 2015 targets. Monitoring the performance of the membranes and the reactor confirmed a very stable performance of the unit for continuous high temperature water gas shift under bubbling fluidization conditions. Several experiments were carried out at different temperatures, pressures and various inlet compositions to determine the optimum operating window for the reactor. The obtained results showed high hydrogen recovery factors, and very low CO concentrations at the permeate side (in average <10 ppm), so that the produced hydrogen can be directly fed to a low temperature PEM fuel cell. Full article

(This article belongs to the Special Issue Membrane Catalysis)

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11 pages, 478 KiB

Open AccessArticle

Screening of Satureja subspicata Vis. Honey by HPLC-DAD, GC-FID/MS and UV/VIS: Prephenate Derivatives as Biomarkers

by Igor Jerković, Marina Kranjac, Zvonimir Marijanović, Marina Zekić, Ani Radonić and Carlo Ignazio Giovanni Tuberoso

Molecules 2016, 21(3), 377; https://doi.org/10.3390/molecules21030377 - 21 Mar 2016

Cited by 11 | Viewed by 6407

Abstract

The samples of Satureja subspicata Vis. honey were confirmed to be unifloral by melissopalynological analysis with the characteristic pollen share from 36% to 71%. Bioprospecting of the samples was performed by HPLC-DAD, GC-FID/MS, and UV/VIS. Prephenate derivatives were shown to be dominant by [...] Read more.

The samples of Satureja subspicata Vis. honey were confirmed to be unifloral by melissopalynological analysis with the characteristic pollen share from 36% to 71%. Bioprospecting of the samples was performed by HPLC-DAD, GC-FID/MS, and UV/VIS. Prephenate derivatives were shown to be dominant by the HPLC-DAD analysis, particularly phenylalanine (167.8 mg/kg) and methyl syringate (MSYR, 114.1 mg/kg), followed by tyrosine and benzoic acid. Higher amounts of MSYR (3–4 times) can be pointed out for distinguishing S. subspicata Vis. honey from other Satureja spp. honey types. GC-FID/MS analysis of ultrasonic solvent extracts of the samples revealed MSYR (46.68%, solvent pentane/Et₂O 1:2 (v/v); 52.98%, solvent CH₂Cl₂) and minor abundance of other volatile prephenate derivatives, as well as higher aliphatic compounds characteristic of the comb environment. Two combined extracts (according to the solvents) of all samples were evaluated for their antioxidant properties by FRAP and DPPH assay; the combined extracts demonstrated higher activity (at lower concentrations) in comparison with the average honey sample. UV/VIS analysis of the samples was applied for determination of CIE Lab colour coordinates, total phenolics (425.38 mg GAE/kg), and antioxidant properties (4.26 mmol Fe²⁺/kg (FRAP assay) and 0.8 mmol TEAC/kg (DDPH assay)). Full article

(This article belongs to the Collection Recent Advances in Flavors and Fragrances)

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11 pages, 8214 KiB

Open AccessArticle

Functionalization of Calcium Sulfate/Bioglass Scaffolds with Zinc Oxide Whisker

by Cijun Shuai, Jianhua Zhou, Dan Gao, Chengde Gao, Pei Feng and Shuping Peng

Molecules 2016, 21(3), 378; https://doi.org/10.3390/molecules21030378 - 18 Mar 2016

Cited by 22 | Viewed by 5967

Abstract

There are urgent demands for satisfactory antibacterial activity and mechanical properties of bone scaffolds. In this study, zinc oxide whisker (ZnOw) was introduced into calcium sulfate/bioglass scaffolds. Antimicrobial behavior was analyzed using Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). [...] Read more.

There are urgent demands for satisfactory antibacterial activity and mechanical properties of bone scaffolds. In this study, zinc oxide whisker (ZnOw) was introduced into calcium sulfate/bioglass scaffolds. Antimicrobial behavior was analyzed using Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). The results showed that the scaffolds presented a strong antibacterial activity after introducing ZnOw, due to the antibacterial factors released from the degradation of ZnO. Moreover, ZnOw was also found to have a distinct reinforcing effect on mechanical properties. This was ascribed to whisker pull-out, crack bridging, crack deflection, crack branching and other toughening mechanisms. In addition, the cell culture experiments showed that the scaffolds with ZnOw had a good biocompatibility. Full article

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12 pages, 1468 KiB

Open AccessFeature PaperArticle

Clean Transformation of Ethanol to Useful Chemicals. The Behavior of a Gold-Modified Silicalite Catalyst

by Ermelinda Falletta, Michele Rossi, Joaquim Henrique Teles and Cristina Della Pina

Molecules 2016, 21(3), 379; https://doi.org/10.3390/molecules21030379 - 19 Mar 2016

Cited by 4 | Viewed by 7381

Abstract

Upon addition of gold to silicalite-1 pellets (a MFI-type zeolite), the vapor phase oxidation of ethanol could be addressed to acetaldehyde or acetic acid formation. By optimizing the catalyst composition and reaction conditions, the conversion of ethanol could be tuned to acetaldehyde with [...] Read more.

Upon addition of gold to silicalite-1 pellets (a MFI-type zeolite), the vapor phase oxidation of ethanol could be addressed to acetaldehyde or acetic acid formation. By optimizing the catalyst composition and reaction conditions, the conversion of ethanol could be tuned to acetaldehyde with 97% selectivity at 71% conversion or to acetic acid with 78% selectivity at total conversion. Considering that unloaded silicalite-1 was found to catalyze the dehydration of ethanol to diethylether or ethene, a green approach for the integrated production of four important chemicals is herein presented. This is based on renewable ethanol as a reagent and a modular catalytic process. Full article

(This article belongs to the Special Issue Coinage Metal (Copper, Silver, and Gold) Catalysis)

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13 pages, 1260 KiB

Open AccessArticle

Development of Wax-Incorporated Emulsion Gel Beads for the Encapsulation and Intragastric Floating Delivery of the Active Antioxidant from Tamarindus indica L.

by Sitthiphong Soradech, Intira Petchtubtim, Jeerayu Thongdon-A and Thanchanok Muangman

Molecules 2016, 21(3), 380; https://doi.org/10.3390/molecules21030380 - 22 Mar 2016

Cited by 11 | Viewed by 7867

Abstract

In this study, tamarind (Tamarindus indica L.) seed extracts with potential antioxidant activity and toxicity to cancer cells were developed as functional foods and nutraceutical ingredients in the form of emulsion gel beads. Three extracts were obtained from ethanol and water: TSCH50, [...] Read more.

In this study, tamarind (Tamarindus indica L.) seed extracts with potential antioxidant activity and toxicity to cancer cells were developed as functional foods and nutraceutical ingredients in the form of emulsion gel beads. Three extracts were obtained from ethanol and water: TSCH50, TSCH95 and TSCH. All extracts exhibited high potential for superoxide anion scavenging activity over the IC₅₀ range < 5–11 µg/mL and had no toxic effects on normal cells, however, the water extract (TSCH) was the most effective due to its free radical scavenging activity and toxicity in mitochondrial membranes of cancer cells. Next a study was designed to develop a new formulation for encapsulation and intragastric floating delivery of tamarind seed extract (TSCH) using wax-incorporated emulsion gel beads, which were prepared using a modified ionotropic gelation technique. Tamarind seed extract at 1% (w/w) was used as the active ingredient in all formulations. The effect of the types and amounts of wax on the encapsulation efficiency and percentage of the active release of alginate gel beads was also investigated. The results demonstrated that the incorporation of both waxes into the gel beads had an effect on the percentage of encapsulation efficiency (%) and the percentage of the active ingredient release. Furthermore, the addition of water insoluble waxes (carnauba and bee wax) significantly retarded the release of the active ingredient. The addition of both waxes had a slight effect on drug release behavior. Nevertheless, the increase in incorporated waxes in all formulations could sustain the percentage of active ingredient release. In conclusion, wax-incorporated emulsion gel beads using a modified ionotropic gelation technique could be applied for the intragastric floating delivery and controlled release of functional food and nutraceutical products for their antioxidant and anticancer capacity. Full article

(This article belongs to the Special Issue Selected Papers from the 6th International Conference on Natural Products for Health and Beauty (NATPRO 6))

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14 pages, 4074 KiB

Open AccessArticle

Effects of Astaxanthin from Litopenaeus Vannamei on Carrageenan-Induced Edema and Pain Behavior in Mice

by Zulkiflee Kuedo, Anantita Sangsuriyawong, Wanwimol Klaypradit, Varomyalin Tipmanee and Pennapa Chonpathompikunlert

Molecules 2016, 21(3), 382; https://doi.org/10.3390/molecules21030382 - 19 Mar 2016

Cited by 28 | Viewed by 8677

Abstract

Carrageenan produces both inflammation and pain when injected in mouse paws via enhancement of reactive oxygen species formation. We have investigated an effect of astaxanthin extracted from Litopenaeus vannamei in carrageenan-induced mice paw edema and pain. The current study demonstrates interesting effects from [...] Read more.

Carrageenan produces both inflammation and pain when injected in mouse paws via enhancement of reactive oxygen species formation. We have investigated an effect of astaxanthin extracted from Litopenaeus vannamei in carrageenan-induced mice paw edema and pain. The current study demonstrates interesting effects from astaxanthin treatment in mice: an inhibition of paw edema induced in hind paw, an increase in mechanical paw withdrawal threshold and thermal paw withdrawal latency, and a reduction in the amount of myeloperoxidase enzyme and lipid peroxidation products in the paw. Furthermore the effect was comparable to indomethacin, a standard treatment for inflammation symptoms. Due to adverse effects of indomethacin on cardiovascular and gastrointestinal systems, our study suggests promising prospect of astaxanthin extract as an anti-inflammatory alternative against carrageenan-induced paw edema and pain behavior. Full article

(This article belongs to the Special Issue Selected Papers from the 6th International Conference on Natural Products for Health and Beauty (NATPRO 6))

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7 pages, 989 KiB

Open AccessArticle

A New Megastigmane Sesquiterpenoid from Zanthoxylum Schinifolium Sieb. et Zucc

by Linzhen Hu, Kongchao Wang, Zhenzhen Wang, Junjun Liu, Kaiping Wang, Jinwen Zhang, Zengwei Luo, Yongbo Xue, Yu Zhang and Yonghui Zhang

Molecules 2016, 21(3), 383; https://doi.org/10.3390/molecules21030383 - 19 Mar 2016

Cited by 6 | Viewed by 5714

Abstract

Zanthoxylum schinifolium Sieb. et Zucc. (Rutaceae), a dioecious shrub with hooked prickly branches, has been used as folk medicine for the treatment of the common cold, stomach ache, diarrhea, and jaundice in China, Korea, and Japan. In our phytochemical investigations on this genus, [...] Read more.

Zanthoxylum schinifolium Sieb. et Zucc. (Rutaceae), a dioecious shrub with hooked prickly branches, has been used as folk medicine for the treatment of the common cold, stomach ache, diarrhea, and jaundice in China, Korea, and Japan. In our phytochemical investigations on this genus, a new megastigmane sesquiterpenoid, which is referred to as schinifolenol A (1), was isolated from Z. schinifolium. The stereochemistry was characterized via the analyses of extensive spectra. The absolute configuration was established by the application of a modified Mosher’s experiment and assisted by a time-dependent density functional theory (TD-DFT) on calculated electronic circular dichroism (ECD). Bioactivity screenings showed that compound 1 exhibited a safe hypotoxicity and a better selectivity on anti-Kaposi’s sarcoma associated herpes virus (KSHV). Full article

(This article belongs to the Section Natural Products Chemistry)

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14 pages, 3921 KiB

Open AccessArticle

Casticin Inhibits A375.S2 Human Melanoma Cell Migration/Invasion through Downregulating NF-κB and Matrix Metalloproteinase-2 and -1

by Zih-Yun Wu, Jin-Cherng Lien, Yi-Ping Huang, Ching-Lung Liao, Jen-Jyh Lin, Ming-Jen Fan, Yang-Ching Ko, Yu-Ping Hsiao, Hsu-Feng Lu and Jing-Gung Chung

Molecules 2016, 21(3), 384; https://doi.org/10.3390/molecules21030384 - 19 Mar 2016

Cited by 26 | Viewed by 8669

Abstract

Casticin is one of the main components from Fructus Viticis, which is widely used as an anti-inflammatory agent. The mechanism of how casticin affects melanoma cell migration and invasion is still not well known. Here we studied the anti-metastasis effects of casticin [...] Read more.

Casticin is one of the main components from Fructus Viticis, which is widely used as an anti-inflammatory agent. The mechanism of how casticin affects melanoma cell migration and invasion is still not well known. Here we studied the anti-metastasis effects of casticin on A375.S2 melanoma cells by using a non-lethal concentration. First; we used an adhesion assay to test the A375.S2 cells’ adhesion ability after treatment with casticin. We next investigated the cell migration ability after casticin treatment by using a wound healing assay to prove that the migration of A375.S2 cells can be inhibited by casticin and double checked the results using the transwell-migration assay. The suppressive effects on matrix metalloproteinase-2; and -9 (MMP-2; and -9) activities were examined by gelatin zymography. Furthermore, western blotting was used to investigate the protein level changes in A375.S2 cells. We found that p-EGFR; Ras and p-ERK1/2 are decreased by casticin, indicating that casticin can down-regulate the migration and invasion ability of A375.S2 cells via the p-EGFR/Ras/p-ERK pathway. The NF-κB p65 and p-ERK levels in nuclear proteins are also decreased by treatment with casticin. An EMSA assay also discovered that the NF-κB p65 and DNA interaction is decreased. NF-κB p65 protein level was examined by immunofluorescence staining and also decreased. Our findings suggest that casticin has anti-metastatic potential by decreasing the invasiveness of A375.S2 cells. We also found that casticin suppressed A375.S2 cell proliferation and cell adhesion ability, but did not affect cell death, as examined using cytometry and a collagen adhesion assay. Based on these observations, casticin could be used as an inhibitor of migration and invasion of human melanoma cells in the future. Full article

(This article belongs to the Section Natural Products Chemistry)

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14 pages, 2200 KiB

Open AccessArticle

Deoxyelephantopin from Elephantopus scaber Inhibits HCT116 Human Colorectal Carcinoma Cell Growth through Apoptosis and Cell Cycle Arrest

by Chim Kei Chan, Gomathi Chan, Khalijah Awang and Habsah Abdul Kadir

Molecules 2016, 21(3), 385; https://doi.org/10.3390/molecules21030385 - 21 Mar 2016

Cited by 34 | Viewed by 8151

Abstract

Deoxyelephantopin (DET), one of the major sesquiterpene lactones derived from Elephantopus scaber was reported to possess numerous pharmacological functions. This study aimed to assess the apoptosis inducing effects and cell cycle arrest by DET followed by elucidation of the mechanisms underlying cell death [...] Read more.

Deoxyelephantopin (DET), one of the major sesquiterpene lactones derived from Elephantopus scaber was reported to possess numerous pharmacological functions. This study aimed to assess the apoptosis inducing effects and cell cycle arrest by DET followed by elucidation of the mechanisms underlying cell death in HCT116 cells. The anticancer activity of DET was evaluated by a MTT assay. Morphological and biochemical changes were detected by Hoescht 33342/PI and Annexin V/PI staining. The results revealed that DET and isodeoxyelephantopin (isoDET) could be isolated from the ethyl acetate fraction of E. scaber leaves via a bioassay-guided approach. DET induced significant dose- and time-dependent growth inhibition of HCT116 cells. Characteristics of apoptosis including nuclear morphological changes and externalization of phosphatidylserine were observed. DET also significantly resulted in the activation of caspase-3 and PARP cleavage. Additionally, DET induced cell cycle arrest at the S phase along with dose-dependent upregulation of p21 and phosphorylated p53 protein expression. DET dose-dependently downregulated cyclin D1, A2, B1, E2, CDK4 and CDK2 protein expression. In conclusion, our data showed that DET induced apoptosis and cell cycle arrest in HCT116 colorectal carcinoma, suggesting that DET has potential as an anticancer agent for colorectal carcinoma. Full article

(This article belongs to the Section Natural Products Chemistry)

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13 pages, 3091 KiB

Open AccessArticle

A Solvent-Free Surface Suspension Melt Technique for Making Biodegradable PCL Membrane Scaffolds for Tissue Engineering Applications

by Ratima Suntornnond, Jia An, Ajay Tijore, Kah Fai Leong, Chee Kai Chua and Lay Poh Tan

Molecules 2016, 21(3), 386; https://doi.org/10.3390/molecules21030386 - 21 Mar 2016

Cited by 4 | Viewed by 7268

Abstract

In tissue engineering, there is limited availability of a simple, fast and solvent-free process for fabricating micro-porous thin membrane scaffolds. This paper presents the first report of a novel surface suspension melt technique to fabricate a micro-porous thin membrane scaffolds without using any [...] Read more.

In tissue engineering, there is limited availability of a simple, fast and solvent-free process for fabricating micro-porous thin membrane scaffolds. This paper presents the first report of a novel surface suspension melt technique to fabricate a micro-porous thin membrane scaffolds without using any organic solvent. Briefly, a layer of polycaprolactone (PCL) particles is directly spread on top of water in the form of a suspension. After that, with the use of heat, the powder layer is transformed into a melted layer, and following cooling, a thin membrane is obtained. Two different sizes of PCL powder particles (100 µm and 500 µm) are used. Results show that membranes made from 100 µm powders have lower thickness, smaller pore size, smoother surface, higher value of stiffness but lower ultimate tensile load compared to membranes made from 500 µm powder. C2C12 cell culture results indicate that the membrane supports cell growth and differentiation. Thus, this novel membrane generation method holds great promise for tissue engineering. Full article

(This article belongs to the Special Issue Biomaterials and Bioprinting)

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17 pages, 2766 KiB

Open AccessArticle

Synthesis and Biological Evaluation of an ¹⁸Fluorine-Labeled COX Inhibitor—[¹⁸F]Fluorooctyl Fenbufen Amide—For Imaging of Brain Tumors

by Ying-Cheng Huang, Yu-Chia Chang, Chun-Nan Yeh and Chung-Shan Yu

Molecules 2016, 21(3), 387; https://doi.org/10.3390/molecules21030387 - 21 Mar 2016

Cited by 13 | Viewed by 5921

Abstract

Molecular imaging of brain tumors remains a great challenge, despite the advances made in imaging technology. An anti-inflammatory compound may be a useful tool for this purpose because there is evidence of inflammatory processes in brain tumor micro-environments. Fluorooctylfenbufen amide (FOFA) was prepared [...] Read more.

Molecular imaging of brain tumors remains a great challenge, despite the advances made in imaging technology. An anti-inflammatory compound may be a useful tool for this purpose because there is evidence of inflammatory processes in brain tumor micro-environments. Fluorooctylfenbufen amide (FOFA) was prepared from 8-chlorooctanol via treatment with potassium phthalimide, tosylation with Ts₂O, fluorination with KF under phase transfer catalyzed conditions, deprotection using aqueous hydrazine, and coupling with fenbufen. The corresponding radiofluoro product [¹⁸F]FOFA, had a final radiochemical yield of 2.81 mCi and was prepared from activated [¹⁸F]F⁻ (212 mCi) via HPLC purification and concentration. The radiochemical purity was determined to be 99%, and the specific activity was shown to exceed 22 GBq/μmol (EOS) based on decay-corrected calculations. Ex-vivo analysis of [¹⁸F]FOFA in plasma using HPLC showed that the agent had a half-life of 15 min. PET scanning showed significant accumulation of [¹⁸F]FOFA over tumor loci with reasonable contrast in C6-glioma bearing rats. These results suggest that this molecule is a promising agent for the visualization of brain tumors. Further investigations should focus on tumor micro-environments. Full article

(This article belongs to the Section Bioorganic Chemistry)

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11 pages, 3256 KiB

Open AccessArticle

Antibacterial Activity and Action Mechanism of the Essential Oil from Enteromorpha linza L. against Foodborne Pathogenic Bacteria

by Jayanta Kumar Patra and Kwang-Hyun Baek

Molecules 2016, 21(3), 388; https://doi.org/10.3390/molecules21030388 - 21 Mar 2016

Cited by 73 | Viewed by 8736

Abstract

Foodborne illness and disease caused by foodborne pathogenic bacteria is continuing to increase day by day and it has become an important topic of concern among various food industries. Many types of synthetic antibacterial agents have been used in food processing and food [...] Read more.

Foodborne illness and disease caused by foodborne pathogenic bacteria is continuing to increase day by day and it has become an important topic of concern among various food industries. Many types of synthetic antibacterial agents have been used in food processing and food preservation; however, they are not safe and have resulted in various health-related issues. Therefore, in the present study, essential oil from an edible seaweed, Enteromorpha linza (AEO), was evaluated for its antibacterial activity against foodborne pathogens, along with the mechanism of its antibacterial action. AEO at 25 mg/disc was highly active against Bacillus cereus (12.3–12.7 mm inhibition zone) and Staphylococcus aureus (12.7–13.3 mm inhibition zone). The minimum inhibitory concentration and minimum bactericidal concentration values of AEO ranged from 12.5–25 mg/mL. Further investigation of the mechanism of action of AEO revealed its strong impairing effect on the viability of bacterial cells and membrane permeability, as indicated by a significant increase in leakage of 260 nm absorbing materials and K⁺ ions from the cell membrane and loss of high salt tolerance. Taken together, these data suggest that AEO has the potential for use as an effective antibacterial agent that functions by impairing cell membrane permeability via morphological alternations, resulting in cellular lysis and cell death. Full article

(This article belongs to the Collection Recent Advances in Flavors and Fragrances)

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14 pages, 904 KiB

Open AccessArticle

Synthesis and Evaluation of Ester Derivatives of 10-Hydroxycanthin-6-one as Potential Antimicrobial Agents

by Fei Zhao, Jiang-Kun Dai, Dan Liu, Shi-Jun Wang and Jun-Ru Wang

Molecules 2016, 21(3), 390; https://doi.org/10.3390/molecules21030390 - 21 Mar 2016

Cited by 20 | Viewed by 5519

Abstract

As part of our continuing research on canthin-6-one antimicrobial agents, a new series of ester derivatives of 10-hydroxycanthin-6-one were synthesized using a simple and effective synthetic route. The structure of each compound was characterized by NMR, ESI-MS, FT-IR, UV, and elemental analysis. The [...] Read more.

As part of our continuing research on canthin-6-one antimicrobial agents, a new series of ester derivatives of 10-hydroxycanthin-6-one were synthesized using a simple and effective synthetic route. The structure of each compound was characterized by NMR, ESI-MS, FT-IR, UV, and elemental analysis. The antimicrobial activity of these compounds against three phytopathogenic fungi (Alternaria solani, Fusarium graminearum, and Fusarium solani) and four bacteria (Bacillus cereus, Bacillus subtilis, Ralstonia solanacearum, and Pseudomonas syringae) were evaluated using the mycelium linear growth rate method and micro-broth dilution method, respectively. The structure-activity relationship is discussed. Of the tested compounds, 4 and 7s displayed significant antifungal activity against F. graminearum, with inhibition rates of 100% at a concentration of 50 μg/mL. Compounds 5, 7s, and 7t showed the best inhibitory activity against all the tested bacteria, with minimum inhibitory concentrations (MICs) between 3.91 and 31.25 μg/mL. Thus, 7s emerged as a promising lead compound for the development of novel canthine-6-one antimicrobial agents. Full article

(This article belongs to the Special Issue Drug Design and Discovery: Principles and Applications)

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7 pages, 3025 KiB

Open AccessCommunication

Quorum Sensing Inhibitory Activity of Giganteone A from Myristica cinnamomea King against Escherichia coli Biosensors

by Yasodha Sivasothy, Thiba Krishnan, Kok-Gan Chan, Siti Mariam Abdul Wahab, Muhamad Aqmal Othman, Marc Litaudon and Khalijah Awang

Molecules 2016, 21(3), 391; https://doi.org/10.3390/molecules21030391 - 21 Mar 2016

Cited by 7 | Viewed by 5374

Abstract

Malabaricones A–C (1–3) and giganteone A (4) were isolated from the bark of Myristica cinnamomea King. Their structures were elucidated and characterized by means of NMR and MS spectral analyses. These isolates were evaluated for their anti-quorum sensing activity using quorum sensing biosensors, [...] Read more.

Malabaricones A–C (1–3) and giganteone A (4) were isolated from the bark of Myristica cinnamomea King. Their structures were elucidated and characterized by means of NMR and MS spectral analyses. These isolates were evaluated for their anti-quorum sensing activity using quorum sensing biosensors, namely Escherichia coli [pSB401] and Escherichia coli [pSB1075], whereby the potential of giganteone A (4) as a suitable anti-quorum sensing agent was demonstrated. Full article

(This article belongs to the Section Natural Products Chemistry)

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16 pages, 7889 KiB

Open AccessArticle

Trapa japonica Pericarp Extract Reduces LPS-Induced Inflammation in Macrophages and Acute Lung Injury in Mice

by Yon-Suk Kim, Jin-Woo Hwang, Jae-Hyuk Jang, Sangkeun Son, Il-Bok Seo, Jae-Hyun Jeong, Ee-Hwa Kim, Sang-Ho Moon, Byong-Tae Jeon and Pyo-Jam Park

Molecules 2016, 21(3), 392; https://doi.org/10.3390/molecules21030392 - 21 Mar 2016

Cited by 33 | Viewed by 7920

Abstract

In this study, we found that chloroform fraction (CF) from TJP ethanolic extract inhibited lipopolysaccharide (LPS)-induced production of nitric oxide (NO) and intracellular ROS in RAW264.7 cells. In addition, expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) genes was reduced, as [...] Read more.

In this study, we found that chloroform fraction (CF) from TJP ethanolic extract inhibited lipopolysaccharide (LPS)-induced production of nitric oxide (NO) and intracellular ROS in RAW264.7 cells. In addition, expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) genes was reduced, as evidenced by western blot. Our results indicate that CF exerts anti-inflammatory effects by down-regulating expression of iNOS and COX-2 genes through inhibition of MAPK (ERK, JNK and p38) and NF-κB signaling. Similarly we also evaluated the effects of CF on LPS-induced acute lung injury. Male Balb/c mice were pretreated with dexamethasone or CF 1 h before intranasal instillation of LPS. Eight hours after LPS administration, the inflammatory cells in the bronchoalveolar lavage fluid (BALF) were determined. The results indicated that CF inhibited LPS-induced TNF-α and IL-6 production in a dose dependent manner. It was also observed that CF attenuated LPS-induced lung histopathologic changes. In conclusion, these data demonstrate that the protective effect of CF on LPS-induced acute lung injury (ALI) in mice might relate to the suppression of excessive inflammatory responses in lung tissue. Thus, it can be suggested that CF might be a potential therapeutic agent for ALI. Full article

(This article belongs to the Section Medicinal Chemistry)

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Molecules, Volume 21, Issue 3 (March 2016) – 144 articles

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