Molecules

23 pages, 6786 KiB

Open AccessArticle

Evaluation of Lactic Acid Bacteria on the Inhibition of Vibrio parahaemolyticus Infection and Its Application to Food Systems

by Cheng-Chih Tsai^*, Yung-Hsien Hung and Lan-Chun Chou

Department of Food Science and Technology, HungKuang University, No. 1018, Sec. 6, Taiwan Boulevard, Shalu District, Taichung City 43302, Taiwan

Molecules 2018, 23(5), 1238; https://doi.org/10.3390/molecules23051238 - 22 May 2018

Cited by 11 | Viewed by 5563

Abstract

This study tested the effect of lactic acid bacteria (LAB) inhibition on Vibrio parahaemolyticus BCRC (Bioresource Collection and Research Center) 10806 and BCRC 12865 in a food model. MTT [3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assays indicated that Caco-2 cells were not damaged after a two-hour treatment [...] Read more.

This study tested the effect of lactic acid bacteria (LAB) inhibition on Vibrio parahaemolyticus BCRC (Bioresource Collection and Research Center) 10806 and BCRC 12865 in a food model. MTT [3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assays indicated that Caco-2 cells were not damaged after a two-hour treatment with lactic acid bacteria (LAB) and V. parahaemolyticus. The LAB cell culture and supernatant effectively inhibited the growth of V. parahaemolyticus in a food model. ELISA (Enzyme-linked immunosorbent assay) results indicated the significant inhibition of TNF-α; IL-1β; and IL-6; but Lactobacillus plantarum PM 222 and L. plantarum LP 735 did not significantly affect IL-8 levels. Real-time polymerase chain reaction (PCR) results indicated that LAB could inhibit the mRNA expression of proinflammatory cytokines IL-8; IL-6; and TNF-α; which were induced by V. parahaemolyticus. After rat-received LAB; the expression levels of TNF-α; IL-6; and IL-8 in the serum decreased significantly. In intestinal histology; the rat that received L. plantarum PM 222 and L. plantarum LP 010 was able to alleviate the intestinal villi damage caused by V. parahaemolyticus; which also helped reduce cell apoptosis. In conclusion; our results indicate that LAB can inhibit inflammatory responses caused by V. parahaemolyticus and can effectively inhibit the growth of V. parahaemolyticus in food products. Full article

(This article belongs to the Section Metabolites)

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9 pages, 1322 KiB

Open AccessArticle

MS/MS-Guided Isolation of Clarinoside, a New Anti-Inflammatory Pentalogin Derivative

by Coralie Audoin¹, Adam Zampalégré¹, Natacha Blanchet¹, Alexandre Giuliani^2,3

, Emmanuel Roulland⁴

, Olivier Laprévote^4,5 and Grégory Genta-Jouve^4,*

¹ Laboratoires Clarins, 5 rue Ampère, 95300 Pontoise, France

² DISCO Beamline, Synchrotron SOLEIL, 91192 Gif-sur-Yvette, France

³ UAR1008, CEPIA, INRA, 44316 Nantes, France

⁴ C-TAC, UMR 8638 CNRS, Faculté de Pharmacie de Paris, Université Paris Descartes, Sorbonne Paris Cité, 4 Avenue de l’Observatoire, 75006 Paris, France

⁵ Department of Biochemistry, Hôpital Européen Georges Pompidou, AH-HP, 75015 Paris, France

Molecules 2018, 23(5), 1237; https://doi.org/10.3390/molecules23051237 - 22 May 2018

Cited by 10 | Viewed by 5133

Abstract

Re-investigation of the chemical composition of the annual plant Mitracarpus scaber Zucc. led to the identification of clarinoside, a new pentalogin derivative containing a rare quinovose moiety, and the known compound harounoside. While the planar structure was fully determined using tandem mass spectrometry [...] Read more.

Re-investigation of the chemical composition of the annual plant Mitracarpus scaber Zucc. led to the identification of clarinoside, a new pentalogin derivative containing a rare quinovose moiety, and the known compound harounoside. While the planar structure was fully determined using tandem mass spectrometry (MS) and quantum mechanics (QM) calculations, the tridimensional structure was unravelled after isolation and NMR analysis. The absolute configuration was assigned by comparison of experimental and theoretical synchrotron radiation circular dichroism spectra. Both compounds were tested for anti-inflammatory activity, and compound 1 showed the ability to inhibit the production of interleukin-8 (Il-8) with an IC

_{50}

value of 9.17

μ

M. Full article

(This article belongs to the Special Issue Isolation and Structure Elucidation of Bioactive Compounds (Dedicated to the memory of the late Professor Charles D. Hufford))

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14 pages, 1734 KiB

Open AccessArticle

Mass Transfer in Osmotic Dehydration of Kiwiberry: Experimental and Mathematical Modelling Studies

by Michał Bialik¹, Artur Wiktor¹

, Piotr Latocha²

and Ewa Gondek^1,*

¹ Faculty of Food Sciences, Department of Food Engineering and Process Management, Warsaw University of Life Sciences, Nowoursynowska 159c, 02-776 Warsaw, Poland

² Faculty of Horticulture, Biotechnology and Landscape Architecture, Department of Environmental Protection, Warsaw University of Life Sciences, Nowoursynowska 159, 02-776 Warsaw, Poland

Molecules 2018, 23(5), 1236; https://doi.org/10.3390/molecules23051236 - 22 May 2018

Cited by 26 | Viewed by 5560

Abstract

The aim of this study was to analyze the impact of osmotic solutions and temperature on the osmotic dehydration (OD) of two cultivars of kiwiberry. OD was carried out in sucrose, xylitol and maltitol solutions at 30 °C and 50 °C, respectively. The [...] Read more.

The aim of this study was to analyze the impact of osmotic solutions and temperature on the osmotic dehydration (OD) of two cultivars of kiwiberry. OD was carried out in sucrose, xylitol and maltitol solutions at 30 °C and 50 °C, respectively. The process of osmotic dehydration was described by the means of water loss (WL), solid gain (SG), weight reduction (WR), and water content changes. Moreover, dehydration was described by mathematical models often used in the literature. The highest WL, WR and SG values were observed for samples treated by xylitol and maltitol at 50 °C. The statistical analysis of the mathematical modelling of the process showed that in most cases, the Peleg’s equation exhibits better fitting for the experimental data. Full article

(This article belongs to the Collection Preanalytical Methods for Natural Products Production)

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10 pages, 1609 KiB

Open AccessArticle

Study on the Discrimination between Citri Reticulatae Pericarpium Varieties Based on HS-SPME-GC-MS Combined with Multivariate Statistical Analyses

by Yuying Zheng

, Xuan Zeng

, Wei Peng, Zhong Wu and Weiwei Su^*

Guangdong Engineering & Technology Research Center for Quality and Efficacy Reevaluation of Post-Market Traditional Chinese Medicine, Guangdong Key Laboratory of Plant Resources, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China

Molecules 2018, 23(5), 1235; https://doi.org/10.3390/molecules23051235 - 22 May 2018

Cited by 51 | Viewed by 5293

Abstract

Citri reticulatae pericarpium (CRP), the dried pericarps of Citrus reticulata Blanco and its cultivars, has been widely used in drugs and foods in China for centuries. In this study, an accurate and feasible analytical method based on HS-SPME-GC-MS coupled with multivariate statistical analyses [...] Read more.

Citri reticulatae pericarpium (CRP), the dried pericarps of Citrus reticulata Blanco and its cultivars, has been widely used in drugs and foods in China for centuries. In this study, an accurate and feasible analytical method based on HS-SPME-GC-MS coupled with multivariate statistical analyses was developed to comprehensively compare volatile compounds of pericarps derived from Citrus reticulata “Chachi” (“Guangchenpi” in Chinese, GCP) and other cultivars of Citrus reticulata Blanco (“Chenpi” in Chinese, CP). Principal component analysis, hierarchical cluster analysis, and orthogonal partial least-squares-discrimination analysis were performed to extract meaningful attributes from volatile profiles based on GC-MS data. Results indicated that samples from GCP and CP could easily be differentiated, and seven potential chemical markers were screened for the quality control of CRP. This study illuminated the volatile profile in CRP, and provides a practical method for the authentication of CRP varieties. Full article

(This article belongs to the Section Analytical Chemistry)

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12 pages, 1850 KiB

Open AccessFeature PaperArticle

Photothermal Effectiveness of Magnetite Nanoparticles: Dependence upon Particle Size Probed by Experiment and Simulation

by Robert J. G. Johnson, Jonathan D. Schultz and Benjamin J. Lear^*

Department of Chemistry, The Pennsylvania State University, University Park, PA 16802, USA

Molecules 2018, 23(5), 1234; https://doi.org/10.3390/molecules23051234 - 22 May 2018

Cited by 24 | Viewed by 5422

Abstract

The photothermal effect of nanoparticles has proven efficient for driving diverse physical and chemical processes; however, we know of no study addressing the dependence of efficacy on nanoparticle size. Herein, we report on the photothermal effect of three different sizes (5.5 nm, 10 [...] Read more.

The photothermal effect of nanoparticles has proven efficient for driving diverse physical and chemical processes; however, we know of no study addressing the dependence of efficacy on nanoparticle size. Herein, we report on the photothermal effect of three different sizes (5.5 nm, 10 nm and 15 nm in diameter) of magnetite nanoparticles (MNP) driving the decomposition of poly(propylene carbonate) (PPC). We find that the chemical effectiveness of the photothermal effect is positively correlated with particle volume. Numerical simulations of the photothermal heating of PPC supports this observation, showing that larger particles are able to heat larger volumes of PPC for longer periods of time. The increased heating duration is likely due to increased heat capacity, which is why the volume of the particle functions as a ready guide for the photothermal efficacy. Full article

(This article belongs to the Special Issue Photothermal Agents in Therapy)

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16 pages, 889 KiB

Open AccessReview

Molecular Docking Studies of HIV-1 Resistance to Reverse Transcriptase Inhibitors: Mini-Review

by Olga Tarasova^*

, Vladimir Poroikov

and Alexander Veselovsky

Institute of Biomedical Chemistry, 10 Building 8, Pogodinskaya st., Moscow 119121, Russia

Molecules 2018, 23(5), 1233; https://doi.org/10.3390/molecules23051233 - 21 May 2018

Cited by 41 | Viewed by 8587

Abstract

Currently, millions of people are living with human immunodeficiency virus type 1 (HIV-1), which causes acquired immunodeficiency syndrome. However, the spread of the HIV-1 resistance to antiviral agents is the major problem in the antiretroviral therapy and medical management of HIV-infected patients. HIV-1 [...] Read more.

Currently, millions of people are living with human immunodeficiency virus type 1 (HIV-1), which causes acquired immunodeficiency syndrome. However, the spread of the HIV-1 resistance to antiviral agents is the major problem in the antiretroviral therapy and medical management of HIV-infected patients. HIV-1 reverse transcriptase (RT) is one of the key viral targets for HIV-1 inhibition. Therefore, the studies on the combatting the HIV resistance that occurs due to the structural changes in RT, are in great demand. This work aims to provide an overview of the state-of-the-art molecular docking approaches applied to the studies of the HIV-1 resistance, associated with RT structure changes. We have reviewed recent studies using molecular docking with mutant forms of RT. The work discusses the modifications of molecular docking, which have been developed to find the novel molecules active against resistance mutants of RT and/or recombinant strains of HIV-1. The perspectives of the existing algorithms of molecular docking to the studies on molecular mechanisms of resistance and selection of the correct binding poses for the reverse transcriptase inhibitors are discussed. Full article

(This article belongs to the Special Issue Recent Trends on Enzymes Inhibitors and Activators in Drug Research)

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18 pages, 3568 KiB

Open AccessArticle

Evaluation of Transition Metal Complexes of Benzimidazole-Derived Scaffold as Promising Anticancer Chemotherapeutics

by Afzal Hussain¹, Mohamed F. AlAjmi¹, Md. Tabish Rehman¹

, Azmat Ali Khan²

, Perwez Alam Shaikh¹ and Rais Ahmad Khan^3,*

¹ Department of Pharmacognosy, College of Pharmacy, King Saud University, P.O. Box 2457, 11451 Riyadh, Saudi Arabia

² Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, 11451 Riyadh, Saudi Arabia

³ Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, 11451 Riyadh, Saudi Arabia

Molecules 2018, 23(5), 1232; https://doi.org/10.3390/molecules23051232 - 21 May 2018

Cited by 43 | Viewed by 5539

Abstract

Three new transition metal complexes, Cu(II) 1, Co(II) 2, and Zn(II) 3 with ligand “bimnap” derived from 1-methyl-2-aminobenzimidazole and 2-hydroxynapthaldehyde were synthesized and characterized. The structure of the ligand was determined by single X-ray crystallography. All the three complexes, 1– [...] Read more.

Three new transition metal complexes, Cu(II) 1, Co(II) 2, and Zn(II) 3 with ligand “bimnap” derived from 1-methyl-2-aminobenzimidazole and 2-hydroxynapthaldehyde were synthesized and characterized. The structure of the ligand was determined by single X-ray crystallography. All the three complexes, 1–3, were examined for the mode of interaction with biomolecule viz., calf thymus-DNA (CT-DNA) using various spectroscopic methods. The nuclease activity was performed against pBR322 DNA that exhibited concentration-dependent degradation of the nucleic acid. The mechanism of DNA cleavage was studied by the electrophoretic pattern in the presence of the radical scavengers. Also, the complexes 1–3 were analyzed for groove binding affinity. Moreover, in vitro cytotoxicities of the complexes 1–3 were tested against the five human cancer cell lines, i.e., HeLa, SK-MEL-1, HepG2, HT108, and MDA-MB 231. Also, the cell adhesion and migration properties upon treatment of cell lines with complexes 1–3, and consequently, their cell death pathway via apoptosis and necrosis were analyzed. Further, complexes 1–3 were studied in vivo for their toxicities and tolerabilities in mice. In sum, the complexes 1–3 showed merits of an effective anticancer agent in cell lines–based study while minor side effects were observed in vivo. Full article

(This article belongs to the Section Inorganic Chemistry)

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14 pages, 2700 KiB

Open AccessArticle

Density Functional Theory Applied to Excited State Intramolecular Proton Transfer in Imidazole-, Oxazole-, and Thiazole-Based Systems

by Fabricio De Carvalho, Maurício D. Coutinho Neto, Fernando H. Bartoloni^*

and Paula Homem-de-Mello^*

Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Santo André, São Paulo 5001, Brazil

Molecules 2018, 23(5), 1231; https://doi.org/10.3390/molecules23051231 - 21 May 2018

Cited by 15 | Viewed by 5482

Abstract

Excited state intramolecular proton transfer (ESIPT) is a photoinduced process strongly associated to hydrogen bonding within a molecular framework. In this manuscript, we computed potential energy data using Time Dependent Density Functional Theory (TDDFT) for triphenyl-substituted heterocycles, which evidenced an energetically favorable proton [...] Read more.

Excited state intramolecular proton transfer (ESIPT) is a photoinduced process strongly associated to hydrogen bonding within a molecular framework. In this manuscript, we computed potential energy data using Time Dependent Density Functional Theory (TDDFT) for triphenyl-substituted heterocycles, which evidenced an energetically favorable proton transfer on the excited state (i.e., ESIPT) but not on the ground state. Moreover, we describe how changes on heterocyclic functionalities, based on imidazole, oxazole, and thiazole systems, affect the ESIPT process that converts an enolic species to a ketonic one through photon-induced proton transfer. Structural and photophysical data were obtained theoretically by means of density functional theory (DFT) calculations and contrasted for the three heterocyclics. Different functionals were used, but B3LYP was the one that adequately predicted absorption data. It was observed that the intramolecular hydrogen bond is strengthened in the excited state, supporting the occurrence of ESIPT. Finally, it was observed that, with the formation of the excited state, there is a decrease in electronic density at the oxygen atom that acts as proton donor, while there is a substantial increase in the corresponding density at the nitrogen atom that serves as proton acceptor, thus, indicating that proton transfer is indeed favored after photon absorption. Full article

(This article belongs to the Special Issue Theoretical Excited-State Chemistry: New Developments and Cutting-Edge Applications)

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22 pages, 1865 KiB

Open AccessArticle

Quality Traits of “Cannabidiol Oils”: Cannabinoids Content, Terpene Fingerprint and Oxidation Stability of European Commercially Available Preparations

by Radmila Pavlovic^1,2, Giorgio Nenna³, Lorenzo Calvi², Sara Panseri^4,*, Gigliola Borgonovo⁵, Luca Giupponi^1,2

, Giuseppe Cannazza⁶

and Annamaria Giorgi^1,2

¹ CRC-Ge.S.Di.Mont.—Centre for Applied Studies in the Sustainable Management and Protection of the Mountain Environment, CRC-Ge.S.Di.Mont.—Università degli Studi di Milano, Via Morino 8, Edolo, 25048 Brescia, Italy

² Department of Agricultural and Environmental Sciences—Production, Landscape, Agroenergy, Università degli Studi di Milano, Via Celoria 2, 20133 Milan, Italy

³ UPFARM-UTIFAR—The Professional Union of Pharmacists for Orphan Medicines; Piazza Duca d'Aosta, 14, 20124 Milan, Italy

⁴ Department of Health, Animal Science and Food Safety, Università degli Studi di Milano, Via Celoria 10, 20133 Milan, Italy

⁵ Dipartimento di Scienze per gli Alimenti, la Nutrizione e l’Ambiente, Università degli Studi di Milano, Via Celoria 2, 20133 Milan, Italy

⁶ Dipartimento di Scienze della Vita, Università di Modena e Reggio Emilia, Via Campi 103, 41121 Modena, Italy

Molecules 2018, 23(5), 1230; https://doi.org/10.3390/molecules23051230 - 20 May 2018

Cited by 166 | Viewed by 31614

Abstract

Cannabidiol (CBD)-based oil preparations are becoming extremely popular, as CBD has been shown to have beneficial effects on human health. CBD-based oil preparations are not unambiguously regulated under the European legislation, as CBD is not considered as a controlled substance. This means that [...] Read more.

Cannabidiol (CBD)-based oil preparations are becoming extremely popular, as CBD has been shown to have beneficial effects on human health. CBD-based oil preparations are not unambiguously regulated under the European legislation, as CBD is not considered as a controlled substance. This means that companies can produce and distribute CBD products derived from non-psychoactive hemp varieties, providing an easy access to this extremely advantageous cannabinoid. This leaves consumers with no legal quality guarantees. The objective of this project was to assess the quality of 14 CBD oils commercially available in European countries. An in-depth chemical profiling of cannabinoids, terpenes and oxidation products was conducted by means of GC-MS and HPLC-Q-Exactive-Orbitrap-MS in order to improve knowledge regarding the characteristics of CBD oils. Nine out of the 14 samples studied had concentrations that differed notably from the declared amount, while the remaining five preserved CBD within optimal limits. Our results highlighted a wide variability in cannabinoids profile that justifies the need for strict and standardized regulations. In addition, the terpenes fingerprint may serve as an indicator of the quality of hemp varieties, while the lipid oxidation products profile could contribute in evaluation of the stability of the oil used as milieu for CBD rich extracts. Full article

(This article belongs to the Special Issue Qualitative and Quantitative Analysis of Bioactive Natural Products 2018)

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15 pages, 4218 KiB

Open AccessArticle

Plasma Pharmacokinetic Determination of Canagliflozin and Its Metabolites in a Type 2 Diabetic Rat Model by UPLC-MS/MS

by Song-tao Dong¹, Hui-min Niu¹, Yin Wu², Jia-lei Jiang¹, Ying Li², Kun-yu Jiang¹, Xin Wang¹, Mao-fan Zhang¹, Ming-feng Han¹ and Sheng-nan Meng^1,*

¹ Department of Pharmaceutics, School of Pharmacy, China Medical University, Shenyang 110001, China

² Department of Pharmaceutics, School of Pharmacy, Hebei Medical University, Shijiazhuang 050017, China

Molecules 2018, 23(5), 1229; https://doi.org/10.3390/molecules23051229 - 20 May 2018

Cited by 19 | Viewed by 6135

Abstract

Canagliflozin is a novel, orally selective inhibitor of sodium-dependent glucose co-transporter-2 (SGLT2) for the treatment of patients with type 2 diabetes mellitus. In this study, a sensitive and efficient UPLC-MS/MS method for the quantification of canagliflozin and its metabolites in rat plasma was [...] Read more.

Canagliflozin is a novel, orally selective inhibitor of sodium-dependent glucose co-transporter-2 (SGLT2) for the treatment of patients with type 2 diabetes mellitus. In this study, a sensitive and efficient UPLC-MS/MS method for the quantification of canagliflozin and its metabolites in rat plasma was established and applied to pharmacokinetics in a type 2 diabetic rat model. We firstly investigated the pharmacokinetic changes of canagliflozin and its metabolites in type 2 diabetic rats in order to use canagliflozin more safely, reasonably and effectively. We identified three types of O-glucuronide metabolites (M5, M7 and M17), two kinds of oxidation metabolites (M8 and M9) and one oxidation and glucuronide metabolite (M16) using API 5600 triple-TOF-MS/MS. Following liquid–liquid extraction by tert-butyl methyl ether, chromatographic separation of canagliflozin and its metabolites were performed on a Waters XBridge BEH C18 column (100 × 2.1 mm, 2.5 μm) using 0.1% acetonitrile–formic acid (75:15, v/v) as the mobile phase at a flow rate of 0.7 mL/min. Selected ion monitoring transitions of m/z 462.00→191.10, 451.20→153.10, 638.10→191.10 and 478.00→267.00 were chosen to quantify canagliflozin, empagliflozin (IS), O-glucuronide metabolites (M5, M7 and M17), and oxidation metabolites (M9) using an API 5500-triple-MS/MS in the positive electrospray ionization mode. The validation of the method was found to be of sufficient specificity, accuracy and precision. The pathological condition of diabetes could result in altered pharmacokinetic behaviors of canagliflozin and its metabolites. The pharmacokinetic parameters (AUC_0–t, AUC_0–∞, CL_z/F, and V_z/F) of canagliflozin were significantly different between the CTRL and DM group rats (p < 0.05 or p < 0.01), which may subsequently cause different therapeutic effects. Full article

(This article belongs to the Collection Advances in Liquid Separation Techniques for Food and Pharmaceutical Analysis)

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15 pages, 2750 KiB

Open AccessArticle

Cyclodextrins: Assessing the Impact of Cavity Size, Occupancy, and Substitutions on Cytotoxicity and Cholesterol Homeostasis

by Lajos Szente¹, Ashutosh Singhal^2,3

, Andras Domokos⁴

and Byeongwoon Song^2,3,*

¹ Cyclolab Cyclodextrin Research and Development Laboratory Ltd., H-1097 Budapest, Hungary

² Department of Microbiology, Immunology, and Physiology, Meharry Medical College, Nashville, TN 37208, USA

³ Center for AIDS Health Disparities Research, Meharry Medical College, Nashville, TN 37208, USA

⁴ Department of Chemistry, University of California-Davis, Davis, CA 95616, USA

Molecules 2018, 23(5), 1228; https://doi.org/10.3390/molecules23051228 - 20 May 2018

Cited by 93 | Viewed by 8354

Abstract

Cyclodextrins (CDs) are cyclic oligosaccharides; the most common CDs contain six, seven, or eight glucose units called α-CDs, β-CDs, and γ-CDs, respectively. The use of CDs in biomedical research is increasing due to their ability to interact with membrane lipids as well as [...] Read more.

Cyclodextrins (CDs) are cyclic oligosaccharides; the most common CDs contain six, seven, or eight glucose units called α-CDs, β-CDs, and γ-CDs, respectively. The use of CDs in biomedical research is increasing due to their ability to interact with membrane lipids as well as a wide variety of poorly water-soluble molecules. We assessed the impact of CD cavity size, occupancy, and substitutions on cytotoxicity and cholesterol homeostasis. The potency of CD-mediated cytotoxicity was in the order of β-CDs, α-CDs, and γ-CDs. Substitutions with hydroxypropyl or carboxymethyl group attenuated cytotoxicity compared with the native CDs, whereas CDs substituted with methyl groups exhibited cytotoxicity that was similar to that of the native CDs. The lipid components in blood exerted remarkable hemolysis-alleviating effects in methyl-β-CD-induced hemolysis. Occupancy of the CD cavity with cholesterol or a structurally related lipid molecule abrogated the cytotoxic capacity of the CDs. Interestingly, hydroxypropyl-γ-CD (HPγCD) was able to reduce intracellular cholesterol accumulation in Niemann–Pick disease type C (NPC) patient-derived fibroblasts as efficiently as HPβCD. Proteomic study indicated that HPβCD and HPγCD treatments altered the expression pattern of cellular proteins, suggesting that some of the CD-induced cellular proteins may play an important function in modulating intracellular cholesterol homeostasis. Full article

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15 pages, 1214 KiB

Open AccessArticle

The Microencapsulation of Maqui (Aristotelia chilensis (Mol.) Stuntz) Juice by Spray-Drying and Freeze-Drying Produces Powders with Similar Anthocyanin Stability and Bioaccessibility

by Carolina Fredes¹

, Camila Becerra¹, Javier Parada²

and Paz Robert^1,*

¹ Departamento de Ciencia de los Alimentos y Tecnología Química, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Sergio Livingstone Pohlhammer 1007, Independencia 8380492, Chile

² Institute of Food Science and Technology, Faculty of Agricultural Sciences, Austral University of Chile, Valdivia 5090000, Chile

Molecules 2018, 23(5), 1227; https://doi.org/10.3390/molecules23051227 - 20 May 2018

Cited by 67 | Viewed by 6307

Abstract

The microencapsulation of maqui juice by spray-drying and freeze-drying was studied as a strategy to protect anthocyanins in new food formulations in order to improve the anthocyanin retention before consumption and the bioaccessibility. It is well known that the encapsulation method affects both [...] Read more.

The microencapsulation of maqui juice by spray-drying and freeze-drying was studied as a strategy to protect anthocyanins in new food formulations in order to improve the anthocyanin retention before consumption and the bioaccessibility. It is well known that the encapsulation method affects both the shape and size of powders, being assumed that undefined forms of freeze-drying powders might affect their stability due to the high permeability to oxygen. The objective of this study was to compare the microencapsulation of maqui juice by spray-drying and freeze-drying, evaluating the stability of specific anthocyanins in yogurt and after in vitro digestion. Results indicated that most relevant differences between spray-drying and freeze-drying powders were the morphology and particle size that affect their solubility (70.4–59.5%) when they were reconstituted in water. Nevertheless these differences did not affect the stability of anthocyanins as other research have proposed. Both encapsulation methods generated powders with a high stability of 3-O-monoglycosylated anthocyanins in yogurt (half-life values of 75–69 days for delphinidin-3-sambubioside). Furthermore, no significant differences in the bioaccessibility of anthocyanins between maqui juice powders (44.1–43.8%) were found. In conclusion, the microencapsulation of maqui juice by freeze-drying is as effective as spray-drying to produce new value-added food formulations with stable anthocyanins. Full article

(This article belongs to the Special Issue Advances in Anthocyanin Research 2018)

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29 pages, 343 KiB

Open AccessFeature PaperReview

Nutraceuticals in Periodontal Health: A Systematic Review on the Role of Vitamins in Periodontal Health Maintenance

by Alfonso Varela-López¹

, María D. Navarro-Hortal², Francesca Giampieri¹

, Pedro Bullón³

, Maurizio Battino¹

and José L. Quiles^2,*

¹ Dipartimento di Scienze Cliniche Specialistiche ed Odontostomatologiche (DISCO)-Sez. Biochimica, Facoltà di Medicina, Università Politecnica delle Marche, 60131 Ancona, Italy

² Department of Physiology, Institute of Nutrition and Food Technology “Jose Mataix”, Biomedical Research Center, University of Granada, Avda. Conocimiento s/n, 18100 Armilla, Granada, Spain

³ Department of Stomalogy, Dental School, University of Sevilla, C/Avicena s.n., 41009 Sevilla, Spain

Molecules 2018, 23(5), 1226; https://doi.org/10.3390/molecules23051226 - 20 May 2018

Cited by 53 | Viewed by 10296

Abstract

Periodontal disease, a relevant public health problem worldwide, is generally considered a common pathology of elderly people. In this respect, there is agreement about that nutritional status may be a modifying factor in the progression and healing of the periodontal tissues. Vitamins have [...] Read more.

Periodontal disease, a relevant public health problem worldwide, is generally considered a common pathology of elderly people. In this respect, there is agreement about that nutritional status may be a modifying factor in the progression and healing of the periodontal tissues. Vitamins have been recommended as nutraceuticals for prevention and treatment of some pathological conditions, such as cardiovascular diseases, obesity or cancer. Thus, a systematic approach to determining how the different vitamin type could ameliorate periodontal risks or improve periodontal health is necessary to further the understanding of the potential benefits and risks of vitamins supplementation use. For this, a systematic review of English-written literature in PubMed until February 2018, which included both human and animal research on the relationship of each vitamin with periodontal disease, was conducted. Among all the analyzed vitamins those with antioxidant capacity and effects on immune system seem to be useful for prevention or improvement of periodontal disease, as well as those implicated in bone metabolism. In the first case, there are quite information in favor of various vitamins, mainly vitamin C, that is the most studied. In the second case, vitamin D seems to have the most relevant role. Full article

(This article belongs to the Special Issue Nutraceuticals and Their Medicinal Importance)

9 pages, 2992 KiB

Open AccessArticle

Conformational Aspects of the O-acetylation of C-tetra(phenyl)calixpyrogallol[4]arene

by José Luis Casas-Hinestroza and Mauricio Maldonado^*

Departamento de Química, Facultad de Ciencias, Universidad Nacional de Colombia-sede Bogotá, Carrera 30 # 45-03, Bogotá 111321, Columbia

Molecules 2018, 23(5), 1225; https://doi.org/10.3390/molecules23051225 - 20 May 2018

Cited by 11 | Viewed by 4085

Abstract

Reaction between pyrogallol and benzaldehyde results in a conformational mixture of C-tetra(phenyl)pyrogallol[4]arene (crown and chair). The conformer mixture was separated using crystallization procedures and the structures were determined using FTIR, ¹H-NMR, and ¹³C-NMR. O-acetylation of C-tetra(phenyl)pyrogallol[4]arene (chair) with [...] Read more.

Reaction between pyrogallol and benzaldehyde results in a conformational mixture of C-tetra(phenyl)pyrogallol[4]arene (crown and chair). The conformer mixture was separated using crystallization procedures and the structures were determined using FTIR, ¹H-NMR, and ¹³C-NMR. O-acetylation of C-tetra(phenyl)pyrogallol[4]arene (chair) with acetic anhydride, in pyridine results in the formation of dodecaacetyl-tetra(phenyl)pyrogallol[4]arene. The structure was determined using ¹H-NMR and ¹³C-NMR finding that the product maintains the conformation of the starting conformer. On the other hand, the O-acetylation reaction of C-tetra(phenyl)pirogallol[4]arene (crown) under same conditions proceeded efficiently, and its structure was determined using ¹H-NMR and ¹³C-NMR. Dynamic ¹H-NMR of acetylated pyrogallolarene was studied by means of variable temperature in DMSO-d₆ solution, and it revealed that two conformers are formed in the solution. Boat conformations for acetylated pyrogallolarene showed a slow interconversion at room temperature. Full article

(This article belongs to the Section Organic Chemistry)

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17 pages, 2038 KiB

Open AccessArticle

Calculation of the Surface Tension of Ordinary Organic and Ionic Liquids by Means of a Generally Applicable Computer Algorithm Based on the Group-Additivity Method

by Rudolf Naef^1,*

and William E. Acree²

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

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

Molecules 2018, 23(5), 1224; https://doi.org/10.3390/molecules23051224 - 20 May 2018

Cited by 29 | Viewed by 4969

Abstract

The calculation of the surface tension of ordinary organic and ionic liquids, based on a computer algorithm applying a refined group-additivity method, is presented. The refinement consists of the complete breakdown of the molecules into their constituting atoms, further distinguishing them by their [...] Read more.

The calculation of the surface tension of ordinary organic and ionic liquids, based on a computer algorithm applying a refined group-additivity method, is presented. The refinement consists of the complete breakdown of the molecules into their constituting atoms, further distinguishing them by their immediate neighbour atoms and bond constitution. The evaluation of the atom-groups’ contributions was carried out by means of a fast Gauss-Seidel fitting method, founded upon the experimental data of 1893 compounds from literature. The result has been tested for plausibility using a 10-fold cross-validation (cv) procedure. The direct calculation and the cv test proved the applicability of the present method by the close similarity and excellent goodness of fit R² and Q² of 0.9039 and 0.8823, respectively. The respective standard deviations are ±1.99 and ±2.16 dyn/cm. Some correlation peculiarities have been observed in a series of ordinary and ionic liquids with homologous alkyl chains, as well as with di- and trihydroxy-groups-containing liquids, which have been discussed in detail, exhibiting the limit of the present method. Full article

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18 pages, 2250 KiB

Open AccessArticle

d-Amino Acid Peptide Residualizing Agents for Protein Radioiodination: Effect of Aspartate for Glutamate Substitution

by Marek Pruszynski^1,2,*

, Choong Mo Kang^1,3, Eftychia Koumarianou^1,4

, Ganesan Vaidyanathan¹ and Michael R. Zalutsky^1,*

¹ Department of Radiology, Duke University Medical Center, Durham, NC 27710, USA

² Present address: Institute of Nuclear Chemistry and Technology, 03-195 Warsaw, Poland

³ Present address: Korea Institute of Radiological and Medical Sciences, Seoul 01812, Korea

⁴ Present address: Laboratory for Translational and Molecular Imaging, Duke-National University of Singapore Medical School, Singapore 169857, Singapore

Molecules 2018, 23(5), 1223; https://doi.org/10.3390/molecules23051223 - 20 May 2018

Cited by 7 | Viewed by 3869

Abstract

The residualizing prosthetic agent N^ε-(3-[^*I]iodobenzoyl)-Lys⁵-N^α-maleimido-Gly¹-d-GEEEK ([^*I]IB-Mal-d-GEEEK) showed promise for the radioiodination of monoclonal antibodies (mAbs) that bind to internalizing molecular targets. Although enhanced tumor uptake was [...] Read more.

The residualizing prosthetic agent N^ε-(3-[^*I]iodobenzoyl)-Lys⁵-N^α-maleimido-Gly¹-d-GEEEK ([^*I]IB-Mal-d-GEEEK) showed promise for the radioiodination of monoclonal antibodies (mAbs) that bind to internalizing molecular targets. Although enhanced tumor uptake was achieved in these studies, elevated kidney accumulation also was observed, particularly with low-molecular-weight, single-domain antibody fragments (sdAbs). Here, we developed an analogous agent (IB-Mal-d-GDDDK), in which glutamate residues (E) were replaced with aspartates (D) to determine whether this modification could decrease renal uptake. [¹²⁵I]IB-Mal-d-GDDDK and [¹³¹I]IB-Mal-d-GEEEK were synthesized with similar radiochemical yields (60–80%) and coupled to the anti-HER2 sdAb 5F7 at 50–60% efficiency. Paired-label internalization assays in vitro indicated similar levels of intracellular activity residualization in HER2-expressing BT474M1 cells for [¹²⁵I]IB-Mal-d-GDDDK-5F7 and [¹³¹I]IB-Mal-d-GEEEK-5F7. A paired-label biodistribution comparison of the two labeled conjugates was performed in mice with HER2-expressing SKOV-3 xenografts, and the results of this study indicated that renal uptake at 1 h was 127.5 ± 18.7% ID/g and 271.4 ± 66.6% ID/g for [¹²⁵I]IB-Mal-d-GDDDK-5F7 and [¹³¹I]IB-Mal-d-GEEEK-5F7, respectively. The tumor uptake of the two radioconjugates was not significantly different. These results demonstrate that substitution of E with D in the IB-Mal-d-GEEEK construct reduced kidney accumulation of the sdAb. However, renal activity levels need to be reduced further if d-amino acid derived prosthetic agents are to be of practical value for labeling low molecular weight biomolecules such as sdAbs. Full article

(This article belongs to the Section Bioorganic Chemistry)

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12 pages, 938 KiB

Open AccessArticle

Isolation and Antimicrobial Activity of Coumarin Derivatives from Fruits of Peucedanum luxurians Tamamsch

by Jarosław Widelski¹, Simon Vlad Luca^1,2, Adrianna Skiba¹, Ioanna Chinou³, Laurence Marcourt⁴, Jean-Luc Wolfender⁴

and Krystyna Skalicka-Wozniak^1,*

¹ Department of Pharmacognosy with Medicinal Plant Unit, Medical University of Lublin, Chodzki, 120-093 Lublin, Poland

² Department of Pharmacognosy, “Grigore T. Popa” University of Medicine and Pharmacy, 16 Universitatii Street, 700115 Iasi, Romania

³ Department of Pharmacognosy and Chemistry of Natural Products, School of Pharmacy, University of Athens, Zografou, 15771 Athens, Greece

⁴ School of Pharmaceutical Sciences, EPGL, University of Geneva, University of Lausanne, CMU, 1, Rue Michel Servet, 1211 Geneva 4, Switzerland

Molecules 2018, 23(5), 1222; https://doi.org/10.3390/molecules23051222 - 20 May 2018

Cited by 42 | Viewed by 6209

Abstract

As a continuation of searching for phytoconstituents that act as promising agents for antimicrobial therapy, rare coumarins were isolated from fruits of Peucedanum luxurians and tested. In a first step, the content of major compounds in the aerial parts and fruits of P. [...] Read more.

As a continuation of searching for phytoconstituents that act as promising agents for antimicrobial therapy, rare coumarins were isolated from fruits of Peucedanum luxurians and tested. In a first step, the content of major compounds in the aerial parts and fruits of P. luxurians were compared. The results clearly showed that the fruits with dichloromethane as a solvent yielded, in most cases, higher concentrations of almost all the analyzed coumarins than the aerial parts, with peucedanin detected as the most abundant compound with a concentration of 4563.94 ± 3.35 mg/100 g. Under this perspective, the dichloromethane extract from the fruits of P. luxurians was further submitted to high performance countercurrent chromatography with a mixture of n-hexane, ethyl acetate, methanol, and water 6:5:6:5 (v/v). Combination of HPCCC and prep-HPLC yielded 6′,7′-dihydroxybergamottin (1), officinalin (2), stenocarpin isobutyrate (3), officinalin isobutyrate (4), 8-methoxypeucedanin (5), and peucedanin (6). Isolated compounds were tested against several Gram-positive and Gram-negative bacteria strains. 6′,7′-Dihydroxybergamottin, peucedanin, and officinalin isobutyrate appeared to be the most active against all tested bacteria strains with minimum inhibitory concentration (MIC) values between 1.20 and 4.80 mg/mL. To the best of our knowledge, this is the first report about countercurrent isolation of mentioned coumarins, as well as the first information about their antimicrobial activity. Full article

(This article belongs to the Section Natural Products Chemistry)

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23 pages, 13494 KiB

Open AccessArticle

1,2,6-Thiadiazinones as Novel Narrow Spectrum Calcium/Calmodulin-Dependent Protein Kinase Kinase 2 (CaMKK2) Inhibitors

by Christopher R. M. Asquith^1,2,*

, Paulo H. Godoi³

, Rafael M. Couñago^3,4, Tuomo Laitinen⁵

, John W. Scott^6,7,8

, Christopher G. Langendorf⁶, Jonathan S. Oakhill^6,7, David H. Drewry¹

, William J. Zuercher^1,9

, Panayiotis A. Koutentis¹⁰

, Timothy M. Willson¹ and Andreas S. Kalogirou^10,11,*

¹ Structural Genomics Consortium, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA

² Department of Pharmacology, University of North Carolina at Chapel Hill, NC 27599, USA

³ Structural Genomics Consortium, Universidade Estadual de Campinas-UNICAMP, Campinas, São Paulo 13083-886, Brazil

⁴ Center for Molecular and Genetic Engineering (CBMEG), University of Campinas (UNICAMP), Cidade Universitária Zeferino Vaz, Avenida Cândido Rondon 400, P. O. Box 6010, 13083-875 Campinas, São Paulo 13083-886, Brazil

⁵ School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, 70211 Kuopio, Finland

⁶ St Vincent’s Institute and Department of Medicine, University of Melbourne, 41 Victoria Parade, Fitzroy 3065, Australia

⁷ Mary MacKillop Institute for Health Research, Australian Catholic University, 215 Spring Street, Melbourne 3000, Australia

⁸ The Florey Institute of Neuroscience and Mental Health, Parkville 3052, Australia

⁹ Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA

¹⁰ Department of Chemistry, University of Cyprus, P. O. Box 20537, 1678 Nicosia, Cyprus

¹¹ Department of Life Sciences, School of Sciences, European University Cyprus, 6 Diogenis Str., Engomi, P. O. Box 22006, 1516 Nicosia, Cyprus

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Molecules 2018, 23(5), 1221; https://doi.org/10.3390/molecules23051221 - 19 May 2018

Cited by 25 | Viewed by 7794

Abstract

We demonstrate for the first time that 4H-1,2,6-thiadiazin-4-one (TDZ) can function as a chemotype for the design of ATP-competitive kinase inhibitors. Using insights from a co-crystal structure of a 3,5-bis(arylamino)-4H-1,2,6-thiadiazin-4-one bound to calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2), several [...] Read more.

We demonstrate for the first time that 4H-1,2,6-thiadiazin-4-one (TDZ) can function as a chemotype for the design of ATP-competitive kinase inhibitors. Using insights from a co-crystal structure of a 3,5-bis(arylamino)-4H-1,2,6-thiadiazin-4-one bound to calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2), several analogues were identified with micromolar activity through targeted displacement of bound water molecules in the active site. Since the TDZ analogues showed reduced promiscuity compared to their 2,4-dianilinopyrimidine counter parts, they represent starting points for development of highly selective kinase inhibitors. Full article

(This article belongs to the Special Issue Focusing on Sulfur in Medicinal Chemistry)

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15 pages, 3571 KiB

Open AccessArticle

Broad-Spectrum Antimicrobial Activity and Low Cytotoxicity against Human Cells of a Peptide Derived from Bovine α_S1-Casein

by Juncai Hou^1,*, Zhijing Liu¹, Songsong Cao¹, Haimei Wang¹, Chenggang Jiang², Muhammad Altaf Hussain¹ and Shiyue Pang¹

¹ Key Laboratory of Dairy Science, Northeast Agricultural University, College of Food Science, Harbin 150030, China

² Harbin Veterinary Research Institute, CAAS, Harbin 150001, China

Molecules 2018, 23(5), 1220; https://doi.org/10.3390/molecules23051220 - 19 May 2018

Cited by 21 | Viewed by 5246

Abstract

The primary objective of this study was to improve our understanding of the antimicrobial mechanism of protein-derived peptides and to provide evidence for protein-derived peptides as food bio-preservatives by examining the antimicrobial activities, low cytotoxicity, stabilities, and mechanism of Cp1 (LRLKKYKVPQL). In this [...] Read more.

The primary objective of this study was to improve our understanding of the antimicrobial mechanism of protein-derived peptides and to provide evidence for protein-derived peptides as food bio-preservatives by examining the antimicrobial activities, low cytotoxicity, stabilities, and mechanism of Cp1 (LRLKKYKVPQL). In this study, the protein-derived peptide Cp1 was synthesized from bovine α_S1-casein, and its potential use as a food biopreservative was indicated by the higher cell selectivity shown by 11-residue peptide towards bacterial cells than human RBCs. It also showed broad-spectrum antimicrobial activity, with minimum inhibitory concentrations (MICs) of 64–640 μM against both gram-positive and gram-negative bacteria. The peptide had low hemolytic activity (23.54%, 512 μM) as well as cytotoxicity. The results of fluorescence spectroscopy, flow cytometry, and electron microscopy experiments indicated that Cp1 exerted its activity by permeabilizing the microbial membrane and destroying cell membrane integrity. We found that Cp1 had broad-spectrum antimicrobial activity, low hemolytic activity, and cytotoxicity. The results also revealed that Cp1 could cause cell death by permeabilizing the cell membrane and disrupting membrane integrity. Overall, the findings presented in this study improve our understanding of the antimicrobial potency of Cp1 and provided evidence of the antimicrobial mechanisms of Cp1. The peptide Cp1 could have potential applications as a food biopreservative. Full article

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25 pages, 2024 KiB

Open AccessFeature PaperReview

Targeting Protein Quality Control Mechanisms by Natural Products to Promote Healthy Ageing

by Sophia Wedel¹, Maria Manola²

, Maria Cavinato¹

, Ioannis P. Trougakos^2,*

and Pidder Jansen-Dürr^1,*

¹ Institute for Biomedical Aging Research, University of Innsbruck, 6020 Innsbruck, Austria

² Department of Cell Biology and Biophysics, Faculty of Biology, National and Kapodistrian University of Athens, 15784 Athens, Greece

Molecules 2018, 23(5), 1219; https://doi.org/10.3390/molecules23051219 - 19 May 2018

Cited by 31 | Viewed by 8234

Abstract

Organismal ageing is associated with increased chance of morbidity or mortality and it is driven by diverse molecular pathways that are affected by both environmental and genetic factors. The progression of ageing correlates with the gradual accumulation of stressors and damaged biomolecules due [...] Read more.

Organismal ageing is associated with increased chance of morbidity or mortality and it is driven by diverse molecular pathways that are affected by both environmental and genetic factors. The progression of ageing correlates with the gradual accumulation of stressors and damaged biomolecules due to the time-dependent decline of stress resistance and functional capacity, which eventually compromise cellular homeodynamics. As protein machines carry out the majority of cellular functions, proteome quality control is critical for cellular functionality and is carried out through the curating activity of the proteostasis network (PN). Key components of the PN are the two main degradation machineries, namely the ubiquitin-proteasome and autophagy-lysosome pathways along with several stress-responsive pathways, such as that of nuclear factor erythroid 2-related factor 2 (Nrf2), which mobilises cytoprotective genomic responses against oxidative and/or xenobiotic damage. Reportedly, genetic or dietary interventions that activate components of the PN delay ageing in evolutionarily diverse organisms. Natural products (extracts or pure compounds) represent an extraordinary inventory of highly diverse structural scaffolds that offer promising activities towards meeting the challenge of increasing healthspan and/or delaying ageing (e.g., spermidine, quercetin or sulforaphane). Herein, we review those natural compounds that have been found to activate proteostatic and/or anti-stress cellular responses and hence have the potential to delay cellular senescence and/or in vivo ageing. Full article

(This article belongs to the Special Issue Plant Derived Natural Products and Age Related Diseases)

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13 pages, 1864 KiB

Open AccessArticle

Sterol Composition of Clinically Relevant Mucorales and Changes Resulting from Posaconazole Treatment

by Christoph Müller¹, Thomas Neugebauer², Patrizia Zill¹, Cornelia Lass-Flörl²

, Franz Bracher¹

and Ulrike Binder^2,*

¹ Department of Pharmacy-Center for Drug Research, Ludwig-Maximilians University of Munich, Butenandtstr. 5-13, 81377 Munich, Germany

² Department of Hygiene, Microbiology and Public Health, Division of Hygiene and Medical Microbiology, Medical University Innsbruck, Schöpfstr. 41, 6020 Innsbruck, Austria

Molecules 2018, 23(5), 1218; https://doi.org/10.3390/molecules23051218 - 19 May 2018

Cited by 20 | Viewed by 4754

Abstract

Mucorales are fungi with increasing importance in the clinics. Infections take a rapidly progressive course resulting in high mortality rates. The ergosterol biosynthesis pathway and sterol composition are of interest, since they are targeted by currently applied antifungal drugs. Nevertheless, Mucorales often exhibit [...] Read more.

Mucorales are fungi with increasing importance in the clinics. Infections take a rapidly progressive course resulting in high mortality rates. The ergosterol biosynthesis pathway and sterol composition are of interest, since they are targeted by currently applied antifungal drugs. Nevertheless, Mucorales often exhibit resistance to these drugs, resulting in therapeutic failure. Here, sterol patterns of six clinically relevant Mucorales (Lichtheimia corymbifera, Lichtheimia ramosa, Mucor circinelloides, Rhizomucor pusillus, Rhizopus arrhizus, and Rhizopus microsporus) were analysed in a targeted metabolomics fashion after derivatization by gas chromatography-mass spectrometry. Additionally, the effect of posaconazole (POS) treatment on the sterol pattern of R. arrhizus was evaluated. Overall, fifteen different sterols were detected with species dependent variations in the total and relative sterol amount. Sterol analysis from R. arrhizus hyphae confronted with sublethal concentrations of posaconazole revealed the accumulation of 14-methylergosta-8,24-diene-3,6-diol, which is a toxic sterol that was previously only detected in yeasts. Sterol content and composition were further compared to the well-characterized pathogenic mold Aspergillus fumigatus. This work contributes to a better understanding of the ergosterol biosynthesis pathway of Mucorales, which is essential to improve antifungal efficacy, the identification of targets for novel drug design, and to investigate the combinatorial effects of drugs targeting this pathway. Full article

(This article belongs to the Special Issue Chemical Biology of Sterols, Triterpenoids and Other Natural Products: A Themed Issue in Honor of Professor W. David Nes on the Occasion of His 65th Birthday)

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11 pages, 2232 KiB

Open AccessArticle

Synthesis and Insecticidal Activity of Mesoionic Pyrido[1,2-α]pyrimidinone Derivatives Containing a Neonicotinoid Moiety

by Jianke Pan, Lu Yu, Dengyue Liu and Deyu Hu^*

State Key Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Guizhou University, Huaxi District, Guiyang 550025, China

Molecules 2018, 23(5), 1217; https://doi.org/10.3390/molecules23051217 - 19 May 2018

Cited by 13 | Viewed by 6079

Abstract

Mesoionic pyrido[1,2-α]pyrimidinone derivatives containing a neonicotinoid moiety were designed, synthesized, and evaluated for their insecticidal activity. Some of the title compounds showed remarkable insecticidal properties against Aphis craccivora. Compound I13 exhibited satisfactory insecticidal activity against A. craccivora. Meanwhile, label-free proteomics analysis [...] Read more.

Mesoionic pyrido[1,2-α]pyrimidinone derivatives containing a neonicotinoid moiety were designed, synthesized, and evaluated for their insecticidal activity. Some of the title compounds showed remarkable insecticidal properties against Aphis craccivora. Compound I13 exhibited satisfactory insecticidal activity against A. craccivora. Meanwhile, label-free proteomics analysis of compound I13 treatment identified a total of 821 proteins. Of these, 35 proteins were up-regulated, whereas 108 proteins were down-regulated. Differential expressions of these proteins reflected a change in cellular structure and metabolism. Full article

(This article belongs to the Section Medicinal Chemistry)

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8 pages, 2492 KiB

Open AccessArticle

Improved Synthesis of N-Methylcadaverine

by Kayla N. Anderson, Shiva Moaven, Daniel K. Unruh

, Anthony F. Cozzolino^*

and John C. D’Auria^*

Department of Chemistry and Biochemistry, Texas Tech University, Box 41061, Lubbock, TX 79409-1061, USA

Molecules 2018, 23(5), 1216; https://doi.org/10.3390/molecules23051216 - 19 May 2018

Cited by 1 | Viewed by 5652

Abstract

Alkaloids compose a large class of natural products, and mono-methylated polyamines are a common intermediate in their biosynthesis. In order to evaluate the role of selectively methylated natural products, synthetic strategies are needed to prepare them. Here, N-methylcadaverine is prepared in 37.3% [...] Read more.

Alkaloids compose a large class of natural products, and mono-methylated polyamines are a common intermediate in their biosynthesis. In order to evaluate the role of selectively methylated natural products, synthetic strategies are needed to prepare them. Here, N-methylcadaverine is prepared in 37.3% yield in three steps. The alternative literature two-step strategy resulted in reductive deamination to give N-methylpiperidine as determined by the single crystal structure. A straightforward strategy to obtain the mono-alkylated aliphatic diamine, cadaverine, which avoids potential side-reactions, is demonstrated. Full article

(This article belongs to the Special Issue Chemical Biology of Sterols, Triterpenoids and Other Natural Products: A Themed Issue in Honor of Professor W. David Nes on the Occasion of His 65th Birthday)

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13 pages, 3591 KiB

Open AccessArticle

In Vitro Estrogenic and Breast Cancer Inhibitory Activities of Chemical Constituents Isolated from Rheum undulatum L.

by Dahae Lee^1,†, SeonJu Park^2,†, Sungyoul Choi³, Seung Hyun Kim^2,* and Ki Sung Kang^3,*

¹ School of Pharmacy, Sungkyunkwan University, Suwon 16419, Korea

² College of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Incheon 21983, Korea

³ College of Korean Medicine, Gachon University, Seongnam 13120, Korea

^† These authors contributed equally to this work.

Molecules 2018, 23(5), 1215; https://doi.org/10.3390/molecules23051215 - 18 May 2018

Cited by 21 | Viewed by 5586

Abstract

We investigated the estrogenic and breast cancer inhibitory activities of chemical constituents isolated from Rhei undulati Rhizoma (roots of Rheum undulatum L.), which is used as a laxative, an anti-inflammatory, and an anti-blood stagnation agent. Estrogen-like activity was studied using the well characterized [...] Read more.

We investigated the estrogenic and breast cancer inhibitory activities of chemical constituents isolated from Rhei undulati Rhizoma (roots of Rheum undulatum L.), which is used as a laxative, an anti-inflammatory, and an anti-blood stagnation agent. Estrogen-like activity was studied using the well characterized E-screen assay in estrogen receptor (ER)-positive MCF-7 cells. The mechanism underlying the breast cancer inhibitory activity of the compounds was studied using human ER-negative MDA-MB-231 and ER-positive MCF-7 cells. The activation of apoptosis pathway-related proteins was investigated by western blotting, using extracts of R. undulatum prepared in three solvent conditions (EX1, EX2, and EX3). The R. undulatum chemical constituents (compounds 1–3) showed estrogen-like activity in the concentration range of 10 to 50 μM, by increasing the proliferation of human ER-positive MCF-7 cells. These effects were attenuated by co-treatment with 100 nM fulvestrant, an ER antagonist. Compounds 1–3 decreased the viability of MCF-7 cells in a concentration-dependent manner. Compounds 1 (aloe emodin) and 2 (rhapontigenin) induced mitochondria-independent apoptosis by activating the caspase-8 pathway, whereas the cytotoxic effect of compound 3 (chrysophanol 1-O-β-d-glucopyranoside) was mediated through the mitochondria-dependent apoptotic pathway. Full article

(This article belongs to the Special Issue Nutraceuticals and Their Medicinal Importance)

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8 pages, 916 KiB

Open AccessFeature PaperCommunication

Antioxidants from the Brown Alga Dictyopteris undulata

by Momochika Kumagai^1,2,3, Keisuke Nishikawa²

, Hiroshi Matsuura⁴, Taiki Umezawa^1,5

, Fuyuhiko Matsuda^1,5 and Tatsufumi Okino^1,5,*

¹ Graduate School of Environmental Science, Hokkaido University, Sapporo 060-0810, Japan

² Department of Chemistry, Graduate School of Science, Osaka City University, Sumiyoshi-ku, Osaka 558-8585, Japan

³ Japan Food Research Laboratories, Ibaraki, Osaka 567-0085, Japan

⁴ National Institute of Technology, Asahikawa College, Asahikawa 071-8142, Japan

⁵ Faculty of Environmental Earth Science, Hokkaido University, Sapporo 060-0810, Japan

Molecules 2018, 23(5), 1214; https://doi.org/10.3390/molecules23051214 - 18 May 2018

Cited by 18 | Viewed by 5837

Abstract

An investigation of anti-oxidative compounds from the brown alga Dictyopteris undulata has led to the isolation and identification of isozonarol, isozonarone, chromazonarol, zonaroic acid and isozonaroic acid. Their structures were identified by comparison of MS and NMR spectra. Full NMR assignment and absolute [...] Read more.

An investigation of anti-oxidative compounds from the brown alga Dictyopteris undulata has led to the isolation and identification of isozonarol, isozonarone, chromazonarol, zonaroic acid and isozonaroic acid. Their structures were identified by comparison of MS and NMR spectra. Full NMR assignment and absolute configuration of isozonaroic acid are described. Isozonarol showed the most potent 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity among the compounds isolated. Full article

(This article belongs to the Collection Bioactive Compounds)

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23 pages, 1164 KiB

Open AccessReview

Echinacoside, an Inestimable Natural Product in Treatment of Neurological and other Disorders

by Jingjing Liu^1,†, Lingling Yang^1,†, Yanhong Dong¹, Bo Zhang¹ and Xueqin Ma^1,2,*

¹ Department of Pharmaceutical Analysis, School of Pharmacy, Ningxia Medical University, 1160 Shenli Street, Yinchuan 750004, China

² Key Laboratory of Hui Ethnic Medicine Modernization, Ministry of Education, Ningxia Medical University, 1160 Shenli Street, Yinchuan 750004, China

^† These authors contributed equally to this work.

Molecules 2018, 23(5), 1213; https://doi.org/10.3390/molecules23051213 - 18 May 2018

Cited by 76 | Viewed by 8214

Abstract

Echinacoside (ECH), a natural phenylethanoid glycoside, was first isolated from Echinacea angustifolia DC. (Compositae) sixty years ago. It was found to possess numerous pharmacologically beneficial activities for human health, especially the neuroprotective and cardiovascular effects. Although ECH showed promising potential for treatment of [...] Read more.

Echinacoside (ECH), a natural phenylethanoid glycoside, was first isolated from Echinacea angustifolia DC. (Compositae) sixty years ago. It was found to possess numerous pharmacologically beneficial activities for human health, especially the neuroprotective and cardiovascular effects. Although ECH showed promising potential for treatment of Parkinson’s and Alzheimer’s diseases, some important issues arose. These included the identification of active metabolites as having poor bioavailability in prototype form, the definite molecular signal pathways or targets of ECH with the above effects, and limited reliable clinical trials. Thus, it remains unresolved as to whether scientific research can reasonably make use of this natural compound. A systematic summary and knowledge of future prospects are necessary to facilitate further studies for this natural product. The present review generalizes and analyzes the current knowledge on ECH, including its broad distribution, different preparation technologies, poor pharmacokinetics and kinds of therapeutic uses, and the future perspectives of its potential application. Full article

(This article belongs to the Collection Bioactive Compounds)

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13 pages, 1084 KiB

Open AccessArticle

Novel Imidazole Aldoximes with Broad-Spectrum Antimicrobial Potency against Multidrug Resistant Gram-Negative Bacteria

by Mirjana Skočibušić^1,*

, Renata Odžak²

, Alma Ramić³

, Tomislav Smolić^3,†, Tomica Hrenar³ and Ines Primožič^3,*

¹ Department of Biology, Faculty of Science, University of Split, R. Boškovića 33, HR-21 000 Split, Croatia

² Department of Chemistry, Faculty of Science, University of Split, R. Boškovića 33, HR-21 000 Split, Croatia

³ Department of Chemistry, Faculty of Science, University of Zagreb, Horvatovac 102a, HR-10 000 Zagreb, Croatia

^† Present Address: Cargill Food Ingredients & Bio-Industrial, Cargill 84 Havenstraat, Vilvoorde, Vlaams-Brabant 1800, Belgium.

Molecules 2018, 23(5), 1212; https://doi.org/10.3390/molecules23051212 - 18 May 2018

Cited by 12 | Viewed by 5164

Abstract

In the search for a new class of potential antimicrobial agents, five novel N-substituted imidazole 2-aldoximes and their six quaternary salts were evaluated. The antimicrobial activity was assessed against a panel of representative Gram-positive and Gram-negative bacteria, including multidrug resistant bacteria. All [...] Read more.

In the search for a new class of potential antimicrobial agents, five novel N-substituted imidazole 2-aldoximes and their six quaternary salts were evaluated. The antimicrobial activity was assessed against a panel of representative Gram-positive and Gram-negative bacteria, including multidrug resistant bacteria. All compounds demonstrated potent in vitro activity against the tested microorganisms, with MIC values ranging from 6.25 to 50.0 μg/mL. Among the tested compounds, two quaternary compounds (N-but-3-enyl- and meta- (10) or para- N-chlorobenzyl (11) imidazolium 2-aldoximes) displayed the most potent and broad-spectrum activity against both Gram-positive and Gram-negative bacterial strains. The broth microdilution assay was also used to investigate the antiresistance efficacy of the both most active compounds against a set of Enterobacteriaceae isolates carried a multiple extended-spectrum β-lactamases (ESBLs) in comparison to eight clinically relevant antibiotics. N-but-3-enyl-N-meta-chlorobenzyl imidazolium 2-aldoxime was found to possess promising antiresistance efficacy against a wide range of β-lactamases producing strains (MIC 2.0 to 16.0 μg/mL). Best results for that compound were obtained against Escherichia coli and Enterobacter cloacae producing multiple β-lactamases form A and C molecular classes, which were 32- and 128-fold more potent than ceftazidime and cefotaxime, respectively. To visualize the results, principal component analysis was used as an additional classification tool. The mixture of ceftazidime and compound 10 (3 μg:2 μg) showed a strong activity and lower the necessary amount (up to 40-fold) of 10 against five of ESBL-producing isolates (MIC ≤ 1 µg/mL). Full article

(This article belongs to the Section Medicinal Chemistry)

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11 pages, 1073 KiB

Open AccessCommunication

β-Phenylalanine Ester Synthesis from Stable β-Keto Ester Substrate Using Engineered ω-Transaminases

by Oliver Buß^1,*,†

, Moritz Voss^2,†, André Delavault¹

, Pascal Gorenflo¹, Christoph Syldatk¹, Uwe Bornscheuer²

and Jens Rudat¹

¹ Institute of Process Engineering in Life Sciences, Section II: Technical Biology, Karlsruhe Institute of Technology, 76021 Karlsruhe, Germany

² Department of Biotechnology & Enzyme Catalysis, University of Greifswald, Institute of Biochemistry, Felix-Hausdorff-Str. 4, 17487 Greifswald, Germany

^† These authors contributed equally to this work.

Molecules 2018, 23(5), 1211; https://doi.org/10.3390/molecules23051211 - 18 May 2018

Cited by 19 | Viewed by 7977

Abstract

The successful synthesis of chiral amines from ketones using ω-transaminases has been shown in many cases in the last two decades. In contrast, the amination of β-keto acids is a special and relatively new challenge, as they decompose easily in aqueous solution. To [...] Read more.

The successful synthesis of chiral amines from ketones using ω-transaminases has been shown in many cases in the last two decades. In contrast, the amination of β-keto acids is a special and relatively new challenge, as they decompose easily in aqueous solution. To avoid this, transamination of the more stable β-keto esters would be an interesting alternative. For this reason, ω-transaminases were tested in this study, which enabled the transamination of the β-keto ester substrate ethyl benzoylacetate. Therefore, a ω-transaminase library was screened using a coloring o-xylylenediamine assay. The ω-transaminase mutants 3FCR_4M and ATA117 11Rd show great potential for further engineering experiments aiming at the synthesis of chiral (S)- and (R)-β-phenylalanine esters. This alternative approach resulted in the conversion of 32% and 13% for the (S)- and (R)-enantiomer, respectively. Furthermore, the (S)-β-phenylalanine ethyl ester was isolated by performing a semi-preparative synthesis. Full article

(This article belongs to the Special Issue Frontier in Biocatalysis for Organic Synthesis)

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9 pages, 2673 KiB

Open AccessArticle

Hydroxysafflor Yellow A Attenuates Lipopolysaccharide-Induced Neurotoxicity and Neuroinflammation in Primary Mesencephalic Cultures

by Tian Wang^1,2,†, Yu-Xin Ding^1,2,†, Jie He³, Cheng-Jun Ma³, Yue Zhao³, Zhen-Hua Wang³ and Bing Han^3,*

¹ Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), School of Pharmacy, Ministry of Education, Yantai University, Yantai 264005, China

² Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai 264005, China

³ Center of Mitochondria and Healthy Aging, School of Life Science, Yantai University, Yantai 264005, China

^† These authors contributed equally to this work.

Molecules 2018, 23(5), 1210; https://doi.org/10.3390/molecules23051210 - 18 May 2018

Cited by 11 | Viewed by 3978

Abstract

Lipopolysaccharide (LPS)-induced neuroinflammation triggers and accelerates the pathogenesis of Parkinson’s disease (PD). Carthamus tinctorius L., a traditional Chinese medicine, has been widely used for the treatment of cerebrovascular disease. Hydroxysafflor Yellow A (HSYA) is an active component of C. tinctorius. The purpose [...] Read more.

Lipopolysaccharide (LPS)-induced neuroinflammation triggers and accelerates the pathogenesis of Parkinson’s disease (PD). Carthamus tinctorius L., a traditional Chinese medicine, has been widely used for the treatment of cerebrovascular disease. Hydroxysafflor Yellow A (HSYA) is an active component of C. tinctorius. The purpose of this study was to investigate whether HSYA could attenuate LPS-induced neurotoxicity and neuroinflammation in primary mesencephalic cultures. Cell viability was measured by MTT and LDH assays. The number of tyrosine hydroxylase (TH) positive neuron was observed by immunohistochemistry. NF-κB p65 and iNOS expressions were evaluated with western blotting method. Pro-inflammatory cytokines including IL-1β and TNF-α were determined by ELISA kits. Nitric oxide (NO) content in the culture medium was assayed. The results showed that HSYA treatment significantly attenuated the LPS-induced dopaminergic neurons damage. HSYA partially inhibited the expressions of NF-κB p65 and iNOS. Furthermore, HSYA decreased the content of IL-1β, TNF-α and NO in the supernatants. Taken together, these results suggest that HSYA exerts protective effects on LPS-induced neurotoxicity in dopaminergic neurons and the mechanisms may be associated with the inhibition of inflammatory response. Full article

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17 pages, 2274 KiB

Open AccessArticle

Novel Structural Insight into Inhibitors of Heme Oxygenase-1 (HO-1) by New Imidazole-Based Compounds: Biochemical and In Vitro Anticancer Activity Evaluation

by Khaled F. Greish¹

, Loredana Salerno^2,*

, Reem Al Zahrani¹, Emanuele Amata²

, Maria N. Modica²

, Giuseppe Romeo²

, Agostino Marrazzo²

, Orazio Prezzavento², Valeria Sorrenti²

, Antonio Rescifina²

, Giuseppe Floresta^2,3,*

, Sebastiano Intagliata⁴

and Valeria Pittalà²

¹ Department of Molecular Medicine, College of Medicine and Medical Sciences, Princess Al-Jawhara Centre for Molecular Medicine, Arabian Gulf University, Manama 329, Bahrain

² Department of Drug Sciences, University of Catania, V.le A. Doria 6, 95125 Catania, Italy

³ Department of Chemical Sciences, University of Catania, V.le A. Doria, 95125 Catania, Italy

⁴ Department of Medicinal Chemistry, College of Pharmacy, University of Florida, Gainesville, FL 32610, USA

Molecules 2018, 23(5), 1209; https://doi.org/10.3390/molecules23051209 - 18 May 2018

Cited by 43 | Viewed by 5738

Abstract

In this paper, the design, synthesis, and molecular modeling of a new azole-based HO-1 inhibitors was reported, using compound 1 as a lead compound, in which an imidazole moiety is linked to a hydrophobic group by means of an ethanolic spacer. The tested [...] Read more.

In this paper, the design, synthesis, and molecular modeling of a new azole-based HO-1 inhibitors was reported, using compound 1 as a lead compound, in which an imidazole moiety is linked to a hydrophobic group by means of an ethanolic spacer. The tested compounds showed a good inhibitor activity and possessed IC₅₀ values in the micromolar range. These results were obtained by targeting the hydrophobic western region. Molecular modeling studies confirmed a consolidated binding mode in which the nitrogen of the imidazolyl moiety coordinated the heme ferrous iron, meanwhile the hydrophobic groups were located in the western region of HO-1 binding pocket. Moreover, the new compounds were screened for in silico ADME-Tox properties to predict drug-like behavior with convincing results. Finally, the in vitro antitumor activity profile of compound 1 was investigated in different cancer cell lines and nanomicellar formulation was synthesized with the aim of improving compound’s 1 water solubility. Finally, compound 1 was tested in melanoma cells in combination with doxorubicin showing interesting synergic activity. Full article

(This article belongs to the Section Medicinal Chemistry)

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Molecules, Volume 23, Issue 5 (May 2018) – 253 articles

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