Molecules

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3 pages, 146 KiB

Open AccessEditorial

Special Issue: Chemoinformatics

by Peter Willett

Molecules 2016, 21(4), 535; https://doi.org/10.3390/molecules21040535 - 22 Apr 2016

Cited by 3 | Viewed by 4722

Abstract

Chemoinformatics techniques were originally developed for the construction and searching of large archives of chemical structures but they were soon applied to problems in drug discovery and are now playing an increasingly important role in many additional areas of chemistry. This Special Issue [...] Read more.

Chemoinformatics techniques were originally developed for the construction and searching of large archives of chemical structures but they were soon applied to problems in drug discovery and are now playing an increasingly important role in many additional areas of chemistry. This Special Issue contains seven original research articles and four review articles that provide an introduction to several aspects of this rapidly developing field. Full article

(This article belongs to the Special Issue Chemoinformatics)

Research

Jump to: Editorial, Review, Other

7 pages, 492 KiB

Open AccessArticle

Physicochemical Properties of Defatted Rambutan (Nephelium lappaceum) Seed Flour after Alkaline Treatment

by Jirawat Eiamwat, Sorada Wanlapa and Sukit Kampruengdet

Molecules 2016, 21(4), 364; https://doi.org/10.3390/molecules21040364 - 31 Mar 2016

Cited by 14 | Viewed by 6694

Abstract

Rambutan seeds were subjected to SC-CO₂ extraction at 35 MPa, 45 °C to obtain defatted rambutan seed flour. Its physicochemical properties before and after treatment with alakali solution using 0.075 N NaOH were investigated. Alkali-treated flour had a significant increment in bulk [...] Read more.

Rambutan seeds were subjected to SC-CO₂ extraction at 35 MPa, 45 °C to obtain defatted rambutan seed flour. Its physicochemical properties before and after treatment with alakali solution using 0.075 N NaOH were investigated. Alkali-treated flour had a significant increment in bulk density, swelling power, water adsorption capacity, emulsion capacity and stability but a reduction in turbidity, solubility and oil absorption capacity. Pasting measurements showed peak viscosity, breakdown, setback and final viscosity increased significantly for the alkali-treated flour, while pasting temperature decreased. The alkaline treatment decreased the least gelation concentration, but increased the apparent viscosity. 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, 759 KiB

Open AccessCommunication

Secondary Metabolites from the Deep-Sea Derived Fungus Acaromyces ingoldii FS121

by Xiao-Wei Gao, Hong-Xin Liu, Zhang-Hua Sun, Yu-Chan Chen, Yu-Zhi Tan and Wei-Min Zhang

Molecules 2016, 21(4), 371; https://doi.org/10.3390/molecules21040371 - 29 Mar 2016

Cited by 35 | Viewed by 5880

Abstract

Activity-guided isolation of the fermentation broth of the deep-sea derived fungus Acaromyces ingoldii FS121, which was obtained from the China South Sea, yielded a new naphtha-[2,3-b]pyrandione analogue, acaromycin A (1) and a new thiazole analogue, acaromyester A (2 [...] Read more.

Activity-guided isolation of the fermentation broth of the deep-sea derived fungus Acaromyces ingoldii FS121, which was obtained from the China South Sea, yielded a new naphtha-[2,3-b]pyrandione analogue, acaromycin A (1) and a new thiazole analogue, acaromyester A (2), as well as the known compound (+)-cryptosporin (3). Their structures, including absolute configurations, were determined by extensive spectroscopic analysis and electronic circular dichroism (ECD) spectra. Compounds 1–3 were evaluated for in vitro growth inhibitory activities against four tumor cell lines (MCF-7, NCI-H460, SF-268 and HepG-2), wherein compounds 1 and 3 exhibited considerable growth inhibitory effects, with IC₅₀ values less than 10 µM. Full article

(This article belongs to the Section Metabolites)

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11 pages, 2148 KiB

Open AccessArticle

NMR Study on the Inclusion Complexes of β-Cyclodextrin with Isoflavones

by Rui Zhao, Corine Sandström, Haiyang Zhang and Tianwei Tan

Molecules 2016, 21(4), 372; https://doi.org/10.3390/molecules21040372 - 28 Mar 2016

Cited by 55 | Viewed by 9195

Abstract

The structure of the inclusion complexes of β-cyclodextrin (β-CD) with daidzein and daidzin in D₂O were investigated using NMR spectroscopy. For the β-CD and daidzein system, two types of 1:1 complexes were formed with the daidzein deeply inserted into the CD [...] Read more.

The structure of the inclusion complexes of β-cyclodextrin (β-CD) with daidzein and daidzin in D₂O were investigated using NMR spectroscopy. For the β-CD and daidzein system, two types of 1:1 complexes were formed with the daidzein deeply inserted into the CD cavity with different orientations. For the β-CD/daidzin system, a 1:1 complex was formed with the flavonoid part of daidzin entering the CD cavity from the wide rim. The inclusion complexes determined by NMR were constructed using molecular docking. Furthermore, the mixture of puerarin, daidzein and daidzin, which are the major isoflavonoid components present in Radix puerariae, was analyzed by diffusion-ordered spectroscopy (DOSY) alone and upon addition of β-CD in order to mimic chromatographic conditions and compare their binding affinities. Full article

(This article belongs to the Collection Bioactive Compounds)

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16 pages, 992 KiB

Open AccessArticle

Synthesis of Novel Quaternary Ammonium Salts and Their in Vitro Antileishmanial Activity and U-937 Cell Cytotoxicity

by Sandra M. Duque-Benítez, Luz Amalia Ríos-Vásquez, Rogelio Ocampo-Cardona, David L. Cedeño, Marjorie A. Jones, Iván D. Vélez and Sara M. Robledo

Molecules 2016, 21(4), 381; https://doi.org/10.3390/molecules21040381 - 29 Mar 2016

Cited by 22 | Viewed by 6914

Abstract

This work describes the synthesis of a series of quaternary ammonium salts and the assessment of their in vitro antileishmanial activity and cytotoxicity. A preliminary discussion on a structure-activity relationship of the compounds is also included. Three series of quaternary ammonium salts were [...] Read more.

This work describes the synthesis of a series of quaternary ammonium salts and the assessment of their in vitro antileishmanial activity and cytotoxicity. A preliminary discussion on a structure-activity relationship of the compounds is also included. Three series of quaternary ammonium salts were prepared: (i) halomethylated quaternary ammonium salts (series I); (ii) non-halogenated quaternary ammonium salts (series II) and (iii) halomethylated choline analogs (series III). Assessments of their in vitro cytotoxicity in human promonocytic cells U-937 and antileishmanial activity in axenic amastigotes of L. (Viannia) panamensis (M/HOM/87/UA140-pIR-eGFP) were carried out using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide) micromethod. Antileishmanial activity was also tested in intracellular amastigotes of L. (V) panamensis using flow cytometry. High toxicity for human U937 cells was found with most of the compounds, which exhibited Lethal Concentration 50 (LC₅₀) values in the range of 9 to 46 μg/mL. Most of the compounds evidenced antileishmanial activity. In axenic amastigotes, the antileishmanial activity varied from 14 to 57 μg/mL, while in intracellular amastigotes their activity varied from 17 to 50 μg/mL. N-Chloromethyl-N,N-dimethyl-N-(4,4-diphenylbut-3-en-1-yl)ammonium iodide (1a), N-iodomethyl-N,N-dimethyl-N-(4,4-diphenylbut-3-en-1-yl)ammonium iodide (2a), N,N,N-trimethyl-N-(4,4-diphenylbut-3-en-1-yl)ammonium iodide (3a) and N,N,N-trimethyl-N-(5,5-diphenylpent-4-en-1-yl)ammonium iodide (3b) turned out to be the most active compounds against intracellular amastigotes of L. (V) panamensis, with EC₅₀ values varying between 24.7 for compound 3b and 38.4 μg/mL for compound 1a. Thus, these compounds represents new “hits” in the development of leishmanicidal drugs. Full article

(This article belongs to the Special Issue Recent Synthetic Aspects on the Chemistry of Nitro, Nitroso and Amino Compounds)

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19 pages, 5851 KiB

Open AccessArticle

Conformational and Molecular Structures of α,β-Unsaturated Acrylonitrile Derivatives: Photophysical Properties and Their Frontier Orbitals

by María Judith Percino, Margarita Cerón, Oscar Rodríguez, Guillermo Soriano-Moro, María Eugenia Castro, Víctor M. Chapela, Maxime A. Siegler and Enrique Pérez-Gutiérrez

Molecules 2016, 21(4), 389; https://doi.org/10.3390/molecules21040389 - 28 Mar 2016

Cited by 17 | Viewed by 7319

Abstract

We report single crystal X-ray diffraction (hereafter, SCXRD) analyses of derivatives featuring the electron-donor N-ethylcarbazole or the (4-diphenylamino)phenyl moieties associated with a -CN group attached to a double bond. The compounds are (2Z)-3-(4-(diphenylamino)-phenyl)-2-(pyridin-3-yl)prop-2-enenitrile (I), (2Z)-3-(4-(diphenylamino)phenyl)-2-(pyridin-4-yl)-prop-2-enenitrile ( [...] Read more.

We report single crystal X-ray diffraction (hereafter, SCXRD) analyses of derivatives featuring the electron-donor N-ethylcarbazole or the (4-diphenylamino)phenyl moieties associated with a -CN group attached to a double bond. The compounds are (2Z)-3-(4-(diphenylamino)-phenyl)-2-(pyridin-3-yl)prop-2-enenitrile (I), (2Z)-3-(4-(diphenylamino)phenyl)-2-(pyridin-4-yl)-prop-2-enenitrile (II) and (2Z)-3-(9-ethyl-9H-carbazol-3-yl)-2-(pyridin-2-yl)enenitrile (III). SCXRD analyses reveal that I and III crystallize in the monoclinic space groups P2/c with Z’ = 2 and C2/c with Z’ = 1, respectively. Compound II crystallized in the orthorhombic space group Pbcn with Z’ = 1. The molecular packing analysis was conducted to examine the pyridine core effect, depending on the ortho, meta- and para-positions of the nitrogen atom, with respect to the optical properties and number of independent molecules (Z’). It is found that the double bond bearing a diphenylamino moiety introduced properties to exhibit a strong π-π-interaction in the solid state. The compounds were examined to evaluate the effects of solvent polarity, the role of the molecular structure, and the molecular interactions on their self-assembly behaviors. Compound I crystallized with a cell with two conformers, anti and syn, due to interaction with solvent. DFT calculations indicated the anti and syn structures of I are energetically stable (less than 1 eV). Also electrochemical and photophysical properties of the compounds were investigated, as well as the determination of optimization calculations in gas and different solvent (chloroform, cyclohexane, methanol, ethanol, tetrahydrofuran, dichloromethane and dimethyl sulfoxide) in the Gaussian09 program. The effect of solvent by PCM method was also investigated. The frontier HOMO and LUMO energies and gap energies are reported. Full article

(This article belongs to the Special Issue Photoactive Molecules)

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12 pages, 1127 KiB

Open AccessArticle

Optimization of Betulinic Acid Extraction from Tecomella undulata Bark Using a Box-Behnken Design and Its Densitometric Validation

by Nahida Siddiqui and Vidhu Aeri

Molecules 2016, 21(4), 393; https://doi.org/10.3390/molecules21040393 - 6 Apr 2016

Cited by 11 | Viewed by 6552

Abstract

Betulinic acid (BA) is a pentacyclic triterpenoid acid obtained from the stem bark of Tecomella undulata Seem. (Bignoniaceae). Development of an efficient extraction method for the isolation of BA is important as it has a wide range of pharmacological activity. A Box-Behnken design [...] Read more.

Betulinic acid (BA) is a pentacyclic triterpenoid acid obtained from the stem bark of Tecomella undulata Seem. (Bignoniaceae). Development of an efficient extraction method for the isolation of BA is important as it has a wide range of pharmacological activity. A Box-Behnken design (BBD) was used to investigate the effect of extraction variables such as temperature (30–60 °C), time (4–8 h) and solvent to drug ratio (300–500 mL/100 g) on the maximization of BA yield and its quantification using validated densitometric high performance thin layer chromatography coupled with ultraviolet detection (HPTLC-VIS). A quadratic polynomial model was found to best fit the model with R² = 0.99. The optimized Soxhlet extraction yielded 2.449% w/w of BA at a temperature 53.86 °C, time 6.38 h and solvent to drug ratio 371 mL/100 g. BA in Tecomella undulata bark was detected at Rf value of 0.65 at 510 nm using the solvent system toluene–ethyl acetate–glacial acetic acid (8.5:1.5:0.02 v/v/v). The analytical method was validated and the linear regression analysis reflects good linear relationship (R² = 0.9902). Lower %RSD and SEM suggested that the developed HPTLC-VIS method was precise, accurate and robust. Therefore, these economical techniques are very efficient and promising for the extraction and quantification of pharmaceutically important BA. Full article

(This article belongs to the Collection Triterpenes and Triterpenoids)

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23 pages, 5374 KiB

Open AccessArticle

Polyphenolic Profile and Targeted Bioactivity of Methanolic Extracts from Mediterranean Ethnomedicinal Plants on Human Cancer Cell Lines

by Antonino Pollio, Armando Zarrelli, Valeria Romanucci, Alfredo Di Mauro, Federica Barra, Gabriele Pinto, Elvira Crescenzi, Emanuela Roscetto and Giuseppe Palumbo

Molecules 2016, 21(4), 395; https://doi.org/10.3390/molecules21040395 - 23 Mar 2016

Cited by 37 | Viewed by 7764

Abstract

The methanol extracts of the aerial part of four ethnomedicinal plants of Mediterranean region, two non-seed vascular plants, Equisetum hyemale L. and Phyllitis scolopendrium (L.) Newman, and two Spermatophyta, Juniperus communis L. (J. communis) and Cotinus coggygria Scop. (C. coggygria [...] Read more.

The methanol extracts of the aerial part of four ethnomedicinal plants of Mediterranean region, two non-seed vascular plants, Equisetum hyemale L. and Phyllitis scolopendrium (L.) Newman, and two Spermatophyta, Juniperus communis L. (J. communis) and Cotinus coggygria Scop. (C. coggygria), were screened against four human cells lines (A549, MCF7, TK6 and U937). Only the extracts of J. communis and C. coggygria showed marked cytotoxic effects, affecting both cell morphology and growth. A dose-dependent effect of these two extracts was also observed on the cell cycle distribution. Incubation of all the cell lines in a medium containing J. communis extract determined a remarkable accumulation of cells in the G2/M phase, whereas the C. coggygria extract induced a significant increase in the percentage of G1 cells. The novelty of our findings stands on the observation that the two extracts, consistently, elicited coherent effects on the cell cycle in four cell lines, independently from their phenotype, as two of them have epithelial origin and grow adherent and two are lymphoblastoid and grow in suspension. Even the expression profiles of several proteins regulating cell cycle progression and cell death were affected by both extracts. LC-MS investigation of methanol extract of C. coggygria led to the identification of twelve flavonoids (compounds 1–11, 19) and eight polyphenols derivatives (12–18, 20), while in J. communis extract, eight flavonoids (21–28), a α-ionone glycoside (29) and a lignin (30) were found. Although many of these compounds have interesting individual biological activities, their natural blends seem to exert specific effects on the proliferation of cell lines either growing adherent or in suspension, suggesting potential use in fighting cancer. Full article

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

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10 pages, 1284 KiB

Open AccessArticle

Structure-Based Drug Design of Small Molecule Peptide Deformylase Inhibitors to Treat Cancer

by Jian Gao, Tao Wang, Shengzhi Qiu, Yasheng Zhu, Li Liang and Youguang Zheng

Molecules 2016, 21(4), 396; https://doi.org/10.3390/molecules21040396 - 23 Mar 2016

Cited by 11 | Viewed by 8024

Abstract

Human peptide deformylase (HsPDF) is an important target for anticancer drug discovery. In view of the limited HsPDF, inhibitors were reported, and high-throughput virtual screening (HTVS) studies based on HsPDF for developing new PDF inhibitors remain to be reported. We reported here on [...] Read more.

Human peptide deformylase (HsPDF) is an important target for anticancer drug discovery. In view of the limited HsPDF, inhibitors were reported, and high-throughput virtual screening (HTVS) studies based on HsPDF for developing new PDF inhibitors remain to be reported. We reported here on diverse small molecule inhibitors with excellent anticancer activities designed based on HTVS and molecular docking studies using the crystal structure of HsPDF. The compound M7594_0037 exhibited potent anticancer activities against HeLa, A549 and MCF-7 cell lines with IC_50s of 35.26, 29.63 and 24.63 μM, respectively. Molecular docking studies suggested that M7594_0037 and its three derivatives could interact with HsPDF by several conserved hydrogen bonds. Moreover, the pharmacokinetic and toxicity properties of M7594_0037 and its derivatives were predicted using the OSIRIS property explorer. Thus, M7594_0037 and its derivatives might represent a promising scaffold for the further development of novel anticancer drugs. Full article

(This article belongs to the Section Medicinal Chemistry)

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13 pages, 2813 KiB

Open AccessArticle

Extraction Optimization, Purification and Physicochemical Properties of Polysaccharides from Gynura medica

by Fengwei Li, Jian Gao, Feng Xue, Xiaohong Yu and Tao Shao

Molecules 2016, 21(4), 397; https://doi.org/10.3390/molecules21040397 - 23 Mar 2016

Cited by 24 | Viewed by 6287

Abstract

Extraction of polysaccharides from Gynura medica (GMPs) was optimized by response surface methodology (RSM). A central composition design including three parameters, namely extraction temperature (X₁), ratio of water to raw material (X₂) and extraction time (X₃), was [...] Read more.

Extraction of polysaccharides from Gynura medica (GMPs) was optimized by response surface methodology (RSM). A central composition design including three parameters, namely extraction temperature (X₁), ratio of water to raw material (X₂) and extraction time (X₃), was used. The best conditions were extraction temperature of 91.7 °C, extraction time of 4.06 h and ratio of water to raw material of 29.1 mL/g. Under the optimized conditions, the yield of GMPs was 5.56%, which was similar to the predicted polysaccharides yield of 5.66%. A fraction named GMP-1 was obtained after isolation and purification by DEAE-52 and Sephadex G-100 gel chromatography, respectively. GMP-1, with a molecular weight of 401 kDa, mainly consisted of galacturonic acid (GalA), xylose (Xyl), glucose (Glu). Infrared spectroscopy was used to characterize the major functional groups of GMP-1 and the results indicated that it was an acidic polysaccharide. The antioxidant and α-glucosidase inhibitory activities of GMPs and GMP-1 were determined in vitro. The results indicated that GMPs and GMP-1 show potential for use in functional foods or medicines. Full article

(This article belongs to the Section Natural Products Chemistry)

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14 pages, 2158 KiB

Open AccessArticle

The Tissue Distribution and Urinary Excretion Study of Gallic Acid and Protocatechuic Acid after Oral Administration of Polygonum Capitatum Extract in Rats

by Feng-Wei Ma, Qing-Fang Deng, Xin Zhou, Xiao-Jian Gong, Yang Zhao, Hua-Guo Chen and Chao Zhao

Molecules 2016, 21(4), 399; https://doi.org/10.3390/molecules21040399 - 24 Mar 2016

Cited by 26 | Viewed by 6813

Abstract

In the present study, we investigated the tissue distribution and urinary excretion of gallic acid (GA) and protocatechuic acid (PCA) after rat oral administration of aqueous extract of Polygonum capitatum (P. capitatum, named Herba Polygoni Capitati in China). An UHPLC-MS/MS analytical [...] Read more.

In the present study, we investigated the tissue distribution and urinary excretion of gallic acid (GA) and protocatechuic acid (PCA) after rat oral administration of aqueous extract of Polygonum capitatum (P. capitatum, named Herba Polygoni Capitati in China). An UHPLC-MS/MS analytical method was developed and adopted for quantification of GA and PCA in different tissue homogenate and urine samples. Interestingly, we found that GA and PCA showed a relatively targeted distribution in kidney tissue after dosing 60 mg/kg P. capitatum extract (equivalent to 12 mg/kg of GA and 0.9 mg/kg of PCA). The concentrations of GA and PCA in the kidney tissue reached 1218.62 ng/g and 43.98 ng/g, respectively, at one hour after oral administration. The results helped explain the empirical use of P. capitatum for kidney diseases in folk medicine. Further studies on urinary excretion of P. capitatum extract indicated that GA and PCA followed a concentrated elimination over a 4-h period. The predominant metabolites were putatively identified to be 4-methylgallic acid (4-OMeGA) and 4-methylprotocatechuic acid (4-OMePCA) by analyzing their precursor ions and characteristic fragment ions using tandem mass spectrometry. However, the amount of unchanged GA and PCA that survived the metabolism were about 14.60% and 15.72% of the total intake, respectively, which is reported for the first time in this study. Full article

(This article belongs to the Special Issue New Frontiers on the Metabolism, Bioavailability and Health Effects of Phenolic Compounds)

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16 pages, 1053 KiB

Open AccessArticle

Imidazopyranotacrines as Non-Hepatotoxic, Selective Acetylcholinesterase Inhibitors, and Antioxidant Agents for Alzheimer's Disease Therapy

by Houssem Boulebd, Lhassane Ismaili, Manuela Bartolini, Abdelmalek Bouraiou, Vincenza Andrisano, Helene Martin, Alexandre Bonet, Ignacio Moraleda, Isabel Iriepa, Mourad Chioua, Ali Belfaitah and José Marco-Contelles

Molecules 2016, 21(4), 400; https://doi.org/10.3390/molecules21040400 - 24 Mar 2016

Cited by 25 | Viewed by 8727

Abstract

Herein we describe the synthesis and in vitro biological evaluation of thirteen new, racemic, diversely functionalized imidazo pyranotacrines as non-hepatotoxic, multipotent tacrine analogues. Among these compounds, 1-(5-amino-2-methyl-4-(1-methyl-1H-imidazol-2-yl)-6,7,8,9-tetrahydro-4H-pyrano[2,3-b]quinolin-3-yl)ethan-1-one (4) is non-hepatotoxic (cell viability assay on HepG2 cells), a [...] Read more.

Herein we describe the synthesis and in vitro biological evaluation of thirteen new, racemic, diversely functionalized imidazo pyranotacrines as non-hepatotoxic, multipotent tacrine analogues. Among these compounds, 1-(5-amino-2-methyl-4-(1-methyl-1H-imidazol-2-yl)-6,7,8,9-tetrahydro-4H-pyrano[2,3-b]quinolin-3-yl)ethan-1-one (4) is non-hepatotoxic (cell viability assay on HepG2 cells), a selective but moderately potent EeAChE inhibitor (IC₅₀ = 38.7 ± 1.7 μM), and a very potent antioxidant agent on the basis of the ORAC test (2.31 ± 0.29 μmol·Trolox/μmol compound). Full article

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

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17 pages, 7787 KiB

Open AccessArticle

From Nanorods to Nanowires of CdS Synthesized by a Solvothermal Method: Influence of the Morphology on the Photoactivity for Hydrogen Evolution from Water

by Fernando Vaquero, José Luis G. Fierro and Rufino M. Navarro Yerga

Molecules 2016, 21(4), 401; https://doi.org/10.3390/molecules21040401 - 24 Mar 2016

Cited by 26 | Viewed by 7212

Abstract

The effect of temperature and water/thiourea ratio on the growth, crystallinity and morphological characteristics of CdS nanostructures synthetized by a solvothermal method using ethylenediamine as solvent were studied. The temperature and water/thiourea ratio used in the synthesis determine the surface area, shape, length [...] Read more.

The effect of temperature and water/thiourea ratio on the growth, crystallinity and morphological characteristics of CdS nanostructures synthetized by a solvothermal method using ethylenediamine as solvent were studied. The temperature and water/thiourea ratio used in the synthesis determine the surface area, shape, length and degree of crystallinity of the CdS nanostructures obtained. Nanowires of high crystallinity and length were obtained when the solvothermal synthesis was performed at 190 °C, while nanorods with lower length and crystallinity were obtained as the solvothermal temperature decreased to 120 °C. The change in the water/thiourea ratio affects the crystallinity and length of the CdS nanostructures to a lesser extent than temperature. Nevertheless an increase in the water/thiourea ratio used during the solvothermal synthesis resulted in CdS nanorods with higher crystallinity, lower aspect ratio and lower specific surface area. Textural, structural and surface properties of the prepared CdS nanostructures were determined and related to the activity results in the production of hydrogen from aqueous solutions containing SO₃²⁻ + S²⁻ under visible light. Full article

(This article belongs to the Special Issue Photocatalytic Water Splitting—the Untamed Dream)

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11 pages, 1872 KiB

Open AccessArticle

A Series of Oleanolic Acid Derivatives as Anti-Hepatitis B Virus Agents: Design, Synthesis, and in Vitro and in Vivo Biological Evaluation

by Wenqiang Yan, Chenze Zhang, Bi Li, Xin Xu, Miao Liang, Shun Gu, Fuhao Chu, Bing Xu, Jian Ren, Penglong Wang and Haimin Lei

Molecules 2016, 21(4), 402; https://doi.org/10.3390/molecules21040402 - 24 Mar 2016

Cited by 24 | Viewed by 6375

Abstract

A series of oleanolic acid derivatives were synthesized by diverse reactions, including the introduction of conjugated alkadiene and epoxy ring moieties formed by means of photosensitized oxidation. Eosin Y was used as photosensitizer during this process. Next the cytotoxicity of the products was [...] Read more.

A series of oleanolic acid derivatives were synthesized by diverse reactions, including the introduction of conjugated alkadiene and epoxy ring moieties formed by means of photosensitized oxidation. Eosin Y was used as photosensitizer during this process. Next the cytotoxicity of the products was evaluated on HepG2.2.15 cells to determine the appropriate treatment concentration for the subsequent experiments. Most of the OA derivatives exhibited anti-HBV antigens secretion activity in HepG2.2.15 cells. Among the tested compounds, OA-4 (3.13 µg/mL) showed significant activity against the secretion of HBsAg, HBeAg, and HBV DNA replication with inhibitory ratios of 90.52% ± 1.78%, 31.55% ± 3.65%, and 94.57% ± 3.11% after 6 days, respectively. Besides, OA-4 was further investigated in a duck model with DHBV infection. When OA-4 was administered at a dosage of 500 mg/kg, the results revealed a significant inhibitory effects of DHBV at 19.94% ± 2.87%, 28.80% ± 3.62% and 29.25% ± 2.65% at days 5, 10, and 3 after the cessation of OA-4 treatment, respectively. It’s worth noting that OA-4 is superior to lamivudine in the inhibition of rebound of viral replication rate. The structure–activity relationships of OA derivatives had been preliminary discussed, which should be useful to explore further novel anti-HBV agents. Full article

(This article belongs to the Section Medicinal Chemistry)

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10 pages, 1050 KiB

Open AccessArticle

Effect of Drying Methods on the Steroidal Alkaloid Content of Potato Peels, Shoots and Berries

by Mohammad B. Hossain, Nigel P. Brunton and Dilip K. Rai

Molecules 2016, 21(4), 403; https://doi.org/10.3390/molecules21040403 - 25 Mar 2016

Cited by 24 | Viewed by 7493

Abstract

The present study has found that dried potato samples yielded significantly higher levels of steroidal alkaloids such as α-solanine and α-chaconine than the corresponding fresh samples, as determined by the UPLC-MS/MS technique. Among the drying techniques used, air drying had the highest effect [...] Read more.

The present study has found that dried potato samples yielded significantly higher levels of steroidal alkaloids such as α-solanine and α-chaconine than the corresponding fresh samples, as determined by the UPLC-MS/MS technique. Among the drying techniques used, air drying had the highest effect on steroidal alkaloid contents, followed by freeze drying and vacuum oven drying. There was no significant difference between the freeze dried and vacuum oven dried samples in their α-chaconine contents. However, freeze dried potato shoots and berries had significantly higher α-solanine contents (825 µg/g dry weight (DW) in shoots and 2453 µg/g DW in berries) than the vacuum oven dried ones (325 µg/g dry weight (DW) in shoots and 2080 µg/g DW in berries). The kinetics of steroidal alkaloid contents of potato shoots during air drying were monitored over a period of 21 days. Both α-solanine and α-chaconine content increased to their maximum values, 875 µg/g DW and 3385 µg/g DW, respectively, after 7 days of drying. The steroidal alkaloid contents of the shoots decreased significantly at day 9, and then remained unchanged until day 21. In line with the potato shoots, air dried potato tuber peels also had higher steroidal alkaloid content than the freeze dried and vacuum oven dried samples. However, a significant decrease of steroidal alkaloid content was observed in air dried potato berries, possibly due to degradation during slicing of the whole berries prior to air drying. Remarkable variation in steroidal alkaloid contents among different tissue types of potato plants was observed with the potato flowers having the highest content. Full article

(This article belongs to the Section Natural Products Chemistry)

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18 pages, 4446 KiB

Open AccessArticle

The Chemical Composition of Achillea wilhelmsii C. Koch and Its Desirable Effects on Hyperglycemia, Inflammatory Mediators and Hypercholesterolemia as Risk Factors for Cardiometabolic Disease

by Elian Khazneh, Petra Hřibová, Jan Hošek, Pavel Suchý, Peter Kollár, Gabriela Pražanová, Jan Muselík, Zuzana Hanaková, Jiří Václavík, Michał Miłek, Jaroslav Legáth and Karel Šmejkal

Molecules 2016, 21(4), 404; https://doi.org/10.3390/molecules21040404 - 25 Mar 2016

Cited by 29 | Viewed by 8916

Abstract

This study was done to identify the content compounds of Achillea wilhelmsii (A. wilhelmsii) and to evaluate its hypoglycemic and anti-hypercholesterolemic activity and effect on inflammatory mediators. The extracts and fractions of A. wilhelmsii were thoroughly analyzed using high performance liquid [...] Read more.

This study was done to identify the content compounds of Achillea wilhelmsii (A. wilhelmsii) and to evaluate its hypoglycemic and anti-hypercholesterolemic activity and effect on inflammatory mediators. The extracts and fractions of A. wilhelmsii were thoroughly analyzed using high performance liquid chromatography (HPLC), and the total content of phenols and flavonoids was determined. The hypoglycemic activity was evaluated in vivo using alloxan-induced diabetic mice. The effect upon inflammatory mediators was evaluated in vitro using the human monocytic leukemia cell line (THP-1). The anti-hypercholesterolemic activity was evaluated in vitro using the 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase assay kit. The water extract (WE)-treated group showed the highest reduction in the fasting blood glucose levels (FBGL). The chloroform fraction (CF) and ethyl acetate fraction (EAF) both showed a significant ability to reduce the secretion of tumor necrosis factor alpha (TNF-α). The EAF, however, also attenuated the levels of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9). The CF showed the most significant 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) inhibition activity. The five main compounds in the CF were isolated and identified. Out of the five compounds in the CF, 1β,10β-epoxydesacetoxymatricarin (CP1) and leucodin (CP2) showed the highest anti-hypercholesterolemic potential. A molecular docking study provided corresponding results. Full article

(This article belongs to the Special Issue Effects of Natural Products in the Context of Cardiometabolic Disease)

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11 pages, 1500 KiB

Open AccessArticle

Insolubilization of Chestnut Shell Pigment for Cu(II) Adsorption from Water

by Zeng-Yu Yao, Jian-Hua Qi, Yong Hu and Ying Wang

Molecules 2016, 21(4), 405; https://doi.org/10.3390/molecules21040405 - 28 Mar 2016

Cited by 17 | Viewed by 4889

Abstract

Chestnut shell pigment (CSP) is melanin from an agricultural waste. It has potential as an adsorbent for wastewater treatment but cannot be used in its original state because of its solubility in water. We developed a new method to convert CSP to insolubilized [...] Read more.

Chestnut shell pigment (CSP) is melanin from an agricultural waste. It has potential as an adsorbent for wastewater treatment but cannot be used in its original state because of its solubility in water. We developed a new method to convert CSP to insolubilized chestnut shell pigment (ICSP) by heating, and the Cu(II) adsorption performance of ICSP was evaluated. The conversion was characterized, and the thermal treatment caused dehydration and loss of carboxyl groups and aliphatic structures in CSP. The kinetic adsorption behavior obeyed the pseudo-second-order rate law, and the equilibrium adsorption data were well described with both the Langmuir and the Freundlich isotherms. ICSP can be used as a renewable, readily-available, easily-producible, environmentally-friendly, inexpensive and effective adsorbent to remove heavy-metal from aquatic environments. Full article

(This article belongs to the Section Green Chemistry)

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16 pages, 832 KiB

Open AccessArticle

Protective Effect of a (Poly)phenol-Rich Extract Derived from Sweet Cherries Culls against Oxidative Cell Damage

by Ana A. Matias, Rita Rosado-Ramos, Sara L. Nunes, Inês Figueira, Ana Teresa Serra, Maria R. Bronze, Claúdia N. Santos and Catarina M. M. Duarte

Molecules 2016, 21(4), 406; https://doi.org/10.3390/molecules21040406 - 24 Mar 2016

Cited by 39 | Viewed by 6910

Abstract

Oxidative stress is one of the key phenomena behind the most common types of chronic diseases. Therefore, the modulation of oxidative stress is an interesting target for acting either through prevention or as a therapeutic approach. In this work, a Portuguese variety of [...] Read more.

Oxidative stress is one of the key phenomena behind the most common types of chronic diseases. Therefore, the modulation of oxidative stress is an interesting target for acting either through prevention or as a therapeutic approach. In this work, a Portuguese variety of cherry (Saco Cherry) was processed in order to obtain a potent in vitro antioxidant phenolic-rich extract (Ch-PRE), which was further explored to evaluate its potential application as nutraceutical agent against cellular oxidative stress damage. Ch-PRE was mainly composed of anthocyanins, particularly cyanidin-3-rutinoside, cyanidin-3-glucoside, peonidin-3-glucoside and neochlorogenic acid, and exhibited a potent chemical antioxidant activity expressed by its oxygen radical absorbance capacity (ORAC) and hydroxyl radical averting capacity (HORAC) values. Ch-PRE also displayed effective intracellular radical scavenging properties in intestinal epithelial and neuronal cells challenged with oxidative stress but showed a different order of effectiveness regarding the modulation of endogenous antioxidant system. Ch-PRE could be an attractive candidate to formulate an agent for the prevention of oxidative stress-induced disorders such as intestinal inflammation disorders or with an appropriated delivery system for neurodegenerative diseases. Full article

(This article belongs to the Special Issue Dietary Bioactive Compounds: Metabolism, Mechanisms and Translational Significance for Health and Prevention of Diseases)

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8 pages, 1232 KiB

Open AccessArticle

Synthesis of Ethano-Bridged Diazapolycenes as Potential Precursors for Diazapolycenes and Their Properties

by Moinul Karim and Yurngdong Jahng

Molecules 2016, 21(4), 407; https://doi.org/10.3390/molecules21040407 - 25 Mar 2016

Cited by 2 | Viewed by 4867

Abstract

A series of ethanodiazapolycenes were prepared in 87%–89% yields by Friedländer reactions of three o-aminoarenecarbaldehydes with bicyclo[2.2.2]octane-2,5-dione and their spectral, thermal, and structural properties were studied. Subsequent attempts to convert them to diazapolycenes have proved unsuccessful. Full article

(This article belongs to the Special Issue New Molecular Materials)

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18 pages, 2425 KiB

Open AccessArticle

Simultaneous Quantitation of Free Amino Acids, Nucleosides and Nucleobases in Sipunculus nudus by Ultra-High Performance Liquid Chromatography with Triple Quadrupole Mass Spectrometry

by Yahui Ge, Yuping Tang, Sheng Guo, Xin Liu, Zhenhua Zhu, Lili Zhang, Pei Liu, Shaoxiong Ding, Xiangzhi Lin, Rurong Lin and Jin-ao Duan

Molecules 2016, 21(4), 408; https://doi.org/10.3390/molecules21040408 - 25 Mar 2016

Cited by 18 | Viewed by 6397

Abstract

To evaluate the nutritional and functional value of Sipunculus nudus, a rapid, simple and sensitive analytical method was developed using ultra-high performance liquid chromatography coupled with a triple quadrupole mass detection in multiple-reaction monitoring mode for the simultaneous quantitative determination of 25 [...] Read more.

To evaluate the nutritional and functional value of Sipunculus nudus, a rapid, simple and sensitive analytical method was developed using ultra-high performance liquid chromatography coupled with a triple quadrupole mass detection in multiple-reaction monitoring mode for the simultaneous quantitative determination of 25 free amino acids and 16 nucleosides and nucleobases in S. nudus within 20 min, which was confirmed to be reproducible and accurate. The limits of detection (LODs) and quantification (LOQs) were between 0.003–0.229 μg/mL and 0.008–0.763 μg/mL for the 41 analytes, respectively. The established method was applied to analyze 19 batches of S. nudus samples from four habitats with two different processing methods. The results showed that S. nudus contained a variety of free amino acids, nucleosides and nucleobases in sufficient quantity and reasonable proportion. They also demonstrated that the contents of these compounds in different parts of S. nudus were significantly discriminating, which were in the order: (highest) coelomic fluid > body wall > intestine (lowest). The method is simple and accurate, and could serve as a technical support for establishing quality control of S. nudus and other functional seafoods. Moreover, the research results also laid foundation for further exploitation and development of S. nudus. Full article

(This article belongs to the Section Natural Products Chemistry)

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8 pages, 492 KiB

Open AccessArticle

In-Vitro Anticancer Evaluation of Some Novel Thioureido-Benzensulfonamide Derivatives

by Mostafa M. Ghorab, Mansour S. Alsaid, Mohammed S. Al-Dosari, Marwa G. El-Gazzar and Ahmed H. Arbab

Molecules 2016, 21(4), 409; https://doi.org/10.3390/molecules21040409 - 25 Mar 2016

Cited by 11 | Viewed by 5613

Abstract

A novel series of sulfonamide derivatives (14 compounds) bearing thiourea moieties were efficiently synthesized and evaluated for their possible in vitro anticancer activity against four human tumor cell lines. The results indicated that compound 6 was the most potent, showing effectiveness on all [...] Read more.

A novel series of sulfonamide derivatives (14 compounds) bearing thiourea moieties were efficiently synthesized and evaluated for their possible in vitro anticancer activity against four human tumor cell lines. The results indicated that compound 6 was the most potent, showing effectiveness on all the tested cell lines. Compounds 7 and 10 also showed promising results. 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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24 pages, 3807 KiB

Open AccessArticle

Synthesis, Molecular Modelling and Biological Evaluation of Novel Heterodimeric, Multiple Ligands Targeting Cholinesterases and Amyloid Beta

by Michalina Hebda, Marek Bajda, Anna Więckowska, Natalia Szałaj, Anna Pasieka, Dawid Panek, Justyna Godyń, Tomasz Wichur, Damijan Knez, Stanislav Gobec and Barbara Malawska

Molecules 2016, 21(4), 410; https://doi.org/10.3390/molecules21040410 - 26 Mar 2016

Cited by 32 | Viewed by 8807

Abstract

Cholinesterases and amyloid beta are one of the major biological targets in the search for a new and efficacious treatment of Alzheimer’s disease. The study describes synthesis and pharmacological evaluation of new compounds designed as dual binding site acetylcholinesterase inhibitors. Among the synthesized [...] Read more.

Cholinesterases and amyloid beta are one of the major biological targets in the search for a new and efficacious treatment of Alzheimer’s disease. The study describes synthesis and pharmacological evaluation of new compounds designed as dual binding site acetylcholinesterase inhibitors. Among the synthesized compounds, two deserve special attention—compounds 42 and 13. The former is a saccharin derivative and the most potent and selective acetylcholinesterase inhibitor (EeAChE IC₅₀ = 70 nM). Isoindoline-1,3-dione derivative 13 displays balanced inhibitory potency against acetyl- and butyrylcholinesterase (BuChE) (EeAChE IC₅₀ = 0.76 μM, EqBuChE IC₅₀ = 0.618 μM), and it inhibits amyloid beta aggregation (35.8% at 10 μM). Kinetic studies show that the developed compounds act as mixed or non-competitive acetylcholinesterase inhibitors. According to molecular modelling studies, they are able to interact with both catalytic and peripheral active sites of the acetylcholinesterase. Their ability to cross the blood-brain barrier (BBB) was confirmed in vitro in the parallel artificial membrane permeability BBB assay. These compounds can be used as a solid starting point for further development of novel multifunctional ligands as potential anti-Alzheimer’s agents. Full article

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

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12 pages, 2188 KiB

Open AccessArticle

Robust Synthesis of Ciprofloxacin-Capped Metallic Nanoparticles and Their Urease Inhibitory Assay

by Muhammad Nisar, Shujaat Ali Khan, Mughal Qayum, Ajmal Khan, Umar Farooq, Hawa Z.E. Jaafar, Muhammad Zia-Ul-Haq and Rashid Ali

Molecules 2016, 21(4), 411; https://doi.org/10.3390/molecules21040411 - 25 Mar 2016

Cited by 24 | Viewed by 8039

Abstract

The fluoroquinolone antibacterial drug ciprofloxacin (cip) has been used to cap metallic (silver and gold) nanoparticles by a robust one pot synthetic method under optimized conditions, using NaBH₄ as a mild reducing agent. Metallic nanoparticles (MNPs) showed constancy against variations in pH, [...] Read more.

The fluoroquinolone antibacterial drug ciprofloxacin (cip) has been used to cap metallic (silver and gold) nanoparticles by a robust one pot synthetic method under optimized conditions, using NaBH₄ as a mild reducing agent. Metallic nanoparticles (MNPs) showed constancy against variations in pH, table salt (NaCl) solution, and heat. Capping with metal ions (Ag/Au-cip) has significant implications for the solubility, pharmacokinetics and bioavailability of fluoroquinolone molecules. The metallic nanoparticles were characterized by several techniques such as ultraviolet visible spectroscopy (UV), atomic force microscopy (AFM), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and energy dispersive X-ray (EDX) methods. The nanoparticles synthesized using silver and gold were subjected to energy dispersive X-ray tests in order to show their metallic composition. The NH moiety of the piperazine group capped the Ag/Au surfaces, as revealed by spectroscopic studies. The synthesized nanoparticles were also assessed for urease inhibition potential. Fascinatingly, both Ag-cip and Au-cip NPs exhibited significant urease enzyme inhibitory potential, with IC₅₀ = 1.181 ± 0.02 µg/mL and 52.55 ± 2.3 µg/mL, compared to ciprofloxacin (IC₅₀ = 82.95 ± 1.62 µg/mL). MNPs also exhibited significant antibacterial activity against selected bacterial strains. Full article

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

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9 pages, 2426 KiB

Open AccessArticle

Mechanistic Insight of Bivalent Compound 21MO as Potential Neuroprotectant for Alzheimer’s Disease

by John M. Saathoff, Kai Liu, Jeremy E. Chojnacki, Liu He, Qun Chen, Edward J. Lesnefsky and Shijun Zhang

Molecules 2016, 21(4), 412; https://doi.org/10.3390/molecules21040412 - 25 Mar 2016

Cited by 9 | Viewed by 5525

Abstract

We have recently developed a bivalent strategy to provide novel compounds that potentially target multiple risk factors involved in the development of Alzheimer’s disease (AD). Our previous studies employing a bivalent compound with a shorter spacer (17MN) implicated that this compound [...] Read more.

We have recently developed a bivalent strategy to provide novel compounds that potentially target multiple risk factors involved in the development of Alzheimer’s disease (AD). Our previous studies employing a bivalent compound with a shorter spacer (17MN) implicated that this compound can localize into mitochondria and endoplasmic reticulum (ER), thus interfering with the change of mitochondria membrane potential (MMP) and Ca²⁺ levels in MC65 cells upon removal of tetracycline (TC). In this report, we examined the effects by a bivalent compound with a longer spacer (21MO) in MC65 cells. Our results demonstrated that 21MO suppressed the change of MMP, possibly via interaction with the mitochondrial complex I in MC65 cells. Interestingly, 21MO did not show any effects on the Ca²⁺ level upon TC removal in MC65 cells. Our previous studies suggested that the mobilization of Ca²⁺ in MC65 cells, upon withdraw of TC, originated from ER, so the results implicated that 21MO may preferentially interact with mitochondria in MC65 cells under the current experimental conditions. Collectively, the results suggest that bivalent compounds with varied spacer length and cell membrane anchor moiety may exhibit neuroprotective activities via different mechanisms of action. Full article

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

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9 pages, 1998 KiB

Open AccessArticle

Microwave-Assisted γ-Valerolactone Production for Biomass Lignin Extraction: A Cascade Protocol

by Silvia Tabasso, Giorgio Grillo, Diego Carnaroglio, Emanuela Calcio Gaudino and Giancarlo Cravotto

Molecules 2016, 21(4), 413; https://doi.org/10.3390/molecules21040413 - 26 Mar 2016

Cited by 33 | Viewed by 8583

Abstract

The general need to slow the depletion of fossil resources and reduce carbon footprints has led to tremendous effort being invested in creating “greener” industrial processes and developing alternative means to produce fuels and synthesize platform chemicals. This work aims to design a [...] Read more.

The general need to slow the depletion of fossil resources and reduce carbon footprints has led to tremendous effort being invested in creating “greener” industrial processes and developing alternative means to produce fuels and synthesize platform chemicals. This work aims to design a microwave-assisted cascade process for a full biomass valorisation cycle. GVL (γ-valerolactone), a renewable green solvent, has been used in aqueous acidic solution to achieve complete biomass lignin extraction. After lignin precipitation, the levulinic acid (LA)-rich organic fraction was hydrogenated, which regenerated the starting solvent for further biomass delignification. This process does not requires a purification step because GVL plays the dual role of solvent and product, while the reagent (LA) is a product of biomass delignification. In summary, this bio-refinery approach to lignin extraction is a cascade protocol in which the solvent loss is integrated into the conversion cycle, leading to simplified methods for biomass valorisation. Full article

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

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17 pages, 2700 KiB

Open AccessArticle

Effect of Genotype and Environment on Salvia miltiorrhiza Roots Using LC/MS-Based Metabolomics

by Qi Zhao, Zhenqiao Song, Xinsheng Fang, Yuling Pan, Linlin Guo, Tian Liu and Jianhua Wang

Molecules 2016, 21(4), 414; https://doi.org/10.3390/molecules21040414 - 26 Mar 2016

Cited by 44 | Viewed by 8471

Abstract

Salvia miltiorrhiza (S. miltiorrhiza) Bunge is broadly used as herbal medicine for the clinical treatments of cardiovascular and cerebrovascular diseases. Despite its commercial and medicinal values, few systematic studies on the metabolome of S. miltiorrhiza roots have been carried out so [...] Read more.

Salvia miltiorrhiza (S. miltiorrhiza) Bunge is broadly used as herbal medicine for the clinical treatments of cardiovascular and cerebrovascular diseases. Despite its commercial and medicinal values, few systematic studies on the metabolome of S. miltiorrhiza roots have been carried out so far. We systematically described the metabolic profiles of S. miltiorrhiza using high pressure liquid chromatography mass spectrometry (LC/MS) in conjunction with multivariate statistical analyses, aimed at monitoring their biological variations of secondary metabolites related to three locations and four S. miltiorrhiza genotypes. A total of 40 bioactive constituents were putatively annotated in S. miltiorrhiza root samples. This study found that both the same S. miltiorrhiza genotype growing at three different locations and four S. miltiorrhiza genotypes growing at the same location had significant metabonomic differences identified by the principal component analysis (PCA) approach. By using orthogonal projection to latent structure with discriminant analysis (OPLS-DA), 16 and 14 secondary metabolites can be used as potential location-specific and genotype-specific markers in S. miltiorrhiza, respectively. The specificity of LC/MS profiles offered a powerful tool to discriminate S. miltiorrhiza samples according to genotypes or locations. Full article

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

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16 pages, 2626 KiB

Open AccessArticle

Purification and Characterization of a White Laccase with Pronounced Dye Decolorizing Ability and HIV-1 Reverse Transcriptase Inhibitory Activity from Lepista nuda

by Mengjuan Zhu, Guoqing Zhang, Li Meng, Hexiang Wang, Kexiang Gao and Tb Ng

Molecules 2016, 21(4), 415; https://doi.org/10.3390/molecules21040415 - 26 Mar 2016

Cited by 31 | Viewed by 7048

Abstract

A strain LN07 with high laccase yield was identified as basidiomycete fungus Lepista nuda from which a white laccase without type I copper was purified and characterized. The laccase was a monomeric protein with a molecular mass of 56 kDa. Its N-terminal amino [...] Read more.

A strain LN07 with high laccase yield was identified as basidiomycete fungus Lepista nuda from which a white laccase without type I copper was purified and characterized. The laccase was a monomeric protein with a molecular mass of 56 kDa. Its N-terminal amino acid sequence was AIGPAADLHIVNKDISPDGF. Besides, eight inner peptide sequences were determined and lac4, lac5 and lac6 sequences were in the Cu²⁺ combination and conservation zones of laccases. HIV-1 reverse transcriptase was inhibited by the laccase with a half-inhibitory concentration of 0.65 μM. Cu²⁺ ions (1.5 mM) enhanced the laccase production and the optimal pH and temperature of the laccase were pH 3.0 and 50 °C, respectively. The Km and Vmax of the laccase using ABTS as substrate were respectively 0.19 mM and 195 μM. Several dyes including laboratory dyes and textile dyes used in this study, such as Methyl red, Coomassie brilliant blue, Reactive brilliant blue and so on, were decolorized in different degrees by the purified laccase. By LC-MS analysis, Methyl red was structurally degraded by the laccase. Moreover, the laccase affected the absorbance at the maximum wavelength of many pesticides. Thus, the white laccase had potential commercial value for textile finishing and wastewater treatment. Full article

(This article belongs to the Section Natural Products Chemistry)

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10 pages, 5043 KiB

Open AccessArticle

In Silico Discovery of Potential Uridine-Cytidine Kinase 2 Inhibitors from the Rhizome of Alpinia mutica

by Ibrahim Malami, Ahmad Bustamam Abdul, Rasedee Abdullah, Nur Kartinee Bt Kassim, Peter Waziri and Imaobong Christopher Etti

Molecules 2016, 21(4), 417; https://doi.org/10.3390/molecules21040417 - 8 Apr 2016

Cited by 12 | Viewed by 6883

Abstract

Uridine-cytidine kinase 2 is implicated in uncontrolled proliferation of abnormal cells and it is a hallmark of cancer, therefore, there is need for effective inhibitors of this key enzyme. In this study, we employed the used of in silico studies to find effective [...] Read more.

Uridine-cytidine kinase 2 is implicated in uncontrolled proliferation of abnormal cells and it is a hallmark of cancer, therefore, there is need for effective inhibitors of this key enzyme. In this study, we employed the used of in silico studies to find effective UCK2 inhibitors of natural origin using bioinformatics tools. An in vitro kinase assay was established by measuring the amount of ADP production in the presence of ATP and 5-fluorouridine as a substrate. Molecular docking studies revealed an interesting ligand interaction with the UCK2 protein for both flavokawain B and alpinetin. Both compounds were found to reduce ADP production, possibly by inhibiting UCK2 activity in vitro. In conclusion, we have identified flavokawain B and alpinetin as potential natural UCK2 inhibitors as determined by their interactions with UCK2 protein using in silico molecular docking studies. This can provide information to identify lead candidates for further drug design and development. Full article

(This article belongs to the Section Natural Products Chemistry)

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11 pages, 3063 KiB

Open AccessArticle

Bryonolic Acid, a Triterpenoid, Protect Against N-methyl-d-Aspartate-Induced Neurotoxicity in PC12 Cells

by Jinhua Que, Miao Ye, Yuqin Zhang, Wen Xu, Huang Li, Wei Xu and Kedan Chu

Molecules 2016, 21(4), 418; https://doi.org/10.3390/molecules21040418 - 28 Mar 2016

Cited by 12 | Viewed by 6140

Abstract

Calcium overload is considered to be one of the mechanisms of cerebral ischemia. Ca²⁺ influx and Ca²⁺/calmodulin-dependent protein kinase II (CaMKII) and cAMP response element-binding protein (CREB) phosphorylation are considered to be involved in N-Methyl-d-aspartate (NMDA)-induced apoptosis [...] Read more.

Calcium overload is considered to be one of the mechanisms of cerebral ischemia. Ca²⁺ influx and Ca²⁺/calmodulin-dependent protein kinase II (CaMKII) and cAMP response element-binding protein (CREB) phosphorylation are considered to be involved in N-Methyl-d-aspartate (NMDA)-induced apoptosis process. This study investigated the neuroprotective effects of bryonolic acid (BA) in an NMDA-induced rat adrenal pheochromocytoma cell line (PC12) cells and the potential mechanism. PC12 was treated by NMDA to establish an excitotoxicity model. BA (110,100 and 1000 μM final concentration) was added to the medium 24 h prior to the addition of NMDA. Subsequently, a methyl thiazolyl tetrazolium (MTT) assay and a lactate dehydrogenase (LDH) release were performed. Ca²⁺ concentration was demonstrated using a scanning-dual wavelength fluorimetric method. In addition, protein and mRNA levels were determined via Western blot and real-time PCR. In the presence of BA, MTT assay and LDH assay showed that more cells were viable in comparison with the NMDA group. Moreover, the concentration of Ca²⁺ decreased with the addition of BA in culture. Furthermore, BA could upregulate protein expressions of Bcl-2, p-CREB, and p-CaMKII and downregulate protein expression of Bax. The mRNA results showed that the pattern of mRNA expression were similar to their respective protein levels. All these results indicate that BA protected PC12 cells against NMDA-induced apoptosis by inhibiting Ca²⁺ influx and regulating gene expression in the Ca²⁺-CaMKII-CREB signal pathway. Therefore, the present study supports the notion that BA may be a promising neuroprotective agent for the treatment of cerebral ischemia disease. Full article

(This article belongs to the Collection Triterpenes and Triterpenoids)

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14 pages, 948 KiB

Open AccessArticle

Antibacterial Properties and Effects of Fruit Chilling and Extract Storage on Antioxidant Activity, Total Phenolic and Anthocyanin Content of Four Date Palm (Phoenix dactylifera) Cultivars

by Muhammad Azizan Samad, Siti Hajar Hashim, Khanom Simarani and Jamilah Syafawati Yaacob

Molecules 2016, 21(4), 419; https://doi.org/10.3390/molecules21040419 - 26 Mar 2016

Cited by 88 | Viewed by 9552

Abstract

Phoenix dactylifera or date palm fruits are reported to contain natural compounds that exhibit antioxidant and antibacterial properties. This research aimed to study the effect of fruit chilling at 4 °C for 8 weeks, extract storage at −20 °C for 5 weeks, and [...] Read more.

Phoenix dactylifera or date palm fruits are reported to contain natural compounds that exhibit antioxidant and antibacterial properties. This research aimed to study the effect of fruit chilling at 4 °C for 8 weeks, extract storage at −20 °C for 5 weeks, and extraction solvents (methanol or acetone) on total phenolic content (TPC), antioxidant activity and antibacterial properties of Saudi Arabian P. dactylifera cv Mabroom, Safawi and Ajwa, as well as Iranian P. dactylifera cv Mariami. The storage stability of total anthocyanin content (TAC) was also evaluated, before and after storing the extracts at −20 °C and 4 °C respectively, for 5 weeks. Mariami had the highest TAC (3.18 ± 1.40 mg cyd 3-glu/100 g DW) while Mabroom had the lowest TAC (0.54 ± 0.15 mg cyd 3-glu/100 g DW). The TAC of all extracts increased after storage. The chilling of date palm fruits for 8 weeks prior to solvent extraction elevated the TPC of all date fruit extracts, except for methanolic extracts of Mabroom and Mariami. All IC₅₀ values of all cultivars decreased after the fruit chilling treatment. Methanol was a better solvent compared to acetone for the extraction of phenolic compounds in dates. The TPC of all cultivars extracts decreased after 5 weeks of extract storage. IC₅₀ values of all cultivars extracts increased after extract storage except for the methanolic extracts of Safawi and Ajwa. Different cultivars exhibited different antibacterial properties. Only the methanolic extract of Ajwa exhibited antibacterial activity against all four bacteria tested: Staphylococcus aureus, Bacillus cereus, Serratia marcescens and Escherichia coli. These results could be useful to the nutraceutical and pharmaceutical industries in the development of natural compound-based products. Full article

(This article belongs to the Section Natural Products Chemistry)

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14 pages, 888 KiB

Open AccessArticle

Hybrid Compounds Strategy in the Synthesis of Oleanolic Acid Skeleton-NSAID Derivatives

by Anna Pawełczyk, Dorota Olender, Katarzyna Sowa-Kasprzak and Lucjusz Zaprutko

Molecules 2016, 21(4), 420; https://doi.org/10.3390/molecules21040420 - 12 Apr 2016

Cited by 25 | Viewed by 6892

Abstract

The current study focuses on the synthesis of several hybrid individuals combining a natural oleanolic acid skeleton and synthetic nonsteroidal anti-inflammatory drug moieties (NSAIDs). It studied structural modifications of the oleanolic acid structure by use of the direct reactivity of hydroxyl or hydroxyimino [...] Read more.

The current study focuses on the synthesis of several hybrid individuals combining a natural oleanolic acid skeleton and synthetic nonsteroidal anti-inflammatory drug moieties (NSAIDs). It studied structural modifications of the oleanolic acid structure by use of the direct reactivity of hydroxyl or hydroxyimino groups at position C-3 of the triterpenoid skeleton with the carboxylic function of anti-inflammatory drugs leading to new perspective compounds with high potential pharmacological activities. Novel ester- and iminoester-type derivatives of oleanolic unit with the different NSAIDs, such as ibuprofen, aspirin, naproxen, and ketoprofen, were obtained and characterized. Moreover, preliminary research of compounds obtaining structure stability under acidic conditions was examined and the PASS method of prediction of activity spectra for substances was used to estimate the potential biological activity of these compounds. Full article

(This article belongs to the Section Organic Chemistry)

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13 pages, 3666 KiB

Open AccessArticle

Antioxidant and Anti-Inflammatory Effects of Chaenomeles sinensis Leaf Extracts on LPS-Stimulated RAW 264.7 Cells

by Young-Ki Han, Yon-Suk Kim, Sithranga Boopathy Natarajan, Won-Suk Kim, Jin-Woo Hwang, Nam-Joo Jeon, Jae-Hyun Jeong, Sang-Ho Moon, Byong-Tae Jeon and Pyo-Jam Park

Molecules 2016, 21(4), 422; https://doi.org/10.3390/molecules21040422 - 28 Mar 2016

Cited by 34 | Viewed by 7592

Abstract

The fruit of Chaenomeles sinensis has been traditionally used in ethnomedicine for the treatment of various human ailments, including pneumonia, bronchitis, and so on, but the pharmacological applications of the leaf part of the plant have not been studied. In this study, we [...] Read more.

The fruit of Chaenomeles sinensis has been traditionally used in ethnomedicine for the treatment of various human ailments, including pneumonia, bronchitis, and so on, but the pharmacological applications of the leaf part of the plant have not been studied. In this study, we evaluated the various radical scavenging activities and anti-inflammatory effects of different Chaenomeles sinensis leaf (CSL) extracts. The water extract showed a higher antioxidant and radical scavenging activities. However the ethanolic extracts showed higher NO scavenging activity than water extract, therefore the ethanolic extract of CSL was examined for anti-inflammatory effects on lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. The 70% ethanol extract of CSL (CSLE) has higher anti-inflammatory activity and significantly inhibited the production of nitric oxide (NO), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). In addition, CSLE suppressed LPS-stimulated inducible nitric oxide synthase (iNOS) and NO production, IL-1β and phospho-STAT1 expression. In this study, we investigated the effect of CSLE on the production of inflammatory mediators through the inhibition of the TRIF-dependent pathways. Furthermore, we evaluated the role of CSLE on LPS-induced expression of pro-inflammatory cytokines, such as TNF-α, IL-1β and IL-6. Our results suggest that CSLE attenuates the LPS-stimulated inflammatory responses in macrophages through regulating the key inflammatory mechanisms, providing scientific support for its traditional uses in treating various inflammatory diseases. Full article

(This article belongs to the Section Medicinal Chemistry)

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12 pages, 778 KiB

Open AccessArticle

GC×GC-TOFMS Analysis of Essential Oils Composition from Leaves, Twigs and Seeds of Cinnamomum camphora L. Presl and Their Insecticidal and Repellent Activities

by Hao Jiang, Jin Wang, Li Song, Xianshuang Cao, Xi Yao, Feng Tang and Yongde Yue

Molecules 2016, 21(4), 423; https://doi.org/10.3390/molecules21040423 - 28 Mar 2016

Cited by 109 | Viewed by 8720

Abstract

Interest in essential oils with pesticidal activity against insects and pests is growing. In this study, essential oils from different parts (leaves, twigs and seeds) of Cinnamomum camphora L. Presl were investigated for their chemical composition, and insecticidal and repellent activities against the [...] Read more.

Interest in essential oils with pesticidal activity against insects and pests is growing. In this study, essential oils from different parts (leaves, twigs and seeds) of Cinnamomum camphora L. Presl were investigated for their chemical composition, and insecticidal and repellent activities against the cotton aphid. The essential oils, obtained by hydrodistillation, were analyzed by GC×GC-TOFMS. A total of 96 components were identified in the essential oils and the main constituents found in the leaves and twigs were camphor, eucalyptol, linalool and 3,7-dimethyl-1,3,7-octatriene. The major components found in the seeds were eucalyptol (20.90%), methyleugenol (19.98%), linalool (14.66%) and camphor (5.5%). In the contact toxicity assay, the three essential oils of leaves, twigs and seeds exhibited a strong insecticidal activity against cotton aphids with LC₅₀ values of 245.79, 274.99 and 146.78 mg/L (after 48 h of treatment), respectively. In the repellent assay, the highest repellent rate (89.86%) was found in the seed essential oil at the concentration of 20 μL/mL after 24 h of treatment. Linalool was found to be a significant contributor to the insecticidal and repellent activities. The results indicate that the essential oils of C. camphora might have the potential to be developed into a natural insecticide or repellent for controlling cotton aphids. Full article

(This article belongs to the Section Natural Products Chemistry)

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6 pages, 704 KiB

Open AccessArticle

Preliminary LC-MS Based Screening for Inhibitors of Plasmodium falciparum Thioredoxin Reductase (PfTrxR) among a Set of Antimalarials from the Malaria Box

by Neil K. Tiwari, Priscilla J. Reynolds and Angela I. Calderón

Molecules 2016, 21(4), 424; https://doi.org/10.3390/molecules21040424 - 28 Mar 2016

Cited by 12 | Viewed by 6232

Abstract

Plasmodium falciparum thioredoxin reductase (PfTrxR) has been identified as a potential drug target to combat growing antimalarial drug resistance. Medicines for Malaria Venture (MMV) has pre-screened and identified a set of 400 antimalarial compounds called the Malaria Box. From those, we [...] Read more.

Plasmodium falciparum thioredoxin reductase (PfTrxR) has been identified as a potential drug target to combat growing antimalarial drug resistance. Medicines for Malaria Venture (MMV) has pre-screened and identified a set of 400 antimalarial compounds called the Malaria Box. From those, we have evaluated their mechanisms of action through inhibition of PfTrxR and found new active chemical scaffolds. Five compounds with significant PfTrxR inhibitory activity, with IC₅₀ values ranging from 0.9–7.5 µM against the target enzyme, were found out of the Malaria Box. Full article

(This article belongs to the Special Issue Thioredoxin and Glutathione Systems)

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13 pages, 1796 KiB

Open AccessArticle

Aroylhydrazone Cu(II) Complexes in keto Form: Structural Characterization and Catalytic Activity towards Cyclohexane Oxidation

by Manas Sutradhar, Elisabete C. B. A. Alegria, M. Fátima C. Guedes da Silva, Luísa M. D. R. S. Martins and Armando J. L. Pombeiro

Molecules 2016, 21(4), 425; https://doi.org/10.3390/molecules21040425 - 29 Mar 2016

Cited by 30 | Viewed by 7168

Abstract

The reaction of the Schiff base (3,5-di-tert-butyl-2-hydroxybenzylidene)-2-hydroxybenzohydrazide (H₃L) with a copper(II) salt of a base of a strong acid, i.e., nitrate, chloride or sulphate, yielded the mononuclear complexes [Cu(H₂L)(NO₃)(H₂O)] (1), [Cu(H₂ [...] Read more.

The reaction of the Schiff base (3,5-di-tert-butyl-2-hydroxybenzylidene)-2-hydroxybenzohydrazide (H₃L) with a copper(II) salt of a base of a strong acid, i.e., nitrate, chloride or sulphate, yielded the mononuclear complexes [Cu(H₂L)(NO₃)(H₂O)] (1), [Cu(H₂L)Cl]·2MeOH (2) and the binuclear complex [{Cu(H₂L)}₂(µ-SO₄)]·2MeOH (3), respectively, with H₂L⁻ in the keto form. Compounds 1–3 were characterized by elemental analysis, Infrared (IR) spectroscopy, Electrospray Ionisation Mass Spectrometry (ESI-MS) and single crystal X-ray crystallography. All compounds act as efficient catalysts towards the peroxidative oxidation of cyclohexane to cyclohexyl hydroperoxide, cyclohexanol and cyclohexanone, under mild conditions. In the presence of an acid promoter, overall yields (based on the alkane) up to 25% and a turnover number (TON) of 250 (TOF of 42 h⁻¹) after 6 h, were achieved. Full article

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

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13 pages, 3230 KiB

Open AccessArticle

Yeast Extract and Silver Nitrate Induce the Expression of Phenylpropanoid Biosynthetic Genes and Induce the Accumulation of Rosmarinic Acid in Agastache rugosa Cell Culture

by Woo Tae Park, Mariadhas Valan Arasu, Naif Abdullah Al-Dhabi, Sun Kyung Yeo, Jin Jeon, Jong Seok Park, Sook Young Lee and Sang Un Park

Molecules 2016, 21(4), 426; https://doi.org/10.3390/molecules21040426 - 29 Mar 2016

Cited by 65 | Viewed by 7768

Abstract

The present study aimed to investigate the role of yeast extract and silver nitrate on the enhancement of phenylpropanoid pathway genes and accumulation of rosmarinic acid in Agastache rugosa cell cultures. The treatment of cell cultures with yeast extract (500 mg/L) and silver [...] Read more.

The present study aimed to investigate the role of yeast extract and silver nitrate on the enhancement of phenylpropanoid pathway genes and accumulation of rosmarinic acid in Agastache rugosa cell cultures. The treatment of cell cultures with yeast extract (500 mg/L) and silver nitrate (30 mg/L) for varying times enhanced the expression of genes in the phenylpropanoid pathway and the production of rosmarinic acid. The results indicated that the expression of RAS and HPPR was proportional to the amount of yeast extract and silver nitrate. The transcript levels of HPPR under yeast extract treatment were 1.84-, 1.97-, and 2.86-fold higher than the control treatments after 3, 6, and 12 h, respectively, whereas PAL expression under silver nitrate treatment was 52.31-fold higher than in the non-treated controls after 24 h of elicitation. The concentration of rosmarinic acid was directly proportional to the concentration of the applied elicitors. Yeast extract supplementation documented the highest amount of rosmarinic acid at 4.98 mg/g, whereas silver nitrate addition resulted in a comparatively lower amount of rosmarinic acid at 0.65 mg/g. In conclusion, addition of yeast extract to the cell cultures enhanced the accumulation of rosmarinic acid, which was evidenced by the expression levels of the phenylpropanoid biosynthetic pathway genes in A. rugosa. Full article

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

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16 pages, 22885 KiB

Open AccessArticle

Effect of Different Pretreatment Methods on Birch Outer Bark: New Biorefinery Routes

by Anthi Karnaouri, Ulrika Rova and Paul Christakopoulos

Molecules 2016, 21(4), 427; https://doi.org/10.3390/molecules21040427 - 30 Mar 2016

Cited by 25 | Viewed by 7210

Abstract

A comparative study among different pretreatment methods used for the fractionation of the birch outer bark components, including steam explosion, hydrothermal and organosolv treatments based on the use of ethanol/water media, is reported. The residual solid fractions have been characterized by ATR-FTIR, ¹³ [...] Read more.

A comparative study among different pretreatment methods used for the fractionation of the birch outer bark components, including steam explosion, hydrothermal and organosolv treatments based on the use of ethanol/water media, is reported. The residual solid fractions have been characterized by ATR-FTIR, ¹³C-solid-state NMR and morphological alterations after pretreatment were detected by scanning electron microscopy. The general chemical composition of the untreated and treated bark including determination of extractives, suberin, lignin and monosaccharides was also studied. Composition of the residual solid fraction and relative proportions of different components, as a function of the processing conditions, could be established. Organosolv treatment produces a suberin-rich solid fraction, while during hydrothermal and steam explosion treatment cleavage of polysaccharide bonds occurs. This work will provide a deeper fundamental knowledge of the bark chemical composition, thus increasing the utilization efficiency of birch outer bark and may create possibilities to up-scale the fractionation processes. Full article

(This article belongs to the Section Natural Products Chemistry)

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7 pages, 848 KiB

Open AccessArticle

Nanoparticle Effects on Human Platelets in Vitro: A Comparison between PAMAM and Triazine Dendrimers

by Alan E. Enciso, Barry Neun, Jamie Rodriguez, Amalendu P. Ranjan, Marina A. Dobrovolskaia and Eric E. Simanek

Molecules 2016, 21(4), 428; https://doi.org/10.3390/molecules21040428 - 29 Mar 2016

Cited by 48 | Viewed by 5985

Abstract

Triazine and PAMAM dendrimers of similar size and number of cationic surface groups were compared for their ability to promote platelet aggregation. Triazine dendrimers (G3, G5 and G7) varied in molecular weight from 8 kDa–130 kDa and in surface groups 16–256. PAMAM dendrimers [...] Read more.

Triazine and PAMAM dendrimers of similar size and number of cationic surface groups were compared for their ability to promote platelet aggregation. Triazine dendrimers (G3, G5 and G7) varied in molecular weight from 8 kDa–130 kDa and in surface groups 16–256. PAMAM dendrimers selected for comparison included G3 (7 kDa, 32 surface groups) and G6 (58 kDa, 256 surface groups). The treatment of human platelet-rich plasma (PRP) with low generation triazine dendrimers (0.01–1 µM) did not show any significant effect in human platelet aggregation in vitro; however, the treatment of PRP with larger generations promotes an effective aggregation. These results are in agreement with studies performed with PAMAM dendrimers, where large generations promote aggregation. Triazine dendrimers promote aggregation less aggressively than PAMAM dendrimers, a factor attributed to differences in cationic charge or the formation of supramolecular assemblies of dendrimers. Full article

(This article belongs to the Special Issue Functional Dendrimers)

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14 pages, 620 KiB

Open AccessArticle

Furostanol and Spirostanol Saponins from Tribulus terrestris

by Zhen-Fang Wang, Bing-Bing Wang, Yang Zhao, Fang-Xu Wang, Yan Sun, Rui-Jie Guo, Xin-Bo Song, Hai-Li Xin and Xin-Guang Sun

Molecules 2016, 21(4), 429; https://doi.org/10.3390/molecules21040429 - 30 Mar 2016

Cited by 29 | Viewed by 12017

Abstract

Twelve new steroidal saponins, including eleven furostanol saponins, terrestrinin J–T (1–11), and one spirostanol saponin, terrestrinin U (12), together with seven known steroidal saponins 13–19 were isolated from T. terrestris. The structures of the [...] Read more.

Twelve new steroidal saponins, including eleven furostanol saponins, terrestrinin J–T (1–11), and one spirostanol saponin, terrestrinin U (12), together with seven known steroidal saponins 13–19 were isolated from T. terrestris. The structures of the new compounds were established on the basis of spectroscopic data, including 1D and 2D NMR and HRESIMS, and comparisons with published data. Full article

(This article belongs to the Section Natural Products Chemistry)

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15 pages, 1637 KiB

Open AccessArticle

Comparison of Anti-Oxidant and Anti-Inflammatory Effects between Fresh and Aged Black Garlic Extracts

by Yi Yeong Jeong, Ji Hyeon Ryu, Jung-Hye Shin, Min Jung Kang, Jae Ran Kang, Jaehee Han and Dawon Kang

Molecules 2016, 21(4), 430; https://doi.org/10.3390/molecules21040430 - 30 Mar 2016

Cited by 110 | Viewed by 17430

Abstract

Numerous studies have demonstrated that aged black garlic (ABG) has strong anti-oxidant activity. Little is known however regarding the anti-inflammatory activity of ABG. This study was performed to identify and compare the anti-oxidant and anti-inflammatory effects of ABG extract (ABGE) with those of [...] Read more.

Numerous studies have demonstrated that aged black garlic (ABG) has strong anti-oxidant activity. Little is known however regarding the anti-inflammatory activity of ABG. This study was performed to identify and compare the anti-oxidant and anti-inflammatory effects of ABG extract (ABGE) with those of fresh raw garlic (FRG) extract (FRGE). In addition, we investigated which components are responsible for the observed effects. Hydrogen peroxide (H₂O₂) and lipopolysaccharide (LPS) were used as a pro-oxidant and pro-inflammatory stressor, respectively. ABGE showed high ABTS and DPPH radical scavenging activities and low ROS generation in RAW264.7 cells compared with FRGE. However, inhibition of cyclooxygenase-2 and 5-lipooxygenase activities by FRGE was stronger than that by ABGE. FRGE reduced PGE₂, NO, IL-6, IL-1β, LTD₄, and LTE₄ production in LPS-activated RAW264.7 cells more than did ABGE. The combination of FRGE and sugar (galactose, glucose, fructose, or sucrose), which is more abundant in ABGE than in FRGE, decreased the anti-inflammatory activity compared with FRGE. FRGE-induced inhibition of NF-κB activation and pro-inflammatory gene expression was blocked by combination with sugars. The lower anti-inflammatory activity in ABGE than FRGE could result from the presence of sugars. Our results suggest that ABGE might be helpful for the treatment of diseases mediated predominantly by ROS. Full article

(This article belongs to the Section Natural Products Chemistry)

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16 pages, 2293 KiB

Open AccessArticle

Phenolic and Chromatic Properties of Beibinghong Red Ice Wine during and after Vinification

by Jin-Chen Li, Si-Yu Li, Fei He, Zheng-Yi Yuan, Tao Liu, Malcolm J. Reeves and Chang-Qing Duan

Molecules 2016, 21(4), 431; https://doi.org/10.3390/molecules21040431 - 20 Apr 2016

Cited by 16 | Viewed by 6654

Abstract

The phenolic and chromatic characteristics of a special red ice wine made from a Vitis amurensis × V. vinifera hybrid cultivar Beibinghong were studied. Results from two different vintages (2013 and 2014) showed that during vinification, the phenolic acid content increased, while the [...] Read more.

The phenolic and chromatic characteristics of a special red ice wine made from a Vitis amurensis × V. vinifera hybrid cultivar Beibinghong were studied. Results from two different vintages (2013 and 2014) showed that during vinification, the phenolic acid content increased, while the level of flavonoids (flavonols, flavan-3-ols, and anthocyanins) reduced by a variable extent. The color intensity and red % decreased together with a decrease in anthocyanin content. This was accompanied by an increase in hue as well as yellow %. The final phenolic content was found to be between 119.54 and 180.93 mg/L, with anthocyanins as the predominant phenolic group (92.06%–93.03%), of which 3,5-O-diglucosidic anthocyanins made up 53.55%–79.04%. Phenolic acids were the primary non-anthocyanin phenolics at about 6.64%–7.5%. The phenolic contents and color parameters of Beibinghong dry red wine and several V. vinifera dry red wines of superior color quality were also used in an attempt to clarify the relationship between phenolics and color in the Beibinghong red ice wine. By using Pearson correlation analysis and principal component analysis (PCA), it was found that 3,5-O-diglucosidic anthocyanins and protocatechuic acid were the only characteristic phenolics that differentiated Beibinghong wines from the other selected red wines from more traditional varieties. They were also the main phenolics to be positively correlated with the hue and yellow % of the wine at the early stages leading into maturation. Their presence might, therefore, explain the relatively high hue and yellow % of Beibinghong ice wine. Full article

(This article belongs to the Collection Wine Chemistry)

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13 pages, 1158 KiB

Open AccessArticle

On the High Sensitivity of the Electronic States of 1 nm Gold Particles to Pretreatments and Modifiers

by Oxana Martynyuk, Yulia Kotolevich, Rodrigo Vélez, Jesus Efren Cabrera Ortega, Hugo Tiznado, Trino Zepeda Partida, Josué D. Mota-Morales, Alexey Pestryakov and Nina Bogdanchikova

Molecules 2016, 21(4), 432; https://doi.org/10.3390/molecules21040432 - 31 Mar 2016

Cited by 8 | Viewed by 6967

Abstract

In this paper, the effect of modifiers and pretreatments on the electronic states of 1 nm gold nanoparticles (AuNPs) supported on silica was systematically studied. AuNPs deposited on silica (particle size of 2–4 nm) modified with Ce, La and Fe oxides, were studied [...] Read more.

In this paper, the effect of modifiers and pretreatments on the electronic states of 1 nm gold nanoparticles (AuNPs) supported on silica was systematically studied. AuNPs deposited on silica (particle size of 2–4 nm) modified with Ce, La and Fe oxides, were studied by FTIR of adsorbed CO after different redox treatments at 100, 300 and 500 °C. This study was conducted at room temperature to allow detecting the electronic states of gold, which is more likely involved in CO oxidation at the same temperature. AuNP size distribution was measured by HRTEM. It is shown that the electronic state of gold species (Au_n^δ−, Au⁰, Au_n^δ+, Au⁺) in 1 nm AuNPs is sensitive to the modifier as well as to the temperatures of redox pretreatments. Supports modified with the same additives but containing larger AuNPs (~3, 4, 5, and 7 nm) were also studied. They showed that Au⁰ remains stable irrespective of additives and redox pretreatments, indicating no significant effect of such treatments on the electronic properties of larger AuNPs. Samples with a predominant AuNP size of 2 nm are an intermediate case between these two groups of materials. Full article

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

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22 pages, 5537 KiB

Open AccessArticle

Synthesis and Structure-Activity Relationship Analysis of 5-HT₇ Receptor Antagonists: Piperazin-1-yl Substituted Unfused Heterobiaryls

by Lucjan Strekowski, Jarosław Sączewski, Elizabeth A. Raux, Nilmi T. Fernando, Jeff Klenc, Shirish Paranjpe, Aldona Raszkiewicz, Ava L. Blake, Adam J. Ehalt, Samuel Barnes, Timothy C. Baranowski, Shannon M. Sullivan, Grzegorz Satała and Andrzej J. Bojarski

Molecules 2016, 21(4), 433; https://doi.org/10.3390/molecules21040433 - 31 Mar 2016

Cited by 5 | Viewed by 8078

Abstract

A series of piperazin-1-yl substituted unfused heterobiaryls was synthesized as ligands of the 5-HT₇ receptors. The goal of this project was to elucidate the structural features that affect the 5-HT₇ binding affinity of this class of compounds represented by the model [...] Read more.

A series of piperazin-1-yl substituted unfused heterobiaryls was synthesized as ligands of the 5-HT₇ receptors. The goal of this project was to elucidate the structural features that affect the 5-HT₇ binding affinity of this class of compounds represented by the model ligand 4-(3-furyl)-2-(4-methylpiperazin-1-yl)pyrimidine (2). The SAR studies included systematical structural changes of the pyrimidine core moiety in 2 to quinazoline, pyridine and benzene, changes of the 3-furyl group to other heteroaryl substituents, the presence of various analogs of the 4-methylpiperazin-1-yl group, as well as additional substitutions at positions 5 and 6 of the pyrimidine. Substitution of position 6 of the pyrimidine in the model ligand with an alkyl group results in a substantial increase of the binding affinity (note a change in position numbers due to the nomenclature rules). It was also demonstrated that 4-(3-furyl) moiety is crucial for the 5-HT₇ binding affinity of the substituted pyrimidines, although, the pyrimidine core can be replaced with a pyridine ring without a dramatic loss of the binding affinity. The selected ethylpyrimidine (12) and butylpyrimidine (13) analogs of high 5-HT₇ binding affinity showed antagonistic properties in cAMP functional test and varied selectivity profile—compound 12 can be regarded as a dual 5-HT₇/5-HT_2AR ligand, and 13 as a multi-receptor (5-HT₇, 5-HT_2A, 5-HT₆ and D₂) agent. Full article

(This article belongs to the Section Medicinal Chemistry)

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7 pages, 929 KiB

Open AccessArticle

Labdane Diterpenes from the Fruits of Sinopodophyllum emodi

by Yan-Jun Sun, Mei-Ling Gao, Yan-Li Zhang, Jun-Min Wang, Ya Wu, Yu Wang and Tao Liu

Molecules 2016, 21(4), 434; https://doi.org/10.3390/molecules21040434 - 31 Mar 2016

Cited by 8 | Viewed by 5320

Abstract

Two new labdane diterpenes, sinoditerpene A (1) and B (2), were isolated from the fruits of Sinopodophyllum emodi, along with two known analogues 3 and 4. Their structures were established on the basis of extensive spectroscopic analysis. The isolation of compounds 1–4 [...] Read more.

Two new labdane diterpenes, sinoditerpene A (1) and B (2), were isolated from the fruits of Sinopodophyllum emodi, along with two known analogues 3 and 4. Their structures were established on the basis of extensive spectroscopic analysis. The isolation of compounds 1–4 represents the first report of diterpenes from the genus Sinopodophyllum. The cytotoxic activities of all isolated compounds were evaluated in comparison with 5-fluorouracil against the MCF-7 and HepG2 cell lines, towards which 3 showed more potent cytotoxicity. Full article

(This article belongs to the Special Issue Diterpene and Its Significance in Natural Medicine)

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16 pages, 2103 KiB

Open AccessArticle

Dietary Nucleotides Supplementation and Liver Injury in Alcohol-Treated Rats: A Metabolomics Investigation

by Xiaxia Cai, Lei Bao, Nan Wang, Meihong Xu, Ruixue Mao and Yong Li

Molecules 2016, 21(4), 435; https://doi.org/10.3390/molecules21040435 - 31 Mar 2016

Cited by 29 | Viewed by 6590

Abstract

Background: Previous studies suggested that nucleotides were beneficial for liver function, lipid metabolism and so on. The present study aimed to investigate the metabolic response of dietary nucleotides supplementation in alcohol-induced liver injury rats. Methods: Five groups of male Wistar rats were used: [...] Read more.

Background: Previous studies suggested that nucleotides were beneficial for liver function, lipid metabolism and so on. The present study aimed to investigate the metabolic response of dietary nucleotides supplementation in alcohol-induced liver injury rats. Methods: Five groups of male Wistar rats were used: normal control group (basal diet, equivalent distilled water), alcohol control group (basal diet, 50% alcohol (v/v)), dextrose control group (basal diet, isocaloric amount of dextrose), and 0.04% and 0.16% nucleotides groups (basal diet supplemented with 0.4 g and 1.6 g nucleotides kg⁻¹ respectively, 50% alcohol (v/v)). The liver injury was measured through traditional liver enzymes, expression of oxidative stress markers and histopathological examination. Ultra-performance liquid chromatography quadrupole-time-flight mass spectrometry (UPLC-Q-TOF-MS) was applied to identify liver metabolite profiles. Results: Nucleotides supplementation prevented the progression of hepatocyte steatosis. The levels of total proteins, globulin, alanine aminotransferase, aspartate aminotransferase, total cholesterol triglyceride, as well as the oxidative stress markers altered by alcohol, were improved by nucleotides supplementation. Elevated levels of liver bile acids (glycocholic acid, chenodeoxyglycocholic acid, and taurodeoxycholic acid), as well as lipids (stearic acid, palmitic acid, oleic acid, phosphatidylcholine, and lysophosphatidylethanolamine) in alcohol-treated rats were reversed by nucleotides supplementation. In addition, supplementation with nucleotides could increase the levels of amino acids, including valyl-Leucine, l-leucine, alanyl-leucine and l-phenylalanine. Conclusion: These data indicate potential biomarkers and confirm the benefit of dietary nucleotides on alcoholic liver injury. Full article

(This article belongs to the Section Metabolites)

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11 pages, 2394 KiB

Open AccessArticle

sym-Trisubstituted 1,3,5-Triazine Derivatives as Promising Organic Corrosion Inhibitors for Steel in Acidic Solution

by Ayman El-Faham, Kholood A. Dahlous, Zeid A. AL Othman, Hamad A. Al-Lohedan and Gamal A. El-Mahdy

Molecules 2016, 21(4), 436; https://doi.org/10.3390/molecules21040436 - 31 Mar 2016

Cited by 32 | Viewed by 6587

Abstract

Triazine derivatives, namely, 2,4,6-tris(quinolin-8-yloxy)-1,3,5-triazine (T3Q), N²,N⁴,N⁶-tris(pyridin-2-ylmethyl)-1,3,5-triazine-2,4,6-triamine (T3AMPy) and 2,2′,2′′-[(1,3,5-triazine-2,4,6-triyl)tris(azanediyl)] tris(ethan-1-ol) (T3EA) were synthesized and their inhibition of steel corrosion in hydrochloric acid solution was investigated using electrochemical techniques. The corrosion protection of the prepared compounds increased with [...] Read more.

Triazine derivatives, namely, 2,4,6-tris(quinolin-8-yloxy)-1,3,5-triazine (T3Q), N²,N⁴,N⁶-tris(pyridin-2-ylmethyl)-1,3,5-triazine-2,4,6-triamine (T3AMPy) and 2,2′,2′′-[(1,3,5-triazine-2,4,6-triyl)tris(azanediyl)] tris(ethan-1-ol) (T3EA) were synthesized and their inhibition of steel corrosion in hydrochloric acid solution was investigated using electrochemical techniques. The corrosion protection of the prepared compounds increased with increasing concentration and reached up to 98% at 250 ppm. The adsorption of T3Q, T3AMPy, and T3EA on the steel surface was in accordance with the Langmuir adsorption isotherm. The electrochemical results revealed that T3Q, T3AMPy and T3EA act as excellent organic inhibitors and can labeled as mixed type inhibitors. The efficiencies of the tested compounds were affected by the nature of the side chain present in the triazine ring, where T3EA gave the least inhibition while T3Q and T3AMPy gave higher and almost the same inhibition effects. The inhibition efficiencies obtained from the different electrochemical techniques were in good agreement. Full article

(This article belongs to the Section Organic Chemistry)

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17 pages, 2436 KiB

Open AccessArticle

Identification of Oxygenated Fatty Acid as a Side Chain of Lipo-Alkaloids in Aconitum carmichaelii by UHPLC-Q-TOF-MS and a Database

by Ying Liang, Jian-Lin Wu, Elaine Lai-Han Leung, Hua Zhou, Zhongqiu Liu, Guanyu Yan, Ying Liu, Liang Liu and Na Li

Molecules 2016, 21(4), 437; https://doi.org/10.3390/molecules21040437 - 31 Mar 2016

Cited by 19 | Viewed by 7737

Abstract

Lipo-alkaloid is a kind of C19-norditerpenoid alkaloid usually found in Aconitum species. Structurally, they contain an aconitane skeleton and one or two fatty acid moieties of 3–25 carbon chains with 1–6 unsaturated degrees. Analysis of the lipo-alkaloids in roots of Aconitum carmichaelii resulted [...] Read more.

Lipo-alkaloid is a kind of C19-norditerpenoid alkaloid usually found in Aconitum species. Structurally, they contain an aconitane skeleton and one or two fatty acid moieties of 3–25 carbon chains with 1–6 unsaturated degrees. Analysis of the lipo-alkaloids in roots of Aconitum carmichaelii resulted in the isolation of six known pure lipo-alkaloids (A1–A6) and a lipo-alkaloid mixture (A7). The mixture shared the same aconitane skeleton of 14-benzoylmesaconine, but their side chains were determined to be 9-hydroxy-octadecadienoic acid, 13-hydroxy-octadecadienoic acid and 10-hydroxy-octadecadienoic acid, respectively, by MS/MS analysis after alkaline hydrolysis. To our knowledge, this is the first time of the reporting of the oxygenated fatty acids as the side chains in naturally-occurring lipo-alkaloids. In order to identify more lipo-alkaloids, a compound database was established based on various combinations between the aconitane skeleton and the fatty acid chain, and then, the identification of lipo-alkaloids was conducted using the database, UHPLC-Q-TOF-MS and MS/MS. Finally, 148 lipo-alkaloids were identified from A. carmichaelii after intensive MS/MS analysis, including 93 potential new compounds and 38 compounds with oxygenated fatty acid moieties. Full article

(This article belongs to the Collection Herbal Medicine Research)

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14 pages, 3952 KiB

Open AccessArticle

Analysis of Potential Amino Acid Biomarkers in Brain Tissue and the Effect of Galangin on Cerebral Ischemia

by Ruocong Yang, Kun Chen, Yanyan Zhao, Pengpeng Tian, Feipeng Duan, Wenli Sun, Yuxin Liu, Zhiyong Yan and Shaojing Li

Molecules 2016, 21(4), 438; https://doi.org/10.3390/molecules21040438 - 6 Apr 2016

Cited by 18 | Viewed by 6250

Abstract

Galangin, a potent scavenger of free radicals, has been used as an herbal medicine for various ailments for centuries in Asia. With complex pathophysiology, ischemic stroke is one of the most frequent causes of death and disability worldwide. We have reported that galangin [...] Read more.

Galangin, a potent scavenger of free radicals, has been used as an herbal medicine for various ailments for centuries in Asia. With complex pathophysiology, ischemic stroke is one of the most frequent causes of death and disability worldwide. We have reported that galangin provides direct protection against ischemic injury as a potential neuroprotective agent and has potential therapeutic effects on the changes of serum amino acids in ischemic stroke; however, the mechanism of the changes of amino acids in the ischemic brain tissue has not yet been clarified. In this paper, we explored brain tissue amino acid biomarkers in the acute phase of cerebral ischemia and the effect of galangin on those potential biomarkers. Finally, we identified that glutamic acid, alanine and aspartic acid showed significant changes (p < 0.05 or p < 0.01) in galangin-treated groups compared with vehicle-treated rats and the four enzymes associated with these three AAs’ metabolic pathways; GLUD1, SLC16A10, SLC1A1 and GPT were identified by multiplex interactions with the three amino acids. By metabolite-protein network analysis and molecular docking, six of 28 proteins were identified and might become potential galangin biomarkers for acute ischemic stroke. The data in our study provides thoughts for exploring the mechanism of disease, discovering new targets for drug candidates and elucidating the related regulatory signal network. Full article

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

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12 pages, 1560 KiB

Open AccessArticle

Photophysical Characterization and in Vitro Phototoxicity Evaluation of 5,10,15,20-Tetra(quinolin-2-yl)porphyrin as a Potential Sensitizer for Photodynamic Therapy

by Letícia D. Costa, Joana De A. e Silva, Sofia M. Fonseca, Cláudia T. Arranja, Ana M. Urbano and Abilio J.F.N. Sobral

Molecules 2016, 21(4), 439; https://doi.org/10.3390/molecules21040439 - 31 Mar 2016

Cited by 29 | Viewed by 6676

Abstract

Photodynamic therapy (PDT) is a selective and minimally invasive therapeutic approach, involving the combination of a light-sensitive compound, called a photosensitizer (PS), visible light and molecular oxygen. The interaction of these per se harmless agents results in the production of reactive species. This [...] Read more.

Photodynamic therapy (PDT) is a selective and minimally invasive therapeutic approach, involving the combination of a light-sensitive compound, called a photosensitizer (PS), visible light and molecular oxygen. The interaction of these per se harmless agents results in the production of reactive species. This triggers a series of cellular events that culminate in the selective destruction of cancer cells, inside which the photosensitizer preferentially accumulates. The search for ideal PDT photosensitizers has been a very active field of research, with a special focus on porphyrins and porphyrin-related macrocycle molecules. The present study describes the photophysical characterization and in vitro phototoxicity evaluation of 5,10,15,20-tetra(quinolin-2-yl)porphyrin (2-TQP) as a potential PDT photosensitizer. Molar absorption coefficients were determined from the corresponding absorption spectrum, the fluorescence quantum yield was calculated using 5,10,15,20-tetraphenylporphyrin (TPP) as a standard and the quantum yield of singlet oxygen generation was determined by direct phosphorescence measurements. Toxicity evaluations (in the presence and absence of irradiation) were performed against HT29 colorectal adenocarcinoma cancer cells. The results from this preliminary study show that the hydrophobic 2-TQP fulfills several critical requirements for a good PDT photosensitizer, namely a high quantum yield of singlet oxygen generation (Φ_∆ 0.62), absence of dark toxicity and significant in vitro phototoxicity for concentrations in the micromolar range. Full article

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

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11 pages, 735 KiB

Open AccessCommunication

Novel Selective Butyrylcholinesterase Inhibitors Incorporating Antioxidant Functionalities as Potential Bimodal Therapeutics for Alzheimer’s Disease

by Mike Jones, Jun Wang, Shona Harmon, Beata Kling, Jörg Heilmann and John F. Gilmer

Molecules 2016, 21(4), 440; https://doi.org/10.3390/molecules21040440 - 1 Apr 2016

Cited by 20 | Viewed by 5809

Abstract

Isosorbide-2-carbamates-5-aryl esters are highly potent and very selective butyrylcholinesterase inhibitors. The objective of the present work was to address the hypothesis that the isosorbide-aryl-5-ester group could be replaced with an antioxidant functionality while maintaining inhibitor effects and selectivity. We successfully incorporated ferulic acid [...] Read more.

Isosorbide-2-carbamates-5-aryl esters are highly potent and very selective butyrylcholinesterase inhibitors. The objective of the present work was to address the hypothesis that the isosorbide-aryl-5-ester group could be replaced with an antioxidant functionality while maintaining inhibitor effects and selectivity. We successfully incorporated ferulic acid or lipoic acid groups producing potent selective inhibitors of butyrylcholinesterase (BuChE). The hybrid compounds were non-toxic to the murine hippocampal cell line HT-22 and lipoate esters were neuroprotective at 10 and 25 µM when the cells were challenged with glutamate (5 mM) in a similar manner to the positive control quercetin. The benzyl carbamate 7a was a potent inhibitor of BuChE (IC₅₀ 150 nM) and it was effective in reducing glutamate toxicity to neuronal cells at >5 µM. Representative compounds exhibited an antioxidant effect in the oxygen radical absorbance capacity assay as the lipoate 7d was not active, whereas the ferulate 8a showed a weak, but significant, activity with 0.635 ± 0.020 Trolox Equivalent. Full article

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

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12 pages, 1012 KiB

Open AccessArticle

A Novel and Efficient Five-Component Synthesis of Pyrazole Based Pyrido[2,3-d]pyrimidine-diones in Water: A Triply Green Synthesis

by Majid M. Heravi and Mansoureh Daraie

Molecules 2016, 21(4), 441; https://doi.org/10.3390/molecules21040441 - 1 Apr 2016

Cited by 45 | Viewed by 9494

Abstract

A novel one pot synthesis of pyrazolo[4′,3′:5,6]pyrido[2,3-d]pyrimidine-diones, via a five-component reaction, involving, hydrazine hydrate, ethyl acetoacetate, and 1,3-dimethyl barbituric acid, an appropriate aryl aldehydes and ammonium acetate catalyzed via both of heterogeneous and homogeneous catalysis in water, is reported. Full article

(This article belongs to the Special Issue MCRs and Related One-Pot Organic Synthesis)

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6 pages, 740 KiB

Open AccessArticle

Two Additional New Compounds from the Marine-Derived Fungus Pseudallescheria ellipsoidea F42-3

by Kun-Teng Wang, Meng-Yang Xu, Wei Liu, Hou-Jin Li, Jun Xu, De-Po Yang, Wen-Jian Lan and Lai-You Wang

Molecules 2016, 21(4), 442; https://doi.org/10.3390/molecules21040442 - 1 Apr 2016

Cited by 18 | Viewed by 5142

Abstract

Two additional new compounds, pseudellone D (1) and (5S,6S)-dihydroxylasiodiplodin (3), along with the two known compounds lasiodipline F (2), (5S)-hydroxylasiodiplodin (4) were isolated from the marine-derived fungus Pseudallescheria ellipsoidea F42-3 associated with the soft coral Lobophytum crassum [...] Read more.

Two additional new compounds, pseudellone D (1) and (5S,6S)-dihydroxylasiodiplodin (3), along with the two known compounds lasiodipline F (2), (5S)-hydroxylasiodiplodin (4) were isolated from the marine-derived fungus Pseudallescheria ellipsoidea F42-3 associated with the soft coral Lobophytum crassum. Their structures, including absolute configurations, were elucidated on the basis of the corresponding spectroscopic data and electronic circular dichroism (ECD) spectra. Full article

(This article belongs to the Section Natural Products Chemistry)

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10 pages, 2352 KiB

Open AccessArticle

Silymarin Prevents Restraint Stress-Induced Acute Liver Injury by Ameliorating Oxidative Stress and Reducing Inflammatory Response

by Sou Hyun Kim, Dal-Seok Oh, Ji Youn Oh, Tae Gen Son, Dong Yeon Yuk and Young-Suk Jung

Molecules 2016, 21(4), 443; https://doi.org/10.3390/molecules21040443 - 1 Apr 2016

Cited by 60 | Viewed by 9486

Abstract

Silymarin is a flavonoid extracted from the milk thistle Silybum marianum. It has been reported to prevent liver injuries induced by various chemicals or toxins. Our recent study suggested that silymarin induces hepatic synthesis of glutathione by increasing cysteine availability, which may [...] Read more.

Silymarin is a flavonoid extracted from the milk thistle Silybum marianum. It has been reported to prevent liver injuries induced by various chemicals or toxins. Our recent study suggested that silymarin induces hepatic synthesis of glutathione by increasing cysteine availability, which may consequently contribute to increased antioxidant capacity of the liver. In the present study, we investigated the effects of silymarin on acute liver injury induced by restraint stress. Silymarin (100 mg/kg) was orally administered to BALB/c mice every 12 h (3 times in total). After the last dose, mice were subjected to restraint stress for 6 h, and serum levels of aspartate and alanine aminotransferases, and hepatic levels of lipid peroxidation were determined. Hepatic levels of sulfur-containing metabolites such as methionine, S-adenosylmethionine, cysteine, and glutathione were also measured. The level of pro-inflammatory mediators in both liver and serum was determined. To study the mechanism of the effects of silymarin, we assessed Jun N-terminal kinase (JNK) activation and apoptotic signaling. Restraint stress induced severe oxidative stress and increased mRNA levels of pro-inflammatory mediators; both effects of restraint stress were significantly inhibited by silymarin. Moreover, administration of silymarin significantly prevented acute liver injury induced by restraint stress by blocking JNK activation and subsequently apoptotic signaling. In conclusion, these results suggest that the inhibition of restraint stress–induced liver injury by silymarin is due at least in part to its anti-oxidant activity and its ability to suppress the inflammatory response. Full article

(This article belongs to the Section Medicinal Chemistry)

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16 pages, 4697 KiB

Open AccessArticle

LC-UV Determination of Baicalin in Rabbit Plasma and Tissues for Application in Pharmacokinetics and Tissue Distribution Studies of Baicalin after Intravenous Administration of Liposomal and Injectable Formulations

by Yumeng Wei, Chao Pi, Gang Yang, Xiaoming Xiong, Yongshu Lan, Hongru Yang, Yang Zhou, Yun Ye, Yonggen Zou, Wenwu Zheng and Ling Zhao

Molecules 2016, 21(4), 444; https://doi.org/10.3390/molecules21040444 - 19 Apr 2016

Cited by 36 | Viewed by 5969

Abstract

A simple and sensitive LC-UV method to investigate the pharmacokinetics and biodistribution pattern of baicalin in rabbits was established and validated. Baicalin and the internal standard, rutin, were extracted from biosamples using acetonitrile as protein precipitation after pretreated with ammonium acetate buffer (pH [...] Read more.

A simple and sensitive LC-UV method to investigate the pharmacokinetics and biodistribution pattern of baicalin in rabbits was established and validated. Baicalin and the internal standard, rutin, were extracted from biosamples using acetonitrile as protein precipitation after pretreated with ammonium acetate buffer (pH 3.5; 1 M) to obtain a pure chromatographic peak and high extraction recovery. Chromatographic separation was achieved on a reverse-phase C18 column with a gradient elution at flow rate of 1.0 mL/min. UV absorption was set at 278 nm. Chromatographic response was linear over the ranges of 0.05–10.00 μg/mL in plasma and 0.05–300.00 μg/g in tissues with the limits of quantification of 50.0 ng/mL in plasma and tissues, and the limit of detection of baicalin in bio-samples of 15 ng/mL. The RSD of intra-and inter-day for the biosamples were from 4.19% to 10.84% and from 4.37% to 10.93%, respectively. The accuracy of plasma and tissue samples ranged from 81.6% to 95.2% and 80.8% to 98.4%, respectively. The extraction recoveries ranged from 81.5% to 88.3% for plasma, from 73.1% to 93.2% for tissues, respectively. Baicalin was stable in rabbit biosamples. The validated method was successfully applied to the study of the pharmacokinetics and tissue distribution of baicalin after intravenous administration of liposomal and injectable formulations to rabbits. Compared to baicalin injection, the pharmacokinetics and biodistribution behavior of baicalin was altered significantly in rabbits treated with its liposomes and drug concentration in the lungs was greatly increased. Full article

(This article belongs to the Section Natural Products Chemistry)

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13 pages, 224 KiB

Open AccessArticle

In Vitro Activity of Selected West African Medicinal Plants against Mycobacterium ulcerans Disease

by Patrick Valere Tsouh Fokou, Abena Adomah Kissi-Twum, Dorothy Yeboah-Manu, Regina Appiah-Opong, Phyllis Addo, Lauve Rachel Tchokouaha Yamthe, Alvine Ngoutane Mfopa, Fabrice Fekam Boyom and Alexander Kwadwo Nyarko

Molecules 2016, 21(4), 445; https://doi.org/10.3390/molecules21040445 - 13 Apr 2016

Cited by 17 | Viewed by 7284

Abstract

Buruli ulcer (BU) is the third most prevalent mycobacteriosis, after tuberculosis and leprosy. The currently recommended combination of rifampicin-streptomycin suffers from side effects and poor compliance, which leads to reliance on local herbal remedies. The objective of this study was to investigate the [...] Read more.

Buruli ulcer (BU) is the third most prevalent mycobacteriosis, after tuberculosis and leprosy. The currently recommended combination of rifampicin-streptomycin suffers from side effects and poor compliance, which leads to reliance on local herbal remedies. The objective of this study was to investigate the antimycobacterial properties and toxicity of selected medicinal plants. Sixty-five extracts from 27 plant species were screened against Mycobacterium ulcerans and Mycobacterium smegmatis, using the Resazurin Microtiter Assay (REMA). The cytotoxicity of promising extracts was assayed on normal Chang liver cells by an MTT assay. Twenty five extracts showed activity with minimal inhibitory concentration (MIC) values ranging from 16 µg/mL to 250 µg/mL against M. smegmatis, while 17 showed activity against M. ulcerans with MIC values ranging from 125 µg/mL to 250 µg/mL. In most of the cases, plant extracts with antimycobacterial activity showed no cytotoxicity on normal human liver cells. Exception were Carica papaya, Cleistopholis patens, and Polyalthia suaveolens with 50% cell cytotoxic concentrations (CC₅₀) ranging from 3.8 to 223 µg/mL. These preliminary results support the use of some West African plants in the treatment of Buruli ulcer. Meanwhile, further studies are required to isolate and characterize the active ingredients in the extracts. Full article

(This article belongs to the Collection Natural Products as Leads or Drugs against Neglected Tropical Diseases)

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8 pages, 465 KiB

Open AccessArticle

Screening for Antibacterial and Antioxidant Activities and Phytochemical Analysis of Oroxylum indicum Fruit Extracts

by Patchima Sithisarn, Petcharat Nantateerapong, Piyanuch Rojsanga and Pongtip Sithisarn

Molecules 2016, 21(4), 446; https://doi.org/10.3390/molecules21040446 - 7 Apr 2016

Cited by 28 | Viewed by 8536

Abstract

Oroxylum indicum, which is called Pheka in Thai, is a traditional Thai plant in the Bignoniaceae family with various ethnomedical uses such as as an astringent, an anti-inflammatory agent, an anti-bronchitic agent, an anti-helminthic agent and an anti-microbial agent. The young fruits [...] Read more.

Oroxylum indicum, which is called Pheka in Thai, is a traditional Thai plant in the Bignoniaceae family with various ethnomedical uses such as as an astringent, an anti-inflammatory agent, an anti-bronchitic agent, an anti-helminthic agent and an anti-microbial agent. The young fruits of this plant have also been consumed as vegetables. However, there has been no report concerning its antibacterial activities, especially activities related to clinically isolated pathogenic bacteria and the in vitro antioxidant effects of this plant. Therefore, the extracts from O. indicum fruits and seeds collected from different provinces in Thailand were prepared by decoction and maceration with ethanol and determined for their in vitro antibacterial effects on two clinically isolated bacteria, Streptococcus suis and Staphylococcus intermedius, using disc diffusion assay. Ethanol extracts from O. indicum fruits collected from Nakorn Pathom province at the concentration of 1000 mg/mL exhibited intermediate antibacterial activity against S. intermedius with an inhibition zone of 15.11 mm. Moreover, it promoted moderate inhibitory effects on S. suis with an inhibition zone of 14.39 mm. The extracts prepared by maceration with ethanol promoted higher antibacterial activities than those prepared with water. The ethanol extract from the seeds of this plant, purchased in Bangkok, showed stronger in vitro antioxidant activities than the other extracts, with an EC₅₀ value of 26.33 µg/mL. Phytochemical analysis suggested that the seed ethanol extract contained the highest total phenolic and flavonoid contents (10.66 g% gallic acid equivalent and 7.16 g% quercetin equivalent, respectively) by a significant amount. Thin layer chromatographic analysis of the extracts showed the chromatographic band that could correspond to a flavonoid baicalein. From the results, extracts from O. indicum fruits have an in vitro antioxidant effect, with antibacterial potential, on clinically pathologic bacteria and they contain an antioxidant flavonoid which could be developed for medicinal and pharmaceutical purposes in the future. 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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16 pages, 5363 KiB

Open AccessArticle

Synthesis of Dense and Chiral Dendritic Polyols Using Glyconanosynthon Scaffolds

by Tze Chieh Shiao, Rabindra Rej, Mariécka Rose, Giovanni M. Pavan and René Roy

Molecules 2016, 21(4), 448; https://doi.org/10.3390/molecules21040448 - 4 Apr 2016

Cited by 10 | Viewed by 8568

Abstract

Most classical dendrimers are frequently built-up from identical repeating units of low valency (usually AB2 monomers). This strategy necessitates several generations to achieve a large number of surface functionalities. In addition, these typical monomers are achiral. We propose herein the use of sugar [...] Read more.

Most classical dendrimers are frequently built-up from identical repeating units of low valency (usually AB2 monomers). This strategy necessitates several generations to achieve a large number of surface functionalities. In addition, these typical monomers are achiral. We propose herein the use of sugar derivatives consisting of several and varied functionalities with their own individual intrinsic chirality as both scaffolds/core as well as repeating units. This approach allows the construction of chiral, dense dendrimers with a large number of surface groups at low dendrimer generations. Perpropargylated β-D-glucopyranoside, serving as an A5 core, together with various derivatives, such as 2-azidoethyl tetra-O-allyl-β-D-glucopyranoside, serving as an AB4 repeating moiety, were utilized to construct chiral dendrimers using “click chemistry” (CuAAC reaction). These were further modified by thiol-ene and thiol-yne click reactions with alcohols to provide dendritic polyols. Molecular dynamic simulation supported the assumption that the resulting polyols have a dense structure. Full article

(This article belongs to the Special Issue Functional Dendrimers)

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11 pages, 1115 KiB

Open AccessArticle

Effects of Phenolic Acids on the Growth and Production of T‐2 and HT‐2 Toxins by Fusarium langsethiae and F. sporotrichioides

by Elena Ferruz, Vessela Atanasova‐Pénichon, Marie‐Noëlle Bonnin‐Verdal, Gisèle Marchegay, Laëtitia Pinson‐Gadais, Christine Ducos, Susana Lorán, Agustín Ariño, Christian Barreau and Florence Richard‐Forget

Molecules 2016, 21(4), 449; https://doi.org/10.3390/molecules21040449 - 4 Apr 2016

Cited by 53 | Viewed by 6889

Abstract

The effect of natural phenolic acids was tested on the growth and production of T‐2 and HT‐2 toxins by Fusarium langsethiae and F. sporotrichioides, on Mycotoxin Synthetic medium. Plates treated with 0.5 mM of each phenolic acid (caffeic, chlorogenic, ferulic and p‐coumaric) and [...] Read more.

The effect of natural phenolic acids was tested on the growth and production of T‐2 and HT‐2 toxins by Fusarium langsethiae and F. sporotrichioides, on Mycotoxin Synthetic medium. Plates treated with 0.5 mM of each phenolic acid (caffeic, chlorogenic, ferulic and p‐coumaric) and controls without phenolic acid were incubated for 14 days at 25 °C. Fungal biomass of F. langsethiae and F. sporotrichioides was not reduced by the phenolic acids. However, biosynthesis of T‐2 toxin by F. langsethiae was significantly reduced by chlorogenic (23.1%) and ferulic (26.5%) acids. Production of T‐2 by F. sporotrichioides also decreased with ferulic acid by 23% (p < 0.05). In contrast, p‐coumaric acid significantly stimulated the production of T‐2 and HT‐2 toxins for both strains. A kinetic study of F. langsethiae with 1 mM ferulic acid showed a significant decrease in fungal biomass, whereas T‐2 production increased after 10 days of incubation. The study of gene expression in ferulic supplemented cultures of F. langsethiae revealed a significant inhibition for Tri5, Tri6 and Tri12 genes, while for Tri16 the decrease in gene expression was not statistically significant. Overall, results indicated that phenolic acids had a variable effect on fungal growth and mycotoxin production, depending on the strain and the concentration and type of phenolic acid assayed. Full article

(This article belongs to the Special Issue Natural Toxins)

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10 pages, 1227 KiB

Open AccessArticle

Anti‐Inflammatory Effect of Quercetin on RAW 264.7 Mouse Macrophages Induced with Polyinosinic‐Polycytidylic Acid

by Young‐Jin Kim and Wansu Park

Molecules 2016, 21(4), 450; https://doi.org/10.3390/molecules21040450 - 4 Apr 2016

Cited by 78 | Viewed by 11335

Abstract

Quercetin (3,3′,4′,5,6‐pentahydroxyflavone) is a well‐known antioxidant and a flavonol found in many fruits, leaves, and vegetables. Quercetin also has known anti‐inflammatory effects on lipopolysaccharide‐induced macrophages. However, the effects of quercetin on virus‐induced macrophages have not been fully reported. In this study, the anti‐inflammatory [...] Read more.

Quercetin (3,3′,4′,5,6‐pentahydroxyflavone) is a well‐known antioxidant and a flavonol found in many fruits, leaves, and vegetables. Quercetin also has known anti‐inflammatory effects on lipopolysaccharide‐induced macrophages. However, the effects of quercetin on virus‐induced macrophages have not been fully reported. In this study, the anti‐inflammatory effect of quercetin on double‐stranded RNA (dsRNA)‐induced macrophages was examined. Quercetin at concentrations up to 50 μM significantly inhibited the production of NO, IL‐6, MCP‐1, IP‐10, RANTES, GM‐CSF, G‐CSF, TNF‐α, LIF, LIX, and VEGF as well as calcium release in dsRNA (50 μg/mL of polyinosinic‐polycytidylic acid)‐induced RAW 264.7 mouse macrophages (p < 0.05). Quercetin at concentrations up to 50 μM also significantly inhibited mRNA expression of signal transducer and activated transcription 1 (STAT1) and STAT3 in dsRNA‐induced RAW 264.7 cells (p < 0.05). In conclusion, quercetin had alleviating effects on viral inflammation based on inhibition of NO, cytokines, chemokines, and growth factors in dsRNA‐induced macrophages via the calcium‐STAT pathway. Full article

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

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19 pages, 5213 KiB

Open AccessArticle

Long Chain Fatty Acid Esters of Quercetin-3-O-glucoside Attenuate H₂O₂-induced Acute Cytotoxicity in Human Lung Fibroblasts and Primary Hepatocytes

by Sumudu N. Warnakulasuriya, Ziaullah and H. P. Vasantha Rupasinghe

Molecules 2016, 21(4), 452; https://doi.org/10.3390/molecules21040452 - 6 Apr 2016

Cited by 19 | Viewed by 6795

Abstract

Cellular oxidative stress causes detrimental effects to macromolecules, such as lipids, nucleic acids and proteins, leading to many pathological conditions. Quercetin-3-O-glucoside (Q3G), a glycosylated derivative of quercetin (Q), is a natural polyphenolic compound known to possess antioxidant activity. The hydrophilic/lipophilic nature [...] Read more.

Cellular oxidative stress causes detrimental effects to macromolecules, such as lipids, nucleic acids and proteins, leading to many pathological conditions. Quercetin-3-O-glucoside (Q3G), a glycosylated derivative of quercetin (Q), is a natural polyphenolic compound known to possess antioxidant activity. The hydrophilic/lipophilic nature of an antioxidant molecule is considered as an important factor governing the accessibility to the active sites of oxidative damages in vivo. Six long chain fatty acid esters of Q3G were evaluated with comparison to Q and Q3G, for their cytoprotective activity under H₂O₂-induced oxidative stress using cell culture model systems through cell viability, lipid peroxidation and fluorescence microscopy studies. Pre-incubation of α-linolenic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) esters of Q3G exhibited significantly (p ≤ 0.05) greater cell viability in both human lung fibroblast (WI-38) and human primary hepatocytes upon exposure to H₂O₂ insult when compared to the control. Cytoprotection due to oleic acid and linoleic acid esters of Q3G was observed only in human primary hepatocytes. All the derivatives, Q3G and quercetin showed ability to significantly (p ≤ 0.05) lower production of lipid hydroperoxides under induced oxidative stress, compared to the control. However, ALA and DHA esters of Q3G resulted in significantly lower lipid hydroperoxidation than Q and Q3G. Based on fluorescence microscopy study, H₂O₂-induced apoptosis was attenuated by the fatty acid derivatives of Q3G. The fatty acid derivatives of Q3G possess better cytoprotective effect than Q3G against H₂O₂-induced cytotoxicity in vitro and the concentration should be selected to avoid cytotoxicity. Full article

(This article belongs to the Section Natural Products Chemistry)

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13 pages, 2250 KiB

Open AccessArticle

Anti-Obesity and Hypoglycemic Effects of Poncirus trifoliata L. Extracts in High-Fat Diet C57BL/6 Mice

by Sheng Jia, Zhiwei Gao, Shuxia Yan, Yanhong Chen, Chongde Sun, Xian Li and Kunsong Chen

Molecules 2016, 21(4), 453; https://doi.org/10.3390/molecules21040453 - 6 Apr 2016

Cited by 24 | Viewed by 7821

Abstract

The present study investigated the possible anti-obesity and hypoglycemic effects of Poncirus trifoliata L. extracts. Mature fruit were divided into flavedo (PF) and juice sacs (PJ), and extracts from them were tested on C57BL/6 mice fed a high-fat diet (HFD) for thirteen weeks. [...] Read more.

The present study investigated the possible anti-obesity and hypoglycemic effects of Poncirus trifoliata L. extracts. Mature fruit were divided into flavedo (PF) and juice sacs (PJ), and extracts from them were tested on C57BL/6 mice fed a high-fat diet (HFD) for thirteen weeks. Both fruit extracts (40 mg/kg body weight, respectively) showed anti-obesity and hypoglycemic effects. Consumption of PF and PJ extracts reduced body weight by 9.21% and 20.27%, respectively. Liver and adipose weights, fasting glucose, serum triglyceride (TG), and low density lipoprotein cholesterol (LDL-c) levels decreased significantly, while serum high density lipoprotein cholesterol (HDL-c) and oral glucose tolerance levels increased significantly in response to two fruit extracts. These effects were due in part to the modulation of serum insulin, leptin, and adiponectin. Furthermore, transcript levels of fatty acid synthase (FAS) and stearoyl-CoA desaturase 1 (SCD1) were reduced while those of carnitine palmitoyltransferase 1α (CPT1α) and insulin receptor substrate 2 (IRS2) were increased in the liver of C57BL/6 mice, which might be an important mechanism affecting lipid and glucose metabolism. Taken together, P. trifoliata fruit can be potentially used to prevent or treat obesity and associated metabolic disorders. Full article

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

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15 pages, 1821 KiB

Open AccessArticle

Wild Bitter Melon Leaf Extract Inhibits Porphyromonas gingivalis-Induced Inflammation: Identification of Active Compounds through Bioassay-Guided Isolation

by Tzung-Hsun Tsai, Wen-Cheng Huang, How-Ting Ying, Yueh-Hsiung Kuo, Chien-Chang Shen, Yin-Ku Lin and Po-Jung Tsai

Molecules 2016, 21(4), 454; https://doi.org/10.3390/molecules21040454 - 6 Apr 2016

Cited by 26 | Viewed by 8153

Abstract

Porphyromonas gingivalis has been identified as one of the major periodontal pathogens. Activity-directed fractionation and purification processes were employed to identify the anti-inflammatory active compounds using heat-killed P. gingivalis-stimulated human monocytic THP-1 cells in vitro. Five major fractions were collected from [...] Read more.

Porphyromonas gingivalis has been identified as one of the major periodontal pathogens. Activity-directed fractionation and purification processes were employed to identify the anti-inflammatory active compounds using heat-killed P. gingivalis-stimulated human monocytic THP-1 cells in vitro. Five major fractions were collected from the ethanol/ethyl acetate extract of wild bitter melon (Momordica charantia Linn. var. abbreviata Ser.) leaves and evaluated for their anti-inflammatory activity against P. gingivalis. Among the test fractions, Fraction 5 effectively decreased heat-killed P. gingivalis-induced interleukin (IL)-8 and was subjected to separation and purification by using chromatographic techniques. Two cucurbitane triterpenoids were isolated from the active fraction and identified as 5β,19-epoxycucurbita-6,23-diene-3β,19,25-triol (1) and 3β,7β,25-trihydroxycucurbita-5,23-dien-19-al (2) by comparing spectral data. Treatments of both compounds in vitro potently suppressed P. gingivalis-induced IL-8, IL-6, and IL-1β levels and the activation of mitogen-activated protein kinase (MAPK) in THP-1 cells. Both compounds effectively inhibited the mRNA levels of IL-6, tumor necrosis factor (TNF)-α, and cyclooxygenase (COX)-2 in P. gingivalis-stimulated gingival tissue of mice. These findings imply that 5β,19-epoxycucurbita-6,23-diene-3β,19,25-triol and 3β,7β,25-trihydroxycucurbita-5,23-dien-19-al could be used for the development of novel therapeutic approaches against P. gingivalis infections. Full article

(This article belongs to the Collection Herbal Medicine Research)

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17 pages, 2183 KiB

Open AccessArticle

New Look on 3-Hydroxyiminoflavanone and Its Palladium(II) Complex: Crystallographic and Spectroscopic Studies, Theoretical Calculations and Cytotoxic Activity

by Maria Kasprzak, Małgorzata Fabijańska, Lilianna Chęcińska, Leszek Szmigiero and Justyn Ochocki

Molecules 2016, 21(4), 455; https://doi.org/10.3390/molecules21040455 - 13 Apr 2016

Cited by 5 | Viewed by 5353

Abstract

This work presents the synthesis, spectroscopic properties and single-crystal X-ray examination of the structure of 3-hydroxyiminoflavanone and its palladium complex. It presents the results of NMR (Nuclear Magnetic Resonance) spectroscopy, electron-density studies based on X-ray wavefunction refinement and theoretical calculations combined with QTAIM [...] Read more.

This work presents the synthesis, spectroscopic properties and single-crystal X-ray examination of the structure of 3-hydroxyiminoflavanone and its palladium complex. It presents the results of NMR (Nuclear Magnetic Resonance) spectroscopy, electron-density studies based on X-ray wavefunction refinement and theoretical calculations combined with QTAIM (Quantum Theory of Atoms in Molecules) and ELI-D (Electron Localizability Indicator) analyses. These offer an interesting new insight into the structures and behavior of flavanone and its complex, in solid state and in solution. The study also examines the cytotoxicity of the ligand and its complex against three human ovarian and lung cancer cell lines. Full article

(This article belongs to the Section Organometallic Chemistry)

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15 pages, 3452 KiB

Open AccessArticle

Improved Oral Bioavailability Using a Solid Self-Microemulsifying Drug Delivery System Containing a Multicomponent Mixture Extracted from Salvia miltiorrhiza

by Xiaolin Bi, Xuan Liu, Liuqing Di and Qiang Zu

Molecules 2016, 21(4), 456; https://doi.org/10.3390/molecules21040456 - 8 Apr 2016

Cited by 33 | Viewed by 7180

Abstract

The active ingredients of salvia (dried root of Salvia miltiorrhiza) include both lipophilic (e.g., tanshinone IIA, tanshinone I, cryptotanshinone and dihydrotanshinone I) and hydrophilic (e.g., danshensu and salvianolic acid B) constituents. The low oral bioavailability of these constituents may limit their efficacy. [...] Read more.

The active ingredients of salvia (dried root of Salvia miltiorrhiza) include both lipophilic (e.g., tanshinone IIA, tanshinone I, cryptotanshinone and dihydrotanshinone I) and hydrophilic (e.g., danshensu and salvianolic acid B) constituents. The low oral bioavailability of these constituents may limit their efficacy. A solid self-microemulsifying drug delivery system (S-SMEDDS) was developed to load the various active constituents of salvia into a single drug delivery system and improve their oral bioavailability. A prototype SMEDDS was designed using solubility studies and phase diagram construction, and characterized by self-emulsification performance, stability, morphology, droplet size, polydispersity index and zeta potential. Furthermore, the S-SMEDDS was prepared by dispersing liquid SMEDDS containing liposoluble extract into a solution containing aqueous extract and hydrophilic polymer, and then freeze-drying. In vitro release of tanshinone IIA, salvianolic acid B, cryptotanshinone and danshensu from the S-SMEDDS was examined, showing approximately 60%–80% of each active component was released from the S-SMEDDS in vitro within 20 min. In vivo bioavailability of these four constituents indicated that the S-SMEDDS showed superior in vivo oral absorption to a drug suspension after oral administration in rats. It can be concluded that the novel S-SMEDDS developed in this study increased the dissolution rate and improved the oral bioavailability of both lipophilic and hydrophilic constituents of salvia. Thus, the S-SMEDDS can be regarded as a promising new method by which to deliver salvia extract, and potentially other multicomponent drugs, by the oral route. Full article

(This article belongs to the Section Medicinal Chemistry)

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10 pages, 1240 KiB

Open AccessArticle

Antimicrobial Diterpenoids of Wedelia trilobata (L.) Hitchc

by Shi-Fei Li, Jia-Yin Ding, Ya-Ting Li, Xiao-Jiang Hao and Shun-Lin Li

Molecules 2016, 21(4), 457; https://doi.org/10.3390/molecules21040457 - 7 Apr 2016

Cited by 17 | Viewed by 7419

Abstract

Continued interest in the metabolites of Wedelia trilobata (L.) Hitchc, a notoriously invasive weed in South China, led to the isolation of twenty-six ent-kaurane diterpenoids, including seven new ones 1–7. Their structures and relative configuration were elucidated on the basis of extensive [...] Read more.

Continued interest in the metabolites of Wedelia trilobata (L.) Hitchc, a notoriously invasive weed in South China, led to the isolation of twenty-six ent-kaurane diterpenoids, including seven new ones 1–7. Their structures and relative configuration were elucidated on the basis of extensive spectroscopic analysis, including 1D- and 2D-NMR experiments. The antimicrobial activities of all isolated diterpenoids were evaluated against a panel of bacteria and fungi. Full article

(This article belongs to the Special Issue Diterpene and Its Significance in Natural Medicine)

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11 pages, 4626 KiB

Open AccessArticle

Formation and Transformation Behavior of Sodium Dehydroacetate Hydrates

by Xia Zhang, Chuang Xie, Yaohui Huang, Baohong Hou, Ying Bao, Junbo Gong, Qiuxiang Yin and Sohrab Rohani

Molecules 2016, 21(4), 458; https://doi.org/10.3390/molecules21040458 - 6 Apr 2016

Cited by 5 | Viewed by 7026

Abstract

The effect of various controlling factors on the polymorphic outcome of sodium dehydroacetate crystallization was investigated in this study. Cooling crystallization experiments of sodium dehydroacetate in water were conducted at different concentrations. The results revealed that the rate of supersaturation generation played a [...] Read more.

The effect of various controlling factors on the polymorphic outcome of sodium dehydroacetate crystallization was investigated in this study. Cooling crystallization experiments of sodium dehydroacetate in water were conducted at different concentrations. The results revealed that the rate of supersaturation generation played a key role in the formation of the hydrates. At a high supersaturation generation rate, a new sodium dehydroacetate dihydrate needle form was obtained; on the contrary, a sodium dehydroacetate plate monohydrate was formed at a low supersaturation generation rate. Furthermore, the characterization and transformation behavior of these two hydrated forms were investigated with the combined use of microscopy, powder X-ray diffraction (PXRD), Raman spectroscopy, Fourier transform infrared (FTIR), thermal gravimetric analysis (TGA), scanning electron microscopy (SEM) and dynamic vapor sorption (DVS). It was found that the new needle crystals were dihydrated and hollow, and they eventually transformed into sodium dehydroacetate monohydrate. In addition, the mechanism of formation of sodium dehydroacetate hydrates was discussed, and a process growth model of hollow crystals in cooling crystallization was proposed. Full article

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

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9 pages, 909 KiB

Open AccessArticle

Inhibition of Nitric Oxide Production in BV2 Microglial Cells by Triterpenes from Tetrapanax papyriferus

by Namki Cho, Eun Hye Moon, Hyun Woo Kim, Jaewoo Hong, John A. Beutler and Sang Hyun Sung

Molecules 2016, 21(4), 459; https://doi.org/10.3390/molecules21040459 - 7 Apr 2016

Cited by 22 | Viewed by 7468

Abstract

It is well known that activated microglia produce nitric oxide (NO), which has an important role in the pathophysiology of several neurodegenerative diseases such as Alzheimer’s disease. In the course of searching for novel therapeutic agents from medicinal plants against neuroinflammatory diseases, the [...] Read more.

It is well known that activated microglia produce nitric oxide (NO), which has an important role in the pathophysiology of several neurodegenerative diseases such as Alzheimer’s disease. In the course of searching for novel therapeutic agents from medicinal plants against neuroinflammatory diseases, the methanolic extract of Tetrapanax papyriferus was found to have significant NO inhibitory activity in lipopolysaccharide (LPS)-stimulated BV2 microglia cells. Nine oleanane-type triterpenes, including two new compounds, epipapyriogenin C-3-O-β-d-glucopyranoside (6) and 11-O-butylpapyrioside LIIc (9), were isolated from the leaves and stems of Tetrapanax papyriferus. The structures of these compounds were elucidated with 1D- and 2D-NMR and MS data. Among these Δ^11,13 oleanane-type triterpenes, compound 3 showed significant NO inhibitory activity in BV-2 cells, reducing the LPS-induced expression of COX-2 and pro-inflammatory cytokines such as TNF-α and IL-6. Compounds 7 and 9 also showed NO inhibitory activities among the Δ¹² oleanane-type triterpene saponins. These results show that oleanane-type triterpenes isolated from T. papyriferus could be a potential natural resource of NO inhibitors used in the treatment of neurodegenerative disorders. Full article

(This article belongs to the Collection Triterpenes and Triterpenoids)

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11 pages, 4072 KiB

Open AccessArticle

The Apoptotic Effect of Ursolic Acid on SK-Hep-1 Cells is Regulated by the PI3K/Akt, p38 and JNK MAPK Signaling Pathways

by Wan-Ling Chuang, Ping-Yi Lin, Hui-Chuan Lin and Yao-Li Chen

Molecules 2016, 21(4), 460; https://doi.org/10.3390/molecules21040460 - 20 Apr 2016

Cited by 33 | Viewed by 6834

Abstract

Ursolic acid (UA) is a pentacyclic triterpene acid that is present in a wide variety of medicinal herbs and edible plants. This study investigated the effect of UA on apoptosis and proliferation of hepatocellular carcinoma SK-Hep-1 cells. After treatment of SK-Hep-1 cells with [...] Read more.

Ursolic acid (UA) is a pentacyclic triterpene acid that is present in a wide variety of medicinal herbs and edible plants. This study investigated the effect of UA on apoptosis and proliferation of hepatocellular carcinoma SK-Hep-1 cells. After treatment of SK-Hep-1 cells with different concentrations of UA, we observed that cell viability was reduced in a dose- and time-dependent manner. Furthermore, there was a dose-dependent increase in the percentage of cells in the sub-G1 and G2/M phases, with cells treated with 60 μM showing the highest percentages of cells in those phases. UA-induced chromatin condensation of nuclei was observed by using DAPI staining. The western blot results revealed that exposure to UA was associated with decreased expression of the anti-apoptotic proteins Mcl-1, Bcl-xL, Bcl-2, and TCTP and increased expression of apoptosis-related proteins TNF-α, Fas, FADD, Bax, cleaved caspase-3, caspase-8, caspase-9, and PARP. Immunocytochemistry staining showed that treatment with UA resulted in increased expression of caspase-3. Moreover, exposure to UA resulted in the inhibition of the PI3K/Akt and p38 MAPK signaling pathways. These findings suggest that UA inhibits the proliferation of SK-Hep-1 cells and induces apoptosis. Full article

(This article belongs to the Section Natural Products Chemistry)

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13 pages, 5728 KiB

Open AccessArticle

Effects of Phlomis umbrosa Root on Longitudinal Bone Growth Rate in Adolescent Female Rats

by Donghun Lee, Young-Sik Kim, Jungbin Song, Hyun Soo Kim, Hyun Jung Lee, Hailing Guo and Hocheol Kim

Molecules 2016, 21(4), 461; https://doi.org/10.3390/molecules21040461 - 7 Apr 2016

Cited by 30 | Viewed by 9739

Abstract

This study aimed to investigate the effects of Phlomis umbrosa root on bone growth and growth mediators in rats. Female adolescent rats were administered P. umbrosa extract, recombinant human growth hormone or vehicle for 10 days. Tetracycline was injected intraperitoneally to produce a [...] Read more.

This study aimed to investigate the effects of Phlomis umbrosa root on bone growth and growth mediators in rats. Female adolescent rats were administered P. umbrosa extract, recombinant human growth hormone or vehicle for 10 days. Tetracycline was injected intraperitoneally to produce a glowing fluorescence band on the newly formed bone on day 8, and 5-bromo-2′-deoxyuridine was injected to label proliferating chondrocytes on days 8–10. To assess possible endocrine or autocrine/paracrine mechanisms, we evaluated insulin-like growth factor-1 (IGF-1), insulin-like growth factor binding protein-3 (IGFBP-3) or bone morphogenetic protein-2 (BMP-2) in response to P. umbrosa administration in either growth plate or serum. Oral administration of P. umbrosa significantly increased longitudinal bone growth rate, height of hypertrophic zone and chondrocyte proliferation of the proximal tibial growth plate. P. umbrosa also increased serum IGFBP-3 levels and upregulated the expressions of IGF-1 and BMP-2 in growth plate. In conclusion, P. umbrosa increases longitudinal bone growth rate by stimulating proliferation and hypertrophy of chondrocyte with the increment of circulating IGFBP-3. Regarding the immunohistochemical study, the effect of P. umbrosa may also be attributable to upregulation of local IGF-1 and BMP-2 expressions in the growth plate, which can be considered as a GH dependent autocrine/paracrine pathway. Full article

(This article belongs to the Section Natural Products Chemistry)

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8 pages, 495 KiB

Open AccessArticle

New Efficient Synthesis of 3,4-Dihydropyrimidin-2(1H)-ones Catalyzed by Benzotriazolium-Based Ionic Liquids under Solvent-Free Conditions

by Zhiqing Liu, Rong Ma, Dawei Cao and Chenjiang Liu

Molecules 2016, 21(4), 462; https://doi.org/10.3390/molecules21040462 - 7 Apr 2016

Cited by 29 | Viewed by 6385

Abstract

An efficient synthesis of novel 3,4-dihydropyrimidin-2(1H)-ones (DHPMs) and their derivatives, using Brønsted acidic ionic liquid [C₂O₂BBTA][TFA] as a catalyst, from the condensation of aryl aldehyde, β-ketoester and urea was described. Reactions proceeded smoothly for 40 min under [...] Read more.

An efficient synthesis of novel 3,4-dihydropyrimidin-2(1H)-ones (DHPMs) and their derivatives, using Brønsted acidic ionic liquid [C₂O₂BBTA][TFA] as a catalyst, from the condensation of aryl aldehyde, β-ketoester and urea was described. Reactions proceeded smoothly for 40 min under solvent-free conditions and gave the desirable products with good to excellent yields (up to 99%). The catalyst could be easily recycled and reused with similar eﬃcacies for at least six cycles. Full article

(This article belongs to the Special Issue Organic Reaction in Green Solvents)

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21 pages, 3516 KiB

Open AccessArticle

Formation of Peptide Bound Pyrraline in the Maillard Model Systems with Different Lys-Containing Dipeptides and Tripeptides

by Zhili Liang, Lin Li, Haiping Qi, Liting Wan, Panfu Cai, Zhenbo Xu and Bing Li

Molecules 2016, 21(4), 463; https://doi.org/10.3390/molecules21040463 - 7 Apr 2016

Cited by 16 | Viewed by 6765

Abstract

Peptide-bound advanced glycation end-products (peptide-bound AGEs) can be formed when peptides are heated with reducing saccharides. Pyrraline is the one of most commonly studied AGEs in foods, but the relative importance of the precursor peptide structure is uncertain. In the present study, model [...] Read more.

Peptide-bound advanced glycation end-products (peptide-bound AGEs) can be formed when peptides are heated with reducing saccharides. Pyrraline is the one of most commonly studied AGEs in foods, but the relative importance of the precursor peptide structure is uncertain. In the present study, model systems were prepared by heating peptides with glucose from 60 °C to 220 °C for up to 65 min, and the amounts of peptide-bound pyrraline formed were monitored to evaluate the effect of the neighboring amino acids on the peptide-bound pyrraline formation. The physico-chemical properties were introduced to explore the quantitative structure-reactivity relationships between physicochemical properties and peptide bound formation. 3-DG content in dipeptide-glucose model system was higher than that in the corresponding tripeptide-glucose model systems. Dipeptides produced higher amounts of peptide-bound pyrraline than the corresponding tripeptides. The peptide-bound pyrraline and 3-DG production were influenced by the physico-chemical properties of the side chain of amino acids adjacent to Lys in the following order: Lys-Leu/glucose > Lys-Ile/glucose > Lys-Val/ glucose > Lys-Thr/glucose > Lys-Ser/glucose > Lys-Ala/ glucose > Lys-Gly/glucose; Lys-Leu-Gly/glucose > Lys-Ile-Gly/glucose > Lys-Val-Gly/glucose > Lys-Thr-Gly/glucose > Lys-Ser-Gly/glucose > Lys-Ala-Gly/glucose > Lys-Gly-Gly/glucose. For the side chain of amino acids adjacent to Lys in dipeptides, residue volume, polarizability, molecular volume and localized electrical effect were positively related to the yield of peptide bound pyrraline, while hydrophobicity and pK_b were negatively related to the yield of peptide bound pyrraline. In terms of side chain of amino acid adjacent to Lys in tripeptides, a similar result was observed, except hydrophobicity was positively related to the yield of peptide bound pyrraline. Full article

(This article belongs to the Section Molecular Diversity)

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12 pages, 849 KiB

Open AccessArticle

In Vivo and in Vitro Study on Drug-Drug Interaction of Lovastatin and Berberine from Pharmacokinetic and HepG2 Cell Metabolism Studies

by Hanming Cui, Jialong Wang, Qiuyan Zhang, Mengmeng Dang, Hui Liu, Yu Dong, Lu Zhang, Fang Yang, Jianhua Wu and Xiaolin Tong

Molecules 2016, 21(4), 464; https://doi.org/10.3390/molecules21040464 - 8 Apr 2016

Cited by 20 | Viewed by 7632

Abstract

Background: We assumed that the pharmacokinetics of lovastatin could be changed by the induction effect of berberine. Methods: An UPLC-MS/MS method was developed and validated for the pharmacokinetics tudy of lovastatin to investigate the in vivo drug-drug interactions between lovastatin and [...] Read more.

Background: We assumed that the pharmacokinetics of lovastatin could be changed by the induction effect of berberine. Methods: An UPLC-MS/MS method was developed and validated for the pharmacokinetics tudy of lovastatin to investigate the in vivo drug-drug interactions between lovastatin and berberine. SD male rats were random divided into lovastatin group and berberine induced prior to lovastatin group for the in vivo pharmacokinetic studies. Meanwhile HepG2 cells were induced by berberine for three days to study the metabolism of lovastatin. Results: The AUC (p < 0.01) and C_max (p < 0.01) could be significantly decreased in the berberine-induced group in vivo, and the metabolic activity of HepG2 cell ccould be increased by berberine induction in vitro. The metabolism parameters of lovastatin such as CL, V_max and K_m were increased after the induction of berberine. From the pharmacokinetic study of lovastatin induced with berberine, we obtained pharmacokinetic parameters which are compliance with the metabolic parameters of lovastatin in HepG2 cells with berberine induction in vitro. Conclusions: From the in vivo pharmacokinetics study and the HepG2 cell metabolism study in vitro, berberine could be an inducer for the metabolism of lovastatin according to our previous research on berberine induction effects on HepG2 cells, which may be relevant to the fact that berberine possesses induction effects through the CYP 450 3A4 enzyme. Full article

(This article belongs to the Section Metabolites)

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13 pages, 1973 KiB

Open AccessArticle

by Joseph Schwager, Nathalie Richard, Ann Fowler, Nicole Seifert and Daniel Raederstorff

Molecules 2016, 21(4), 465; https://doi.org/10.3390/molecules21040465 - 8 Apr 2016

Cited by 53 | Viewed by 8330

Abstract

Phenolic diterpenes present in Rosmarinus officinalis and Salvia officinalis have anti-inflammatory and chemoprotective effects. We investigated the in vitro effects of carnosol (CL), carnosic acid (CA), carnosic acid-12-methylether (CAME), 20-deoxocarnosol and abieta-8,11,13-triene-11,12,20-triol (ABTT) in murine macrophages (RAW264.7 cells) and human chondrocytes. The substances [...] Read more.

Phenolic diterpenes present in Rosmarinus officinalis and Salvia officinalis have anti-inflammatory and chemoprotective effects. We investigated the in vitro effects of carnosol (CL), carnosic acid (CA), carnosic acid-12-methylether (CAME), 20-deoxocarnosol and abieta-8,11,13-triene-11,12,20-triol (ABTT) in murine macrophages (RAW264.7 cells) and human chondrocytes. The substances concentration-dependently reduced nitric oxide (NO) and prostaglandin E₂ (PGE₂) production in LPS-stimulated macrophages (i.e., acute inflammation). They significantly blunted gene expression levels of iNOS, cytokines/interleukins (IL-1α, IL-6) and chemokines including CCL5/RANTES, CXCL10/IP-10. The substances modulated the expression of catabolic and anabolic genes in chondrosarcoma cell line SW1353 and in primary human chondrocytes that were stimulated by IL-1β (i.e., chronic inflammation In SW1353, catabolic genes like MMP-13 and ADAMTS-4 that contribute to cartilage erosion were down-regulated, while expression of anabolic genes including Col2A1 and aggrecan were shifted towards pre-pathophysiological homeostasis. CL had the strongest overall effect on inflammatory mediators, as well as on macrophage and chondrocyte gene expression. Conversely, CAME mainly affected catabolic gene expression, whereas ABTT had a more selectively altered interleukin and chemokine gene exprssion. CL inhibited the IL-1β induced nuclear translocation of NF-κBp65, suggesting that it primarily regulated via the NF-κB signalling pathway. Collectively, CL had the strongest effects on inflammatory mediators and chondrocyte gene expression. The data show that the phenolic diterpenes altered activity pattern of genes that regulate acute and chronic inflammatory processes. Since the substances affected catabolic and anabolic gene expression in cartilage cells in vitro, they may beneficially act on the aetiology of osteoarthritis. Full article

(This article belongs to the Section Natural Products Chemistry)

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13 pages, 578 KiB

Open AccessArticle

Quality Control of Gamma Irradiated Dwarf Mallow (Malva neglecta Wallr.) Based on Color, Organic Acids, Total Phenolics and Antioxidant Parameters

by José Pinela, Lillian Barros, Amilcar L. Antonio, Ana Maria Carvalho, M. Beatriz P. P. Oliveira and Isabel C. F. R. Ferreira

Molecules 2016, 21(4), 467; https://doi.org/10.3390/molecules21040467 - 8 Apr 2016

Cited by 12 | Viewed by 7575

Abstract

This study addresses the effects of gamma irradiation (1, 5 and 8 kGy) on color, organic acids, total phenolics, total flavonoids, and antioxidant activity of dwarf mallow (Malva neglecta Wallr.). Organic acids were analyzed by ultra fast liquid chromatography (UFLC) coupled to [...] Read more.

This study addresses the effects of gamma irradiation (1, 5 and 8 kGy) on color, organic acids, total phenolics, total flavonoids, and antioxidant activity of dwarf mallow (Malva neglecta Wallr.). Organic acids were analyzed by ultra fast liquid chromatography (UFLC) coupled to a photodiode array (PDA) detector. Total phenolics and flavonoids were measured by the Folin-Ciocalteu and aluminium chloride colorimetric methods, respectively. The antioxidant activity was evaluated based on the DPPH^• scavenging activity, reducing power, β-carotene bleaching inhibition and thiobarbituric acid reactive substances (TBARS) formation inhibition. Analyses were performed in the non-irradiated and irradiated plant material, as well as in decoctions obtained from the same samples. The total amounts of organic acids and phenolics recorded in decocted extracts were always higher than those found in the plant material or hydromethanolic extracts, respectively. The DPPH^• scavenging activity and reducing power were also higher in decocted extracts. The assayed irradiation doses affected differently the organic acids profile. The levels of total phenolics and flavonoids were lower in the hydromethanolic extracts prepared from samples irradiated at 1 kGy (dose that induced color changes) and in decocted extracts prepared from those irradiated at 8 kGy. The last samples also showed a lower antioxidant activity. In turn, irradiation at 5 kGy favored the amounts of total phenolics and flavonoids. Overall, this study contributes to the understanding of the effects of irradiation in indicators of dwarf mallow quality, and highlighted the decoctions for its antioxidant properties. Full article

(This article belongs to the Collection Bioactive Compounds)

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13 pages, 1611 KiB

Open AccessArticle

New Insights into the Antibacterial Activity of Hydroxycoumarins against Ralstonia solanacearum

by Liang Yang, Wei Ding, Yuquan Xu, Dousheng Wu, Shili Li, Juanni Chen and Bing Guo

Molecules 2016, 21(4), 468; https://doi.org/10.3390/molecules21040468 - 8 Apr 2016

Cited by 135 | Viewed by 10079

Abstract

Coumarins are important plant-derived natural products with wide-ranging bioactivities and extensive applications. In this study, we evaluated for the first time the antibacterial activity and mechanisms of action of coumarins against the phytopathogen Ralstonia solanacearum, and investigated the effect of functional group [...] Read more.

Coumarins are important plant-derived natural products with wide-ranging bioactivities and extensive applications. In this study, we evaluated for the first time the antibacterial activity and mechanisms of action of coumarins against the phytopathogen Ralstonia solanacearum, and investigated the effect of functional group substitution. We first tested the antibacterial activity of 18 plant-derived coumarins with different substitution patterns, and found that daphnetin, esculetin, xanthotol, and umbelliferone significantly inhibited the growth of R. solanacearum. Daphnetin showed the strongest antibacterial activity, followed by esculetin and umbelliferone, with MICs of 64, 192, and 256 mg/L, respectively, better than the archetypal coumarin with 384 mg/L. We further demonstrated that the hydroxylation of coumarins at the C-6, C-7 or C-8 position significantly enhanced the antibacterial activity against R. solanacearum. Transmission electron microscope (TEM) and fluorescence microscopy images showed that hydroxycoumarins may interact with the pathogen by mechanically destroying the cell membrane and inhibiting biofilm formation. The antibiofilm effect of hydroxycoumarins may relate to the repression of flagellar genes fliA and flhC. These physiological changes in R. solanacearum caused by hydroxycoumarins can provide information for integral pathogen control. The present findings demonstrated that hydroxycoumarins have superior antibacterial activity against the phytopathogen R. solanacearum, and thus have the potential to be applied for controlling plant bacterial wilt. Full article

(This article belongs to the Section Natural Products Chemistry)

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10 pages, 1777 KiB

Open AccessArticle

Inhibition of Listeria monocytogenes in Fresh Cheese Using Chitosan-Grafted Lactic Acid Packaging

by Laura N. Sandoval, Monserrat López, Elizabeth Montes-Díaz, Andres Espadín, Alberto Tecante, Miquel Gimeno and Keiko Shirai

Molecules 2016, 21(4), 469; https://doi.org/10.3390/molecules21040469 - 8 Apr 2016

Cited by 13 | Viewed by 6607

Abstract

A chitosan from biologically obtained chitin was successfully grafted with d,l-lactic acid (LA) in aqueous media using p-toluenesulfonic acid as catalyst to obtain a non-toxic, biodegradable packaging material that was characterized using scanning electron microscopy, water vapor permeability, and [...] Read more.

A chitosan from biologically obtained chitin was successfully grafted with d,l-lactic acid (LA) in aqueous media using p-toluenesulfonic acid as catalyst to obtain a non-toxic, biodegradable packaging material that was characterized using scanning electron microscopy, water vapor permeability, and relative humidity (RH) losses. Additionally, the grafting in chitosan with LA produced films with improved mechanical properties. This material successfully extended the shelf life of fresh cheese and inhibited the growth of Listeria monocytogenes during 14 days at 4 °C and 22% RH, whereby inoculated samples with chitosan-g-LA packaging presented full bacterial inhibition. The results were compared to control samples and commercial low-density polyethylene packaging. Full article

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

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13 pages, 2022 KiB

Open AccessArticle

Identification of 3′,4′-Dimethoxy Flavonol-3-β-d-Glucopyranoside Metabolites in Rats by Liquid Chromatography-Electrospray Ionization Ion Trap Mass Spectrometry

by Yuan Zhu, Jun Wen, Yuqing Cao, Yuanying Jiang, Jinghua Huang, Guorong Fan and Yuefen Lou

Molecules 2016, 21(4), 470; https://doi.org/10.3390/molecules21040470 - 9 Apr 2016

Cited by 4 | Viewed by 5498

Abstract

A method using liquid chromatography-electrospray ionization ion trap mass spectrometry was established for the identification of metabolites in feces, urine and bile in rats after oral administration of 3′,4′-dimethoxy flavonol-3-β-d-glucopyranoside (abbreviated DF3G). Seven metabolites in rat feces, urine and bile were [...] Read more.

A method using liquid chromatography-electrospray ionization ion trap mass spectrometry was established for the identification of metabolites in feces, urine and bile in rats after oral administration of 3′,4′-dimethoxy flavonol-3-β-d-glucopyranoside (abbreviated DF3G). Seven metabolites in rat feces, urine and bile were firstly identified on the basis of their MS fragmentation behaviors. Three metabolites were identified in the feces, 6 in the urine and 2 in the bile, which suggested that demethylation, deglycosylation and deglycosylation followed by glucuronide conjugation were the major metabolic pathways for DF3G in vivo. Hydrolyzation might be the first step in the absorption and metabolism of DF3G. The possible metabolic pathway was proposed for the first time. The established method was simple, reliable and sensitive, revealing that it could be used to rapidly screen and identify the structures of metabolites of DF3G to better understand its metabolism in vivo. Full article

(This article belongs to the Section Metabolites)

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14 pages, 1049 KiB

Open AccessArticle

Aberrant Expression of Bacterial Pattern Recognition Receptor NOD2 of Basophils and Microbicidal Peptides in Atopic Dermatitis

by Chun-Kwok Wong, Ida Miu-Ting Chu, Kam-Lun Hon, Miranda Sin-Man Tsang and Christopher Wai-Kei Lam

Molecules 2016, 21(4), 471; https://doi.org/10.3390/molecules21040471 - 11 Apr 2016

Cited by 18 | Viewed by 7157

Abstract

Atopic dermatitis (AD) is a chronically relapsing inflammatory skin disease, associated with basophil infiltration into skin lesions and Staphylococcus aureus (S. aureus)-induced inflammation. Pattern recognition receptors (PRRs), including microbicidal peptide human neutrophil α-defensins (HNP) and dermcidin, can exert immunomodulating activity in [...] Read more.

Atopic dermatitis (AD) is a chronically relapsing inflammatory skin disease, associated with basophil infiltration into skin lesions and Staphylococcus aureus (S. aureus)-induced inflammation. Pattern recognition receptors (PRRs), including microbicidal peptide human neutrophil α-defensins (HNP) and dermcidin, can exert immunomodulating activity in innate immunity and skin inflammation. We investigated the plasma concentration of HNP and dermcidin, the expression of bacterial toll-like receptor (TLR) and nucleotide-binding oligomerization domain (NOD)-like receptors of basophils and plasma concentration and ex vivo induction of AD-related inflammatory cytokines and chemokines using ELISA and flow cytometry, in AD patients and control subjects. Plasma concentrations of HNP, dermcidin and AD-related Th2 chemokines CCL17, CCL22 and CCL27 were significantly elevated in AD patients compared with controls (all p < 0.05). Plasma concentrations of CCL27 and CCL22 were found to correlate positively with SCORing atopic dermatitis (SCORAD), objective SCORAD, % area affected, lichenification and disease intensity, and CCL27 also correlated positively with pruritus in AD patients (all p < 0.05). Protein expressions of NOD2 but not TLR2 of basophils were significantly down-regulated in AD patients compared with controls (p = 0.001). Correspondingly, there were lower ex vivo % inductions of allergic inflammatory tumor necrosis factor-α, IL-6 and CXCL8 from peripheral blood mononuclear cells upon NOD2 ligand S. aureus derived muramyl dipeptide stimulation in AD patients comparing with controls. The aberrant activation of bacterial PRRs of basophils and anti-bacterial innate immune response should be related with the allergic inflammation of AD. Full article

(This article belongs to the Special Issue Molecules Mediating Allergic and Autoimmune Inflammation: Commemorative Issue in Honor of Professor Christopher W. K. Lam’s Research Achievements on the Occasion of His 70th Birthday)

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17 pages, 2089 KiB

Open AccessArticle

The Application of Vibrational Spectroscopy Techniques in the Qualitative Assessment of Material Traded as Ginseng

by Maxleene Sandasi, Ilze Vermaak, Weiyang Chen and Alvaro Viljoen

Molecules 2016, 21(4), 472; https://doi.org/10.3390/molecules21040472 - 12 Apr 2016

Cited by 14 | Viewed by 6563

Abstract

The name “ginseng” is collectively used to describe several plant species, including Panax ginseng (Asian/Oriental ginseng), P. quinquefolius (American ginseng), P. pseudoginseng (Pseudoginseng) and Eleutherococcus senticosus (Siberian ginseng), each with different applications in traditional medicine practices. The use of a generic name may [...] Read more.

The name “ginseng” is collectively used to describe several plant species, including Panax ginseng (Asian/Oriental ginseng), P. quinquefolius (American ginseng), P. pseudoginseng (Pseudoginseng) and Eleutherococcus senticosus (Siberian ginseng), each with different applications in traditional medicine practices. The use of a generic name may lead to the interchangeable use or substitution of raw materials which poses quality control challenges. Quality control methods such as vibrational spectroscopy-based techniques are here proposed as fast, non-destructive methods for the distinction of four ginseng species and the identification of raw materials in commercial ginseng products. Certified ginseng reference material and commercial products were analysed using hyperspectral imaging (HSI), mid-infrared (MIR) and near-infrared (NIR) spectroscopy. Principal component analysis (PCA) and (orthogonal) partial least squares discriminant analysis models (OPLS-DA) were developed using multivariate analysis software. UHPLC-MS was used to analyse methanol extracts of the reference raw materials and commercial products. The holistic analysis of ginseng raw materials revealed distinct chemical differences using HSI, MIR and NIR. For all methods, Eleutherococcus senticosus displayed the greatest variation from the three Panax species that displayed closer chemical similarity. Good discrimination models with high R²X and Q² cum vales were developed. These models predicted that the majority of products contained either /P. ginseng or P. quinquefolius. Vibrational spectroscopy and HSI techniques in tandem with multivariate data analysis tools provide useful alternative methods in the authentication of ginseng raw materials and commercial products in a fast, easy, cost-effective and non-destructive manner. Full article

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

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13 pages, 1712 KiB

Open AccessArticle

Eremophilane Sesquiterpenes from a Deep Marine-Derived Fungus, Aspergillus sp. SCSIOW2, Cultivated in the Presence of Epigenetic Modifying Agents

by Liyan Wang, Mengjie Li, Jianqiang Tang and Xiaofan Li

Molecules 2016, 21(4), 473; https://doi.org/10.3390/molecules21040473 - 18 Apr 2016

Cited by 48 | Viewed by 6249

Abstract

Chemical epigenetic manipulation was applied to a deep marine-derived fungus, Aspergillus sp. SCSIOW2, resulting in significant changes of the secondary metabolites. Three new eremophilane-type sesquiterpenes, dihydrobipolaroxin B (2), dihydrobipolaroxin C (3), and dihydrobipolaroxin D (4), along with one known analogue, dihydrobipolaroxin (1), were [...] Read more.

Chemical epigenetic manipulation was applied to a deep marine-derived fungus, Aspergillus sp. SCSIOW2, resulting in significant changes of the secondary metabolites. Three new eremophilane-type sesquiterpenes, dihydrobipolaroxin B (2), dihydrobipolaroxin C (3), and dihydrobipolaroxin D (4), along with one known analogue, dihydrobipolaroxin (1), were isolated from the culture treated with a combination of histone deacetylase inhibitor (suberohydroxamic acid) and DNA methyltransferase inhibitor (5-azacytidine). 1–4 were not produced in the untreated cultures. 2 and 3 might be artificial because 1 could form 2 and 3 spontaneously in water by intracellular acetalization reaction. The absolute configurations of 1 and 2 were assigned based on ECD spectroscopy combined with time-dependent density functional theory calculations. All four compounds exhibited moderate nitric oxide inhibitory activities without cytotoxic effects. Full article

(This article belongs to the Section Natural Products Chemistry)

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12 pages, 2429 KiB

Open AccessArticle

The Powdering Process with a Set of Ceramic Mills for Green Tea Promoted Catechin Extraction and the ROS Inhibition Effect

by Kouki Fujioka, Takeo Iwamoto, Hidekazu Shima, Keiko Tomaru, Hideki Saito, Masaki Ohtsuka, Akihiro Yoshidome, Yuri Kawamura and Yoshinobu Manome

Molecules 2016, 21(4), 474; https://doi.org/10.3390/molecules21040474 - 11 Apr 2016

Cited by 37 | Viewed by 17528

Abstract

For serving green tea, there are two prominent methods: steeping the leaf or the powdered leaf (matcha style) in hot water. The purpose of the present study was to reveal chemical and functional differences before and after the powdering process of green tea [...] Read more.

For serving green tea, there are two prominent methods: steeping the leaf or the powdered leaf (matcha style) in hot water. The purpose of the present study was to reveal chemical and functional differences before and after the powdering process of green tea leaf, since powdered green tea may contribute to expanding the functionality because of the different ingesting style. In this study, we revealed that the powdering process with a ceramic mill and stirring in hot water increased the average extracted concentration of epigallocatechin gallate (EGCG) by more than three times compared with that in leaf tea using high-performance liquid chromatography (HPLC) and liquid chromatography–tandem mass Spectrometry (LC-MS/MS) analyses. Moreover, powdered green tea has a higher inhibition effect of reactive oxygen species (ROS) production in vitro compared with the same amount of leaf tea. Our data suggest that powdered green tea might have a different function from leaf tea due to the higher catechin contents and particles. Full article

(This article belongs to the Special Issue New Frontiers on the Metabolism, Bioavailability and Health Effects of Phenolic Compounds)

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13 pages, 1136 KiB

Open AccessArticle

Adapting Document Similarity Measures for Ligand-Based Virtual Screening

by Mubarak Himmat, Naomie Salim, Mohammed Mumtaz Al-Dabbagh, Faisal Saeed and Ali Ahmed

Molecules 2016, 21(4), 476; https://doi.org/10.3390/molecules21040476 - 13 Apr 2016

Cited by 22 | Viewed by 5517

Abstract

Quantifying the similarity of molecules is considered one of the major tasks in virtual screening. There are many similarity measures that have been proposed for this purpose, some of which have been derived from document and text retrieving areas as most often these [...] Read more.

Quantifying the similarity of molecules is considered one of the major tasks in virtual screening. There are many similarity measures that have been proposed for this purpose, some of which have been derived from document and text retrieving areas as most often these similarity methods give good results in document retrieval and can achieve good results in virtual screening. In this work, we propose a similarity measure for ligand-based virtual screening, which has been derived from a text processing similarity measure. It has been adopted to be suitable for virtual screening; we called this proposed measure the Adapted Similarity Measure of Text Processing (ASMTP). For evaluating and testing the proposed ASMTP we conducted several experiments on two different benchmark datasets: the Maximum Unbiased Validation (MUV) and the MDL Drug Data Report (MDDR). The experiments have been conducted by choosing 10 reference structures from each class randomly as queries and evaluate them in the recall of cut-offs at 1% and 5%. The overall obtained results are compared with some similarity methods including the Tanimoto coefficient, which are considered to be the conventional and standard similarity coefficients for fingerprint-based similarity calculations. The achieved results show that the performance of ligand-based virtual screening is better and outperforms the Tanimoto coefficients and other methods. Full article

(This article belongs to the Section Molecular Diversity)

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10 pages, 986 KiB

Open AccessArticle

Green Technique-Solvent Free Microwave Synthesis and Antimicrobial Evaluation of New Thiopyridine Arabinosides

by Ibrahim A. Maghrabi, Saleh Alghamdi, Majed Alrobaian and Hany A. Eldeab

Molecules 2016, 21(4), 477; https://doi.org/10.3390/molecules21040477 - 19 Apr 2016

Cited by 9 | Viewed by 5172

Abstract

A green protocol has been applied to synthesize a novel series of 3-cyano-2-(tri-O-acetyl-β-d-arabinopyranosylthio)pyridines in a short reaction time, in higher yields and with simpler operations, when compared with the conventional heating method. Deacetylation of the obtained acetylated arabinosides produced [...] Read more.

A green protocol has been applied to synthesize a novel series of 3-cyano-2-(tri-O-acetyl-β-d-arabinopyranosylthio)pyridines in a short reaction time, in higher yields and with simpler operations, when compared with the conventional heating method. Deacetylation of the obtained acetylated arabinosides produced 2-(β-d-arabinopyranosylthio)-3-cyanopyridines. The structures of the obtained products were confirmed on the basis of spectroscopic data (FT-IR, 1D, 2D-NMR). The synthesized compounds were screened for the antimicrobial activity against a selection of Gram positive and Gram negative bacteria. Full article

(This article belongs to the Special Issue Organic Reaction in Green Solvents)

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11 pages, 2228 KiB

Open AccessArticle

Highly Efficient Synthesis of an Emerging Lipophilic Antioxidant: 2-Ethylhexyl Ferulate

by Kuo-Chuan Huang, Ying Li, Chia-Hung Kuo, Yawo-Kuo Twu and Chwen-Jen Shieh

Molecules 2016, 21(4), 478; https://doi.org/10.3390/molecules21040478 - 12 Apr 2016

Cited by 20 | Viewed by 5450

Abstract

Ferulic acid in ester form has shown a stronger ability in ameliorating certain pathological conditions and inhibiting lipid oxidation. In present study, a solvent-free and reduced pressure evaporation system was developed for lipase-catalyzed synthesis of 2-ethylhexyl ferulate (2-EF) from ferulic acid and 2-ethylhexanol. [...] Read more.

Ferulic acid in ester form has shown a stronger ability in ameliorating certain pathological conditions and inhibiting lipid oxidation. In present study, a solvent-free and reduced pressure evaporation system was developed for lipase-catalyzed synthesis of 2-ethylhexyl ferulate (2-EF) from ferulic acid and 2-ethylhexanol. A Box-Behnken design with response surface methodology (RSM) and artificial neural network (ANN) was selected to model and optimize the process. Based on the yields of 2-EF, reaction temperature was shown to be the most important process factor on the molar conversion among all variables. The residual values and the coefficient of determination (R²) calculated from the design data indicated that ANN was better than RSM in data fitting. Overall, the present lipase-catalyzed approach for 2-EF synthesis at low reaction temperature in a reduced pressure evaporation system shows high 2-EF production efficiency. Notably, this approach can reduce the enzyme denaturation and ferulic acid oxidation that usually occur during long-term biosynthetic operations at high temperature. Full article

(This article belongs to the Section Green Chemistry)

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10 pages, 1299 KiB

Open AccessArticle

Phenolic Constituents of Medicinal Plants with Activity against Trypanosoma brucei

by Ya Nan Sun, Joo Hwan No, Ga Young Lee, Wei Li, Seo Young Yang, Gyongseon Yang, Thomas J. Schmidt, Jong Seong Kang and Young Ho Kim

Molecules 2016, 21(4), 480; https://doi.org/10.3390/molecules21040480 - 12 Apr 2016

Cited by 19 | Viewed by 6915

Abstract

Neglected tropical diseases (NTDs) affect over one billion people all over the world. These diseases are classified as neglected because they impact populations in areas with poor financial conditions and hence do not attract sufficient research investment. Human African Trypanosomiasis (HAT or sleeping [...] Read more.

Neglected tropical diseases (NTDs) affect over one billion people all over the world. These diseases are classified as neglected because they impact populations in areas with poor financial conditions and hence do not attract sufficient research investment. Human African Trypanosomiasis (HAT or sleeping sickness), caused by the parasite Trypanosoma brucei, is one of the NTDs. The current therapeutic interventions for T. brucei infections often have toxic side effects or require hospitalization so that they are not available in the rural environments where HAT occurs. Furthermore, parasite resistance is increasing, so that there is an urgent need to identify novel lead compounds against this infection. Recognizing the wide structural diversity of natural products, we desired to explore and identify novel antitrypanosomal chemotypes from a collection of natural products obtained from plants. In this study, 440 pure compounds from various medicinal plants were tested against T. brucei by in a screening using whole cell in vitro assays. As the result, twenty-two phenolic compounds exhibited potent activity against cultures of T. brucei. Among them, eight compounds—4, 7, 11, 14, 15, 18, 20, and 21—showed inhibitory activity against T. brucei, with IC₅₀ values below 5 µM, ranging from 0.52 to 4.70 μM. Based on these results, we attempt to establish some general trends with respect to structure-activity relationships, which indicate that further investigation and optimization of these derivatives might enable the preparation of potentially useful compounds for treating HAT. Full article

(This article belongs to the Collection Natural Products as Leads or Drugs against Neglected Tropical Diseases)

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12 pages, 1925 KiB

Open AccessArticle

Iron(III) Fluorinated Porphyrins: Greener Chemistry from Synthesis to Oxidative Catalysis Reactions

by Susana L. H. Rebelo, André M. N. Silva, Craig J. Medforth and Cristina Freire

Molecules 2016, 21(4), 481; https://doi.org/10.3390/molecules21040481 - 12 Apr 2016

Cited by 37 | Viewed by 10032

Abstract

Iron(III) fluorinated porphyrins play a central role in the biomimetics of heme enzymes and enable cleaner routes to the oxidation of organic compounds. The present work reports significant improvements in the eco-compatibility of the synthesis of 5,10,15,20-tetrakis-pentafluorophenylporphyrin (H₂TPFPP) and [...] Read more.

Iron(III) fluorinated porphyrins play a central role in the biomimetics of heme enzymes and enable cleaner routes to the oxidation of organic compounds. The present work reports significant improvements in the eco-compatibility of the synthesis of 5,10,15,20-tetrakis-pentafluorophenylporphyrin (H₂TPFPP) and the corresponding iron complex [Fe(TPFPP)Cl], and the use of [Fe(TPFPP)Cl] as an oxidation catalyst in green conditions. The preparations of H₂TPFPP and [Fe(TPFPP)Cl] typically use toxic solvents and can be made significantly greener and simpler using microwave heating and optimization of the reaction conditions. In the optimized procedure it was possible to eliminate nitrobenzene from the porphyrin synthesis and replace DMF by acetonitrile in the metalation reaction, concomitant with a significant reduction of reaction time and simplification of the purification procedure. The Fe(III)porphyrin is then tested as catalyst in the selective oxidation of aromatics at room temperature using a green oxidant (hydrogen peroxide) and green solvent (ethanol). Efficient epoxidation of indene and selective oxidation of 3,5-dimethylphenol and naphthalene to the corresponding quinones is observed. Full article

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

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11 pages, 2288 KiB

Open AccessArticle

Distinguishing Astragalus mongholicus and Its Planting Soil Samples from Different Regions by ICP-AES

by Lin Li, Sihao Zheng, Qingzhen Yang, Shilin Chen and Linfang Huang

Molecules 2016, 21(4), 482; https://doi.org/10.3390/molecules21040482 - 12 Apr 2016

Cited by 20 | Viewed by 6096

Abstract

“Daodi herb” enjoys a good reputation for its quality and clinical effects. As one of the most popular daodi herbs, Astragalus membranaceus (Fisch.) Bge var. mongholicus (Bge.) Hsiao (A. membranaceus) is popularly used for its anti-oxidant, anti-inflammatory and immune-enhancing properties. [...] Read more.

“Daodi herb” enjoys a good reputation for its quality and clinical effects. As one of the most popular daodi herbs, Astragalus membranaceus (Fisch.) Bge var. mongholicus (Bge.) Hsiao (A. membranaceus) is popularly used for its anti-oxidant, anti-inflammatory and immune-enhancing properties. In this study, we used inductively coupled plasma atomic emission spectrometry (ICP-AES) technique to investigate the inorganic elements contents in A. mongholicu and its soil samples from daodi area (Shanxi) and non-daodi areas (Inner Mongolia and Gansu). A total of 21 inorganic elements (Pb, Cd, As, Hg, Cu, P, K, Zn, Mn, Ca, Mg, Fe, Se, B, Al, Na, Cr, Ni, Ba, Ti and Sr) were simultaneously determined. Principal component analysis (PCA) was performed to differentiate A. mongholicu and soil samples from the three main producing areas. It was found that the inorganic element characteristics as well as the uptake and accumulation behavior of the three kinds of samples were significantly different. The high contents of Fe, B, Al, Na, Cr and Ni could be used as a standard in the elements fingerprint to identify daodi and non-daodi A. Mongholicus. As the main effective compounds were closely related to the pharmacodynamics activities, the inter-relationships between selected elements and components could reflect that the quality of A. Mongholicus from Shanxi were superior to others to a certain degree. This finding highlighted the usefulness of ICP-AES elemental analysis and evidenced that the inorganic element profile can be employed to evaluate the genuineness of A. mongholicus. Full article

(This article belongs to the Collection Herbal Medicine Research)

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14 pages, 900 KiB

Open AccessCommunication

PTR-MS Characterization of VOCs Associated with Commercial Aromatic Bakery Yeasts of Wine and Beer Origin

by Vittorio Capozzi, Salim Makhoul, Eugenio Aprea, Andrea Romano, Luca Cappellin, Ana Sanchez Jimena, Giuseppe Spano, Flavia Gasperi, Matteo Scampicchio and Franco Biasioli

Molecules 2016, 21(4), 483; https://doi.org/10.3390/molecules21040483 - 12 Apr 2016

Cited by 43 | Viewed by 9027

Abstract

In light of the increasing attention towards “green” solutions to improve food quality, the use of aromatic-enhancing microorganisms offers the advantage to be a natural and sustainable solution that did not negatively influence the list of ingredients. In this study, we characterize, for [...] Read more.

In light of the increasing attention towards “green” solutions to improve food quality, the use of aromatic-enhancing microorganisms offers the advantage to be a natural and sustainable solution that did not negatively influence the list of ingredients. In this study, we characterize, for the first time, volatile organic compounds (VOCs) associated with aromatic bakery yeasts. Three commercial bakery starter cultures, respectively formulated with three Saccharomyces cerevisiae strains, isolated from white wine, red wine, and beer, were monitored by a proton-transfer-reaction time-of-flight mass spectrometer (PTR-ToF-MS), a direct injection analytical technique for detecting volatile organic compounds with high sensitivity (VOCs). Two ethanol-related peaks (m/z 65.059 and 75.080) described qualitative differences in fermentative performances. The release of compounds associated to the peaks at m/z 89.059, m/z 103.075, and m/z 117.093, tentatively identified as acetoin and esters, are coherent with claimed flavor properties of the investigated strains. We propose these mass peaks and their related fragments as biomarkers to optimize the aromatic performances of commercial preparations and for the rapid massive screening of yeast collections. Full article

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

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11 pages, 3380 KiB

Open AccessArticle

Development of Singlet Oxygen Luminescence Kinetics during the Photodynamic Inactivation of Green Algae

by Tobias Bornhütter, Judith Pohl, Christian Fischer, Irena Saltsman, Atif Mahammed, Zeev Gross and Beate Röder

Molecules 2016, 21(4), 485; https://doi.org/10.3390/molecules21040485 - 13 Apr 2016

Cited by 10 | Viewed by 6336

Abstract

Recent studies show the feasibility of photodynamic inactivation of green algae as a vital step towards an effective photodynamic suppression of biofilms by using functionalized surfaces. The investigation of the intrinsic mechanisms of photodynamic inactivation in green algae represents the next step in [...] Read more.

Recent studies show the feasibility of photodynamic inactivation of green algae as a vital step towards an effective photodynamic suppression of biofilms by using functionalized surfaces. The investigation of the intrinsic mechanisms of photodynamic inactivation in green algae represents the next step in order to determine optimization parameters. The observation of singlet oxygen luminescence kinetics proved to be a very effective approach towards understanding mechanisms on a cellular level. In this study, the first two-dimensional measurement of singlet oxygen kinetics in phototrophic microorganisms on surfaces during photodynamic inactivation is presented. We established a system of reproducible algae samples on surfaces, incubated with two different cationic, antimicrobial potent photosensitizers. Fluorescence microscopy images indicate that one photosensitizer localizes inside the green algae while the other accumulates along the outer algae cell wall. A newly developed setup allows for the measurement of singlet oxygen luminescence on the green algae sample surfaces over several days. The kinetics of the singlet oxygen luminescence of both photosensitizers show different developments and a distinct change over time, corresponding with the differences in their localization as well as their photosensitization potential. While the complexity of the signal reveals a challenge for the future, this study incontrovertibly marks a crucial, inevitable step in the investigation of photodynamic inactivation of biofilms: it shows the feasibility of using the singlet oxygen luminescence kinetics to investigate photodynamic effects on surfaces and thus opens a field for numerous investigations. Full article

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

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13 pages, 4517 KiB

Open AccessArticle

Causes of Activation and Deactivation of Modified Nanogold Catalysts during Prolonged Storage and Redox Treatments

by Ekaterina Kolobova, Yulia Kotolevich, Ekaterina Pakrieva, Grigory Mamontov, Mario H. Farías, Nina Bogdanchikova, Vicente Cortés Corberán and Alexey Pestryakov

Molecules 2016, 21(4), 486; https://doi.org/10.3390/molecules21040486 - 13 Apr 2016

Cited by 18 | Viewed by 6663

Abstract

The catalytic properties of modified Au/TiO₂ catalysts for low-temperature CO oxidation are affected by deactivation and reactivation after long-term storage and by redox treatments. The effect of these phenomena on the catalysts was studied by HRTEM, BET, SEM, FTIR CO, XPS and [...] Read more.

The catalytic properties of modified Au/TiO₂ catalysts for low-temperature CO oxidation are affected by deactivation and reactivation after long-term storage and by redox treatments. The effect of these phenomena on the catalysts was studied by HRTEM, BET, SEM, FTIR CO, XPS and H₂ TPR methods. The main cause for the deactivation and reactivation of catalytic properties is the variation in the electronic state of the supported gold, mainly, the proportion of singly charged ions Au⁺. The most active samples are those with the highest proportion of singly charged gold ions, while catalysts with a high content of trivalent gold ions are inactive at low-temperatures. Active states of gold, resistant to changes caused by the reaction process and storage conditions, can be stabilized by modification of the titanium oxide support with transition metals oxides. The catalyst modified with lanthanum oxide shows the highest stability and activity. Full article

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

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11 pages, 1098 KiB

Open AccessArticle

Comparison of Antioxidant Activities of Melanin Fractions from Chestnut Shell

by Zeng-Yu Yao and Jian-Hua Qi

Molecules 2016, 21(4), 487; https://doi.org/10.3390/molecules21040487 - 22 Apr 2016

Cited by 42 | Viewed by 8219

Abstract

Chestnut shell melanin can be used as a colorant and antioxidant, and fractionated into three fractions (Fr. 1, Fr. 2, and Fr. 3) with different physicochemical properties. Antioxidant activities of the fractions were comparatively evaluated for the first time. The fractions exhibited different [...] Read more.

Chestnut shell melanin can be used as a colorant and antioxidant, and fractionated into three fractions (Fr. 1, Fr. 2, and Fr. 3) with different physicochemical properties. Antioxidant activities of the fractions were comparatively evaluated for the first time. The fractions exhibited different antioxidative potential in different evaluation systems. Fr. 1, which is only soluble in alkaline water, had the strongest peroxidation inhibition and superoxide anion scavenging activity; Fr. 2, which is soluble in alkaline water and hydrophilic organic solvents but insoluble in neutral and acidic water, had the greatest power to chelate ferrous ions; and Fr. 3, which is soluble both in hydrophilic organic solvents and in water at any pH conditions, had the greatest hydroxyl (·OH) and 1,1-diphenyl-2-picryl-hydrazyl (DPPH·) radicals scavenging abilities, reducing power, and phenolic content. The pigment fractions were superior to butylated hydroxytolune (BHT) in ·OH and DPPH· scavenging and to ethylene diamine tetraacetic acid (EDTA) in the Fe²⁺–chelation. They were inferior to BHT in peroxidation inhibition and O₂·⁻ scavenging and reducing power. However, BHT is a synthetic antioxidant and cannot play the colorant role. The melanin fractions might be used as effective biological antioxidant colorants. Full article

(This article belongs to the Section Natural Products Chemistry)

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14 pages, 2346 KiB

Open AccessArticle

Design, Synthesis and Biological Evaluation of Brain-Targeted Thiamine Disulfide Prodrugs of Ampakine Compound LCX001

by Dian Xiao, Fan-Hua Meng, Wei Dai, Zheng Yong, Jin-Qiu Liu, Xin-Bo Zhou and Song Li

Molecules 2016, 21(4), 488; https://doi.org/10.3390/molecules21040488 - 14 Apr 2016

Cited by 13 | Viewed by 8013

Abstract

Ampakine compounds have been shown to reverse opiate-induced respiratory depression by activation of amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptors. However, their pharmacological exploitations are hindered by low blood-brain barrier (BBB) permeability and limited brain distribution. Here, we explored whether thiamine disulfide prodrugs with the [...] Read more.

Ampakine compounds have been shown to reverse opiate-induced respiratory depression by activation of amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptors. However, their pharmacological exploitations are hindered by low blood-brain barrier (BBB) permeability and limited brain distribution. Here, we explored whether thiamine disulfide prodrugs with the ability of “lock-in” can be used to solve these problems. A series of thiamine disulfide prodrugs 7a–7f of ampakine compound LCX001 was synthesized and evaluated. The trials in vitro showed that prodrugs 7e, 7d, 7f possessed a certain stability in plasma and quickly decomposed in brain homogenate by the disulfide reductase. In vivo, prodrug 7e decreased the peripheral distribution of LCX001 and significantly increased brain distribution of LCX001 after i.v. administration. This compound showed 2.23- and 3.29-fold greater increases in the AUC_0-t and MRT_0-t of LCX001 in brain, respectively, than did LCX001 itself. A preliminary pharmacodynamic study indicated that the required molar dose of prodrug 7e was only one eighth that of LCX001 required to achieve the same effect in mice. These findings provide an important reference to evaluate the clinical outlook of ampakine compounds. Full article

(This article belongs to the Section Medicinal Chemistry)

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19 pages, 780 KiB

Open AccessArticle

Oxyresveratrol: Structural Modification and Evaluation of Biological Activities

by Nutputsorn Chatsumpun, Taksina Chuanasa, Boonchoo Sritularak, Vimolmas Lipipun, Vichien Jongbunprasert, Somsak Ruchirawat, Poonsakdi Ploypradith and Kittisak Likhitwitayawuid

Molecules 2016, 21(4), 489; https://doi.org/10.3390/molecules21040489 - 19 Apr 2016

Cited by 33 | Viewed by 8750

Abstract

Oxyresveratrol (2,4,3′,5′-tetrahydroxystilbene, 1), a phytoalexin present in large amounts in the heartwood of Artocarpus lacucha Buch.-Ham., has been reported to possess a wide variety of biological activities. As part of our continuing studies on the structural modification of oxyresveratrol, a library of [...] Read more.

Oxyresveratrol (2,4,3′,5′-tetrahydroxystilbene, 1), a phytoalexin present in large amounts in the heartwood of Artocarpus lacucha Buch.-Ham., has been reported to possess a wide variety of biological activities. As part of our continuing studies on the structural modification of oxyresveratrol, a library of twenty-six compounds was prepared via O-alkylation, aromatic halogenation, and electrophilic aromatic substitution. The two aromatic rings of the stilbene system of 1 can be chemically modulated by exploiting different protecting groups. Such a strategy allows for selective and exclusive modifications on either ring A or ring B. All compounds were evaluated in vitro for a panel of biological activities, including free radical scavenging activity, DNA protective properties, antiherpetic activity, inhibition of α-glucosidase and neuraminidase, and cytotoxicity against some cancer cell lines. Several derivatives were comparably active or even more potent than the parent oxyresveratrol and/or the appropriate positive controls. The partially etherified analogs 5′-hydroxy-2,3′,4-trimethoxystilbene and 3′,5′-dihydroxy-2,4-dimethoxystilbene demonstrated promising anti-herpetic and DNA protective activities, offering new leads for neuropreventive agent research, whereas 5′-hydroxy-2,3′,4,-triisopropoxystilbene displayed anti-α-glucosidase effects, providing a new lead molecule for anti-diabetic drug development. 3′,5′-Diacetoxy-2,4-diisopropoxystilbene showed potent and selective cytotoxicity against HeLa cancer cells, but the compound still needs further in vivo investigation to verify its anticancer potential. Full article

(This article belongs to the Special Issue Improvements for Resveratrol Efficacy)

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10 pages, 542 KiB

Open AccessArticle

Sesquiterpenoids and Diterpenoids from the Wood of Cunninghamia konishii and Their Inhibitory Activities against NO Production

by Chi-I Chang, Chien-Chih Chen, Che-Yi Chao, Sheng-Yang Wang, Hsun-Shuo Chang, Ping-Jyun Sung, Guan-Jhong Huang, Yen-Cheng Li and Yueh-Hsiung Kuo

Molecules 2016, 21(4), 490; https://doi.org/10.3390/molecules21040490 - 13 Apr 2016

Cited by 1 | Viewed by 5334

Abstract

Three new sesquiterpenoids, 2α-hydroxy-3,3,6α,9β-tetramethyltricyclo[4,3,2^1,4]undecane (1), 11-acetoxyeudesman-4β-ol (4), and 2α,3β-dihydroxy-4β-methyl-6,8,10-cadinatriene (6), four known sesquiterpenoids (2, 3, 5, and 7), together with eight known diterpenoids (8–15), were isolated from the wood of Cunninghamia konishii. Their structures were determined by detailed analysis of spectroscopic [...] Read more.

Three new sesquiterpenoids, 2α-hydroxy-3,3,6α,9β-tetramethyltricyclo[4,3,2^1,4]undecane (1), 11-acetoxyeudesman-4β-ol (4), and 2α,3β-dihydroxy-4β-methyl-6,8,10-cadinatriene (6), four known sesquiterpenoids (2, 3, 5, and 7), together with eight known diterpenoids (8–15), were isolated from the wood of Cunninghamia konishii. Their structures were determined by detailed analysis of spectroscopic data and comparison with the data of known analogues. Four sesquiterpenoids (1, 4, 5, and 6) and all the diterpenoids (8–15) were evaluated for inhibition of nitric oxide production in lipopolysaccharides (LPS)-activated RAW 264.7 macrophages and the results showed that compounds 10 and 15 exhibited moderate inhibitory activities against nitric oxide production. Full article

(This article belongs to the Section Natural Products Chemistry)

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16 pages, 2874 KiB

Open AccessArticle

Novel Anthranilamide-Based FXa Inhibitors: Drug Design, Synthesis and Biological Evaluation

by Wenzhi Wang, Jing Yuan, Xiaoli Fu, Fancui Meng, Shijun Zhang, Weiren Xu, Yongnan Xu and Changjiang Huang

Molecules 2016, 21(4), 491; https://doi.org/10.3390/molecules21040491 - 14 Apr 2016

Cited by 13 | Viewed by 7182

Abstract

Factor Xa (FXa) plays a significant role in the blood coagulation cascade and it has become a promising target for anticoagulation drugs. Three oral direct FXa inhibitors have been approved by the FDA for treating thrombotic diseases. By structure-activity relationship (SAR) analysis upon [...] Read more.

Factor Xa (FXa) plays a significant role in the blood coagulation cascade and it has become a promising target for anticoagulation drugs. Three oral direct FXa inhibitors have been approved by the FDA for treating thrombotic diseases. By structure-activity relationship (SAR) analysis upon these FXa inhibitors, a series of novel anthranilamide-based FXa inhibitors were designed and synthesized. According to our study, compounds 1a, 1g and 1s displayed evident FXa inhibitory activity and excellent selectivity over thrombin in in vitro inhibition activities studies. Compounds 1g and 1s also exhibited pronounced anticoagulant activities in in vitro anticoagulant activity studies. Full article

(This article belongs to the Section Medicinal Chemistry)

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11 pages, 1302 KiB

Open AccessArticle

UHPLC-MS/MS Determination, Pharmacokinetic, and Bioavailability Study of Taxifolin in Rat Plasma after Oral Administration of its Nanodispersion

by Chun-Juan Yang, Zhi-Bin Wang, Ying-Ying Mi, Ming-Jie Gao, Jin-Nan Lv, Yong-Hai Meng, Bing-You Yang and Hai-Xue Kuang

Molecules 2016, 21(4), 494; https://doi.org/10.3390/molecules21040494 - 14 Apr 2016

Cited by 43 | Viewed by 7121

Abstract

A rapid and sensitive LC-MS/MS method based on the Triple Quad system has been developed and validated for the determination and pharmacokinetics of taxifolin and its nanodispersion in rat plasma. Taxifolin plasma samples along with butylparaben (internal standard) were pre-treated by liquid-liquid extraction [...] Read more.

A rapid and sensitive LC-MS/MS method based on the Triple Quad system has been developed and validated for the determination and pharmacokinetics of taxifolin and its nanodispersion in rat plasma. Taxifolin plasma samples along with butylparaben (internal standard) were pre-treated by liquid-liquid extraction with ethyl acetate, and then separated on a SB-C₁₈ RRHD column (150 mm × 2.1 mm × 1.8 μm) using isocratic elution with a run time of 3.0 min. The mobile phase was acetonitrile–water (90:10, v/v) containing 5 mM ammonium acetate at a flow rate of 0.4 mL/min. Quantification of taxifolin was performed by the electrospray ionization tandem mass spectrometry in the multiple reaction monitoring (MRM) mode with negative atmospheric ionization at m/z 303.0→285.0 for taxifolin and 193.1→92.0 for I.S., respectively. The calibration curve of taxifolin showed good linearity over a concentration range of 5.0–4280 ng/mL with a correlation coefficient of 0.9995. The limit of quantification (LLOQ) was 5.0 ng/mL. Intra-day, inter-day precision and accuracy (percent relative to standard deviation) were all within 8% at three concentration levels. A total recovery of taxifolin and I.S. was beyond 75%. The present LC-MS/MS method was successfully applied to pharmacokinetic studies of taxifolin after intravenous administration of taxifolin, oral administration of its physical mixture and nanodispersion. The absolute bioavailability of taxifolin was calculated as 0.75% for taxifolin nanodispersion and 0.49% for taxifolin, respectively. Full article

(This article belongs to the Section Natural Products Chemistry)

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23 pages, 5539 KiB

Open AccessArticle

Pharmacogenomics of Scopoletin in Tumor Cells

by Ean-Jeong Seo, Mohamed Saeed, Betty Yuen Kwan Law, An Guo Wu, Onat Kadioglu, Henry Johannes Greten and Thomas Efferth

Molecules 2016, 21(4), 496; https://doi.org/10.3390/molecules21040496 - 15 Apr 2016

Cited by 41 | Viewed by 11396

Abstract

Drug resistance and the severe side effects of chemotherapy necessitate the development of novel anticancer drugs. Natural products are a valuable source for drug development. Scopoletin is a coumarin compound, which can be found in several Artemisia species and other plant genera. Microarray-based [...] Read more.

Drug resistance and the severe side effects of chemotherapy necessitate the development of novel anticancer drugs. Natural products are a valuable source for drug development. Scopoletin is a coumarin compound, which can be found in several Artemisia species and other plant genera. Microarray-based RNA expression profiling of the NCI cell line panel showed that cellular response of scopoletin did not correlate to the expression of ATP-binding cassette (ABC) transporters as classical drug resistance mechanisms (ABCB1, ABCB5, ABCC1, ABCG2). This was also true for the expression of the oncogene EGFR and the mutational status of the tumor suppressor gene, TP53. However, mutations in the RAS oncogenes and the slow proliferative activity in terms of cell doubling times significantly correlated with scopoletin resistance. COMPARE and hierarchical cluster analyses of transcriptome-wide mRNA expression resulted in a set of 40 genes, which all harbored binding motifs in their promoter sequences for the transcription factor, NF-κB, which is known to be associated with drug resistance. RAS mutations, slow proliferative activity, and NF-κB may hamper its effectiveness. By in silico molecular docking studies, we found that scopoletin bound to NF-κB and its regulator IκB. Scopoletin activated NF-κB in a SEAP-driven NF-κB reporter cell line, indicating that NF-κB might be a resistance factor for scopoletin. In conclusion, scopoletin might serve as lead compound for drug development because of its favorable activity against tumor cells with ABC-transporter expression, although NF-κB activation may be considered as resistance factor for this compound. Further investigations are warranted to explore the full therapeutic potential of this natural product. Full article

(This article belongs to the Collection Herbal Medicine Research)

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12 pages, 928 KiB

Open AccessArticle

New Inducible Nitric Oxide Synthase and Cyclooxygenase-2 Inhibitors, Nalidixic Acid Linked to Isatin Schiff Bases via Certain l-Amino Acid Bridges

by Ahmed M. Naglah, Atallah F. Ahmed, Zhi-Hong Wen, Mohamed A. Al-Omar, Abd El-Galil E. Amr and Atef Kalmouch

Molecules 2016, 21(4), 498; https://doi.org/10.3390/molecules21040498 - 15 Apr 2016

Cited by 20 | Viewed by 6070

Abstract

A series of new Schiff bases were synthesized by condensation of isatins with the nalidixic acid-l-amino acid hydrazides. Prior to hydrazide formation, a peptide linkage has been prepared via coupling of nalidixic acid with appropriate l-amino acid methyl esters to [...] Read more.

A series of new Schiff bases were synthesized by condensation of isatins with the nalidixic acid-l-amino acid hydrazides. Prior to hydrazide formation, a peptide linkage has been prepared via coupling of nalidixic acid with appropriate l-amino acid methyl esters to yield 3a–c. The chemical structures of the new Schiff bases (5b and 5d–h) were confirmed by means of IR, NMR, mass spectroscopic, and elemental analyses. The anti-inflammatory activity of these Schiff bases was evaluated via measurement of the expressed inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in the lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells model. The Schiff bases exhibited significant dual inhibitory effect against the induction of the pro-inflammatory iNOS and COX-2 proteins with variable potencies. However, they strongly down-regulated the iNOS expression to the level of 16.5% ± 7.4%–42.2% ± 19.6% compared to the effect on COX-2 expression (<56.4% ± 3.1% inhibition) at the same concentration (10 μM). The higher iNOS inhibition activity of the tested Schiff bases, relative to that of COX-2, seems to be a reflection of the combined suppressive effects exerted by their nalidixic acid, isatins (4a–c), and l-amino acid moieties against iNOS expression. These synthesized nalidixic acid-l-amino acid-isatin conjugates can be regarded as a novel class of anti-inflammatory antibacterial agents. Full article

(This article belongs to the Section Medicinal Chemistry)

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15 pages, 3685 KiB

Open AccessArticle

Calculation of Relative Binding Free Energy in the Water-Filled Active Site of Oligopeptide-Binding Protein A

by Manuela Maurer, Stephanie B. A. De Beer and Chris Oostenbrink

Molecules 2016, 21(4), 499; https://doi.org/10.3390/molecules21040499 - 15 Apr 2016

Cited by 22 | Viewed by 7234

Abstract

The periplasmic oligopeptide binding protein A (OppA) represents a well-known example of water-mediated protein-ligand interactions. Here, we perform free-energy calculations for three different ligands binding to OppA, using a thermodynamic integration approach. The tripeptide ligands share a high structural similarity (all have the [...] Read more.

The periplasmic oligopeptide binding protein A (OppA) represents a well-known example of water-mediated protein-ligand interactions. Here, we perform free-energy calculations for three different ligands binding to OppA, using a thermodynamic integration approach. The tripeptide ligands share a high structural similarity (all have the sequence KXK), but their experimentally-determined binding free energies differ remarkably. Thermodynamic cycles were constructed for the ligands, and simulations conducted in the bound and (freely solvated) unbound states. In the unbound state, it was observed that the difference in conformational freedom between alanine and glycine leads to a surprisingly slow convergence, despite their chemical similarity. This could be overcome by increasing the softness parameter during alchemical transformations. Discrepancies remained in the bound state however, when comparing independent simulations of the three ligands. These difficulties could be traced to a slow relaxation of the water network within the active site. Fluctuations in the number of water molecules residing in the binding cavity occur mostly on a timescale larger than the simulation time along the alchemical path. After extensive simulations, relative binding free energies that were converged to within thermal noise could be obtained, which agree well with available experimental data. Full article

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

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16 pages, 6156 KiB

Open AccessArticle

Effect of Sodium Dodecyl Sulfate Adsorption on the Behavior of Water inside Single Walled Carbon Nanotubes with Dissipative Particle Dynamics Simulation

by Minh D. Vo and Dimitrios V. Papavassiliou

Molecules 2016, 21(4), 500; https://doi.org/10.3390/molecules21040500 - 15 Apr 2016

Cited by 15 | Viewed by 7569

Abstract

Dissipative particle dynamics (DPD) simulations were utilized to investigate the ability of sodium dodecyl sulfate (SDS) to adsorb inside a single-walled, arm-chair carbon nanotube (SWCNT), as well as the effect of surfactant on the properties of water inside the SWCNT. The diameter of [...] Read more.

Dissipative particle dynamics (DPD) simulations were utilized to investigate the ability of sodium dodecyl sulfate (SDS) to adsorb inside a single-walled, arm-chair carbon nanotube (SWCNT), as well as the effect of surfactant on the properties of water inside the SWCNT. The diameter of the SWCNT varied from 1 to 5 nm. The radial and axial density profiles of water inside the SWCNTs were computed and compared with published molecular dynamics results. The average residence time and diffusivity were also calculated to show the size effect on mobility of water inside the SWCNT. It was found that nanotubes with diameter smaller than 3 nm do not allow SDS molecules to enter the SWCNT space. For larger SWCNT diameter, SDS adsorbed inside and outside the nanotube. When SDS was adsorbed in the hollow part of the SWCNT, the behavior of water inside the nanotube was found to be significantly changed. Both radial and axial density profiles of water inside the SWCNT fluctuated strongly and were different from those in bulk phase. In addition, SDS molecules increased the retention of water beads inside SWCNT (d ≥ 3nm) while water diffusivity was decreased. Full article

(This article belongs to the Section Molecular Diversity)

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12 pages, 1234 KiB

Open AccessArticle

LC-MS/MS Analysis and Pharmacokinetics of Sodium (±)-5-Bromo-2-(α-hydroxypentyl) Benzoate (BZP), an Innovative Potent Anti-Ischemic Stroke Agent in Rats

by Xin Tian, Bingjie Liu, Yuhai Zhang, Hongmeng Li, Jingyao Wei, Gaoju Wang, Junbiao Chang and Hailing Qiao

Molecules 2016, 21(4), 501; https://doi.org/10.3390/molecules21040501 - 16 Apr 2016

Cited by 11 | Viewed by 6398

Abstract

A rapid, sensitive and selective liquid chromatography-triple quadrupole mass spectrometry (LC-MS/MS) method was developed and validated for the simultaneous determination of sodium (±)-5-Bromo-2-(α-hydroxypentyl) benzoate (BZP) and its active metabolite 3-butyl-6-bromo-1(3H)-isobenzofuranone (Br-NBP) in rat plasma using potassium 2-(1-hydroxypentyl)-benzoate (PHPB) and l-3-n-butylphthalide (NBP) [...] Read more.

A rapid, sensitive and selective liquid chromatography-triple quadrupole mass spectrometry (LC-MS/MS) method was developed and validated for the simultaneous determination of sodium (±)-5-Bromo-2-(α-hydroxypentyl) benzoate (BZP) and its active metabolite 3-butyl-6-bromo-1(3H)-isobenzofuranone (Br-NBP) in rat plasma using potassium 2-(1-hydroxypentyl)-benzoate (PHPB) and l-3-n-butylphthalide (NBP) as internal standards (IS). Chromatographic separation was achieved on a Hypersil GOLD C18 column using a gradient elution of ammonium acetate and methanol at a flow rate of 0.2 mL/min. Good linearity was achieved within the wide concentration range of 5–10,000 ng/mL. The intra-day and inter-day precision was less than 8.71% and the accuracy was within −8.53% and 6.38% in quality control and the lower limit of quantitation samples. BZP and Br-NBP were stable during the analysis and the storage period. The method was successfully applied to pharmacokinetic studies of BZP in Sprague-Dawley rats for the first time. After a single intravenous administration of BZP at the dose of 0.75 mg/kg, the plasma concentration of BZP and Br-NBP declined rapidly and the AUC_0-t of BZP was significantly greater in female rats compared to male rats (p < 0.05). The data presented in this study serve as a firm basis for further investigation of BZP in both preclinical and clinical phases. Full article

(This article belongs to the Section Medicinal Chemistry)

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13 pages, 1797 KiB

Open AccessArticle

Potential of the Endophytic Fungus Phialocephala fortinii Rac56 Found in Rhodiola Plants to Produce Salidroside and p-Tyrosol

by Jinlong Cui, Tingting Guo, Jianbin Chao, Mengliang Wang and Junhong Wang

Molecules 2016, 21(4), 502; https://doi.org/10.3390/molecules21040502 - 16 Apr 2016

Cited by 37 | Viewed by 9113

Abstract

2-(4-Hydroxyphenyl)ehyl-β-d-glucopyranoside (salidroside) and 4-(2-hydroxyethyl)phenol (p-tyrosol) are famous food and medicine additives originally derived from alpine Rhodiola plants. Salidroside or p-tyrosol production by the endophytic fungus Rac56 (Phialocephala fortinii) was confirmed by UPLC/Q-TOF-MS and ¹H-NMR. The [...] Read more.

2-(4-Hydroxyphenyl)ehyl-β-d-glucopyranoside (salidroside) and 4-(2-hydroxyethyl)phenol (p-tyrosol) are famous food and medicine additives originally derived from alpine Rhodiola plants. Salidroside or p-tyrosol production by the endophytic fungus Rac56 (Phialocephala fortinii) was confirmed by UPLC/Q-TOF-MS and ¹H-NMR. The fermentation conditions were optimized by orthogonal design using data processing system software. The broth fermentation results showed that salidroside and p-tyrosol extraction yields from Rac56 were stable and reached 1.729 ± 0.06 mg and 1.990 ± 0.05 mg per mL of culture medium, respectively. The optimal conditions for salidroside and p-tyrosol production in fermentation culture of Rac56 were determined to be 25 °C, pH values of 7 and 5, Czapek-Dox culture medium volumes of 150 mL and 50 mL in 250 mL flasks, rotation speeds of 100× g and 200× g, and fermentation durations of 7 and 15 days, respectively. Under these optimal conditions, stable yields of 2.339 ± 0.1093 mg and 2.002 ± 0.0009 mg per mL of culture medium of salidroside and p-tyrosol, respectively, were obtained, indicating that the P. fortinii Rac56 strain is a promising source of these compounds. Full article

(This article belongs to the Section Metabolites)

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13 pages, 2175 KiB

Open AccessArticle

Rearrangements of Cycloalkenyl Aryl Ethers

by Mercedesz Törincsi, Melinda Nagy, Tamás Bihari, András Stirling, Pál Kolonits and Lajos Novak

Molecules 2016, 21(4), 503; https://doi.org/10.3390/molecules21040503 - 19 Apr 2016

Cited by 3 | Viewed by 6946

Abstract

Rearrangement reactions of cycloalkenyl phenol and naphthyl ethers and the acid-catalyzed cyclization of the resulting product were investigated. Claisen rearrangement afforded 2-substituted phenol and naphthol derivatives. Combined Claisen and Cope rearrangement resulted in the formation of 4-substituted phenol and naphthol derivatives. In the [...] Read more.

Rearrangement reactions of cycloalkenyl phenol and naphthyl ethers and the acid-catalyzed cyclization of the resulting product were investigated. Claisen rearrangement afforded 2-substituted phenol and naphthol derivatives. Combined Claisen and Cope rearrangement resulted in the formation of 4-substituted phenol and naphthol derivatives. In the case of cycloocthylphenyl ether the consecutive Claisen and Cope rearrangements were followed by an alkyl migration. The mechanism of this novel rearrangement reaction is also discussed. Full article

(This article belongs to the Special Issue Pericyclic Reactions)

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11 pages, 1159 KiB

Open AccessArticle

Contact and Repellent Activities of the Essential Oil from Juniperus formosana against Two Stored Product Insects

by Shanshan Guo, Wenjuan Zhang, Junyu Liang, Chunxue You, Zhufeng Geng, Chengfang Wang and Shushan Du

Molecules 2016, 21(4), 504; https://doi.org/10.3390/molecules21040504 - 16 Apr 2016

Cited by 44 | Viewed by 9203

Abstract

The chemical composition of the essential oil from Juniperus formosana leaves and its contact and repellent activities against Tribolium castaneum and Liposcelis bostrychophila adults were investigated. The essential oil of J. formosana leaves was obtained by hydrodistillation and analyzed by GC-MS. A total [...] Read more.

The chemical composition of the essential oil from Juniperus formosana leaves and its contact and repellent activities against Tribolium castaneum and Liposcelis bostrychophila adults were investigated. The essential oil of J. formosana leaves was obtained by hydrodistillation and analyzed by GC-MS. A total of 28 components were identified and the main compounds in the essential oil were α-pinene (21.66%), 4-terpineol (11.25%), limonene (11.00%) and β-phellandrene (6.63%). The constituents α-pinene, 4-terpineol and d-limonene were isolated from the essential oil. It was found that the essential oil exhibited contact activity against T. castaneum and L. bostrychophila adults (LD₅₀ = 29.14 μg/adult and 81.50 µg/cm², respectively). The compound 4-terpineol exhibited the strongest contact activity (LD₅₀ = 7.65 μg/adult). In addition, data showed that at 78.63 nL/cm², the essential oil and the three isolated compounds strongly repelled T. castaneum adults. The compounds α-pinene and d-limonene reached the same level (Class V) of repellency as DEET (p = 0.396 and 0.664) against L. bostrychophila at 63.17 nL/cm² after 2 h treatment. The results indicate that the essential oil and the isolated compounds have potential to be developed into natural insecticides and repellents to control insects in stored products. Full article

(This article belongs to the Collection Herbal Medicine Research)

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13 pages, 3695 KiB

Open AccessArticle

A Green Ultrasound Synthesis, Characterization and Antibacterial Evaluation of 1,4-Disubstituted 1,2,3-Triazoles Tethering Bioactive Benzothiazole Nucleus

by Nadjet Rezki

Molecules 2016, 21(4), 505; https://doi.org/10.3390/molecules21040505 - 18 Apr 2016

Cited by 46 | Viewed by 5979

Abstract

The synthesis of N-(benzo[d]thiazol-2-yl)-2-(4-substituted-1H-1,2,3-triazol-1-yl)acetamides 5a–r via the 1,3-dipolar cycloaddition reaction between 2-azido-N-(benzo[d]thiazol-2-yl)acetamide derivatives 3a–c and different alkynes were performed in the presence and absence of ultrasound irradiation. The synthesis was carried out using t [...] Read more.

The synthesis of N-(benzo[d]thiazol-2-yl)-2-(4-substituted-1H-1,2,3-triazol-1-yl)acetamides 5a–r via the 1,3-dipolar cycloaddition reaction between 2-azido-N-(benzo[d]thiazol-2-yl)acetamide derivatives 3a–c and different alkynes were performed in the presence and absence of ultrasound irradiation. The synthesis was carried out using t-BuOH/H₂O (1:1, v/v) as reaction solvents and CuSO₄·5H₂O/sodium ascorbate as the catalyst. The copper catalyst was implemented to provide the regioselective 1,4-disubstituted 1,2,3-triazoles 5a–r. Significant reductions in reaction times with comparably higher yields were observed when the reactions were carried out under ultrasound irradiation. The structures of the newly synthesized 1,2,3-triazoles were elucidated by IR, NMR, MS, and elemental analyses. They were also screened for their antimicrobial activity against three gram-positive (Streptococcus pneumonia, Bacillus subtilis, and Staphylococcus aureus), three gram-negative (Pseudomonas aeuroginosa, Escherichia coli, and Klebsiella pneumonia), and two fungal strains (Aspergillus fumigates and Candida albicans). Most of the tested compounds displayed promising antimicrobial activities at a Minimum Inhibition Concentration (MIC) of 4–16 μg/mL. Full article

(This article belongs to the Collection Heterocyclic Compounds)

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9 pages, 916 KiB

Open AccessArticle

Evaluation of Olive Fruit Lipoxygenase Extraction Protocols on 9- and 13-Z,E-HPODE Formation

by Barbara Soldo, Matilda Šprung, Gloria Mušac, Maja Pavela-Vrančić and Ivica Ljubenkov

Molecules 2016, 21(4), 506; https://doi.org/10.3390/molecules21040506 - 20 Apr 2016

Cited by 4 | Viewed by 5273

Abstract

In plant tissues, enzymes implicated in the lipoxygenase (LOX) pathway are responsible for the hydroperoxydation of polyunsaturated fatty acids, ultimately leading to the production of small chemical species involved in several physiological processes. During industrial olive oil production, these enzymes are activated upon [...] Read more.

In plant tissues, enzymes implicated in the lipoxygenase (LOX) pathway are responsible for the hydroperoxydation of polyunsaturated fatty acids, ultimately leading to the production of small chemical species involved in several physiological processes. During industrial olive oil production, these enzymes are activated upon crushing and grinding of olive fruit tissue, subsequently leading to the synthesis of volatile compounds responsible for the positive aroma and flavor of the oil. An investigation of LOX activity during olive fruit ripening and malaxation could assist in the production of oils with favorable aroma and taste. Therefore, a reliable method for olive LOX purification is crucial. Here we report a critical review of six LOX extraction protocols, two of which have shown minimum enzyme activity, possibly leading to misconceptions in the interpretation of experimental data. Future research concerning olive LOX should employ extraction methods that preserve enzyme activity. Full article

(This article belongs to the Section Natural Products Chemistry)

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11 pages, 1657 KiB

Open AccessArticle

The Effect of an Optimized Wet Milling Technology on the Crystallinity, Morphology and Dissolution Properties of Micro- and Nanonized Meloxicam

by Csilla Bartos, Piroska Szabó-Révész, Csaba Bartos, Gábor Katona, Orsolya Jójárt-Laczkovich and Rita Ambrus

Molecules 2016, 21(4), 507; https://doi.org/10.3390/molecules21040507 - 21 Apr 2016

Cited by 37 | Viewed by 6547

Abstract

This article reports on the effects of a new combined wet milling technique on the physicochemical properties of meloxicam (MEL). The influence of milling time on the particle size, the crystallinity, the morphology and the dissolution rate of MEL has been studied in [...] Read more.

This article reports on the effects of a new combined wet milling technique on the physicochemical properties of meloxicam (MEL). The influence of milling time on the particle size, the crystallinity, the morphology and the dissolution rate of MEL has been studied in the presence and absence of polyvinyl alcohol (PVA) as a stabilizer agent. Micronized MEL particles were produced in aqueous medium which did not contain additive after milling for 10 min. For nanonization an additive and longer milling time were required. After particle size determination the structural and morphological characterization of the wet milled, dried products containing MEL were studied. X-ray powder diffractometry (XRPD) and differential scanning calorimetry (DSC) examinations revealed the change in the crystallinity of MEL. Scanning electron microscopy (SEM) images showed that aggregates of nanosized MEL particles were formed, regardless of the presence of PVA. The nanonized MEL crystals (D₅₀ = 126 nm) exhibited a regular shape and a smooth surface. The increased specific surface area resulted in a high dissolution rate and concentration of free MEL. According to the results, the produced samples could be applied as a basic material (micronized MEL) and intermediate product (micronized and nanonized MEL with PVA) for the design of dosage forms. Full article

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

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14 pages, 1515 KiB

Open AccessArticle

1-(2,3-Dibenzimidazol-2-ylpropyl)-2-methoxybenzene Is a Syk Inhibitor with Anti-Inflammatory Properties

by Eunji Kim, Young-Jin Son, Yanyan Yang, Ting Shen, Ikyon Kim, Adithan Aravinthan, Jong-Hoon Kim and Jae Youl Cho

Molecules 2016, 21(4), 508; https://doi.org/10.3390/molecules21040508 - 18 Apr 2016

Cited by 8 | Viewed by 6862

Abstract

Inflammation is the protective action of our bodies against external pathogens by recognition of pathogen-associated molecular patterns (PAMPs) via pattern recognition receptors (PRRs). Proper regulation of inflammatory responses is required to maintain our body’s homeostasis, as well as there are demands to develop [...] Read more.

Inflammation is the protective action of our bodies against external pathogens by recognition of pathogen-associated molecular patterns (PAMPs) via pattern recognition receptors (PRRs). Proper regulation of inflammatory responses is required to maintain our body’s homeostasis, as well as there are demands to develop proper acute or chronic inflammation. In this study, we elucidated the regulatory mechanism of NF-κB-mediated inflammatory responses by a novel compound, 1-(2,3-dibenzimidazol-2-ylpropyl)-2-methoxybenzene (DBMB). We found that DBMB suppressed inflammatory mediators, nitric oxide (NO) and prostaglandin E₂ (PGE₂), reacted to exposure to a number of toll like receptor (TLR) ligands. Such observations occurred following to decreased mRNA expression of several pro-inflammatory mediators, and such diminished mRNA levels were caused by inhibited transcriptional factor nuclear factor (NF)-κB, as evaluated by luciferase reporter assay and molecular biological approaches. To find the potential targets of DBMB, we screened phosphorylated forms of NF-κB signal molecules: inhibitor of κBα (IκBα), IκB kinase (IKK)α/β, Akt, 3-phosphoinositide dependent protein kinase-1 (PDK1), p85, and spleen tyrosine kinase (Syk). We found that DBMB treatment could suppress signal transduction through these molecules. Additionally, we conducted in vitro kinase assays using immunoprecipitated Syk and its substrate, p85. Consequently, we could say that DBMB clearly suppressed the kinase activity of Syk kinase activity. Together, our results demonstrate that synthetic DBMB has an effect on the inflammatory NF-κB signaling pathway and suggest the potential for clinical use in the treatment of inflammatory diseases. Full article

(This article belongs to the Section Medicinal Chemistry)

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13 pages, 5316 KiB

Open AccessArticle

Properties of the Sodium Naproxen-Lactose-Tetrahydrate Co-Crystal upon Processing and Storage

by Ioana Sovago, Wenbo Wang, Danwen Qiu, Dhara Raijada, Jukka Rantanen, Holger Grohganz, Thomas Rades, Andrew D. Bond and Korbinian Löbmann

Molecules 2016, 21(4), 509; https://doi.org/10.3390/molecules21040509 - 19 Apr 2016

Cited by 18 | Viewed by 9682

Abstract

Co-crystals and co-amorphous systems are two strategies to improve the physical properties of an active pharmaceutical ingredient and, thus, have recently gained considerable interest both in academia and the pharmaceutical industry. In this study, the behavior of the recently identified sodium naproxen-lactose-tetrahydrate co-crystal [...] Read more.

Co-crystals and co-amorphous systems are two strategies to improve the physical properties of an active pharmaceutical ingredient and, thus, have recently gained considerable interest both in academia and the pharmaceutical industry. In this study, the behavior of the recently identified sodium naproxen-lactose-tetrahydrate co-crystal and the co-amorphous mixture of sodium, naproxen, and lactose was investigated. The structure of the co-crystal is described using single-crystal X-ray diffraction. The structural analysis revealed a monoclinic lattice, space group P2_1, with the asymmetric unit containing one molecule of lactose, one of naproxen, sodium, and four water molecules. Upon heating, it was observed that the co-crystal transforms into a co-amorphous system due to the loss of its crystalline bound water. Dehydration and co-amorphization were studied using synchrotron X-ray radiation and thermogravimetric analysis (TGA). Subsequently, different processing techniques (ball milling, spray drying, and dehydration) were used to prepare the co-amorphous mixture of sodium, naproxen, and lactose. X-ray powder diffraction (XRPD) revealed the amorphous nature of the mixtures after preparation. Differential scanning calorimetry (DSC) analysis showed that the blends were single-phase co-amorphous systems as indicated by a single glass transition temperature. The samples were subsequently tested for physical stability under dry (silica gel at 25 and 40 °C) and humid conditions (25 °C/75% RH). The co-amorphous samples stored at 25 °C/75% RH quickly recrystallized into the co-crystalline state. On the other hand, the samples stored under dry conditions remained physically stable after five months of storage, except the ball milled sample stored at 40 °C which showed signs of recrystallization. Under these dry conditions, however, the ball-milled co-amorphous blend crystallized into the individual crystalline components. Full article

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

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13 pages, 859 KiB

Open AccessArticle

Synthesis and Biological Evaluation of Novel ^99mTc(CO)₃-Labeled Thymidine Analogs as Potential Probes for Tumor Proliferation Imaging

by Xiaojiang Duan, Teli Liu, Yichun Zhang and Junbo Zhang

Molecules 2016, 21(4), 510; https://doi.org/10.3390/molecules21040510 - 19 Apr 2016

Cited by 10 | Viewed by 4781

Abstract

Achieving a ^99mTc labeled thymidine radiotracer for single photon emission tomography (SPECT) is considered to be of interest. In this study, four novel thymidine analogs, 6a, 6b, 6c and 6d, were successfully synthesized via “click reaction” route and then [...] Read more.

Achieving a ^99mTc labeled thymidine radiotracer for single photon emission tomography (SPECT) is considered to be of interest. In this study, four novel thymidine analogs, 6a, 6b, 6c and 6d, were successfully synthesized via “click reaction” route and then radiolabeled using a [^99mTc(CO)₃]⁺ core to prepare the corresponding ^99mTc(CO)₃ complexes in high yields. These complexes were hydrophilic and had good in vitro stability. Biodistribution of these complexes in mice bearing S180 tumors showed that all of them exhibited accumulation in the tumors, suggesting that they would be potential tumor imaging agents. Full article

(This article belongs to the Section Medicinal Chemistry)

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14 pages, 2120 KiB

Open AccessArticle

Effect of Food Emulsifiers on Aroma Release

by Jia-Jia Li, Man Dong, Yan-Long Liu, Lu-Lu Zhang, Yan Zhang, Zi-Yu Yang, Jing-Nan Ren, Si-Yi Pan and Gang Fan

Molecules 2016, 21(4), 511; https://doi.org/10.3390/molecules21040511 - 22 Apr 2016

Cited by 14 | Viewed by 9725

Abstract

This study aimed to determine the influence of different emulsifiers or xanthan-emulsifier systems on the release of aroma compounds. Solid-phase microextraction (SPME) and GC-MS were used to study the effects of varying concentrations of xanthan gum, sucrose fatty acid ester, Tween 80 and [...] Read more.

This study aimed to determine the influence of different emulsifiers or xanthan-emulsifier systems on the release of aroma compounds. Solid-phase microextraction (SPME) and GC-MS were used to study the effects of varying concentrations of xanthan gum, sucrose fatty acid ester, Tween 80 and soybean lecithin on the release of seven aroma compounds. The effects of the emulsifier systems supplemented with xanthan gum on aroma release were also studied in the same way. The results showed varying degrees of influence of sucrose fatty acid ester, soybean lecithin, Tween 80 and xanthan gum on the release of aroma compounds. Compared with other aroma compounds, ethyl acetate was more likely to be conserved in the solution system, while the amount of limonene released was the highest among these seven aroma compounds. In conclusion, different emulsifiers and complexes showed different surface properties that tend to interact with different aroma molecules. The present studies showed that the composition and structure of emulsifiers and specific interactions between emulsifiers and aroma molecules have significant effects on aroma release. Full article

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

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10 pages, 1473 KiB

Open AccessArticle

MP-V1 from the Venom of Social Wasp Vespula vulgaris Is a de Novo Type of Mastoparan that Displays Superior Antimicrobial Activities

by Yangseon Kim, Minky Son, Eun-Young Noh, Soonok Kim, Changmu Kim, Joo-Hong Yeo, Chanin Park, Keun Woo Lee and Woo Young Bang

Molecules 2016, 21(4), 512; https://doi.org/10.3390/molecules21040512 - 19 Apr 2016

Cited by 18 | Viewed by 6188

Abstract

Mastoparans from the venom of social wasps have attracted considerable attention as effective antibiotic candidates. In this study, mastoparan V1 (MP-V1) from Vespula vulgaris was first disclosed to have a peptide amino acid sequence distinct from typical mastoparans and its biochemical properties and [...] Read more.

Mastoparans from the venom of social wasps have attracted considerable attention as effective antibiotic candidates. In this study, mastoparan V1 (MP-V1) from Vespula vulgaris was first disclosed to have a peptide amino acid sequence distinct from typical mastoparans and its biochemical properties and antimicrobial effects were compared with those of typical mastoparans MP-L, -X(V) and -B. Circular dichroism (CD) spectroscopy revealed that MP-V1 and -X(V) form more stable α-helical conformations in lipid membrane-like environments than MP-L and -B. In parallel, these two also showed more effective antimicrobial activities against the pathogens than did MP-L and -B. Although MP-V1 had a less stable α-helical conformation than MP-X(V), it showed stronger antimicrobial effects against Streptococcus mutans and Salmonella enterica than MP-X(V). In the meantime, analysis of hemolytic activity revealed a range of doses (~50 μM) that exhibited little potent cytotoxicity on human erythrocytes. Finally, the atypical MP-V1 peptide amino acid sequence provided important clues to understanding its antimicrobial mechanism from a structural perspective. Therefore, it has been concluded that MP-V1 is a de novo type of mastoparan with superior antimicrobial activities against both pathogenic bacteria and fungi, which may be useful in developing multipurpose antimicrobial drugs against infectious diseases. Full article

(This article belongs to the Special Issue Natural Toxins)

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15 pages, 1513 KiB

Open AccessArticle

Comparison of Antioxidant Capability after Isopropanol Salting-Out Pretreatment and n-Butanol Partition Extraction, and Identification and Evaluation of Antioxidants of Sedum formosanum N.E.Br.

by Jung-Hui Chen, Wen-Hui Lai, Shang-Dung Lin, Cheng-Fong Lan, Shih-Lan Hsu and Ming-Yuan Liao

Molecules 2016, 21(4), 513; https://doi.org/10.3390/molecules21040513 - 19 Apr 2016

Cited by 16 | Viewed by 5251

Abstract

Crude extracts of Sedum formosanum N.E.Br. obtained from n-butanol partition (BP) and isopropanol salting-out pretreatment (ISP) were analyzed using antioxidation assays. The results indicated that the extract from ISP contained more potent antioxidants and thus exhibited more antioxidant activity in all the [...] Read more.

Crude extracts of Sedum formosanum N.E.Br. obtained from n-butanol partition (BP) and isopropanol salting-out pretreatment (ISP) were analyzed using antioxidation assays. The results indicated that the extract from ISP contained more potent antioxidants and thus exhibited more antioxidant activity in all the assays. The superoxide radical-scavenging activity and inhibition of nitric oxide radicals achieved after ISP were 3.65 and 2.18 times higher than those achieved through BP, respectively. Eight bioactive natural products were isolated and identified according to an analysis of antioxidation activity in different fractions of the ISP crude extract, namely three cyanophoric glycosides 1–3, three flavonoids 4–6 and two phenolic compounds (7 and a new compound 8). Among them, compounds 5 and 6 exhibit the highest antioxidation capability, and the ISP is suitable for obtaining compounds 5 and 6 using HPLC chromatograms. Therefore, ISP is an excellent extraction technology that can be used to extract antioxidant compounds in the nutraceutical and pharmaceutical industries. Full article

(This article belongs to the Section Natural Products Chemistry)

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15 pages, 3370 KiB

Open AccessArticle

Sulforaphane Analogues with Heterocyclic Moieties: Syntheses and Inhibitory Activities against Cancer Cell Lines

by Ye-Hui Shi, Dong-Fang Dai, Jing Li, Yan-Wei Dong, Yin Jiang, Huan-Gong Li, Yuan Gao, Chuan-Ke Chong, Hui-Ying Li, Xiao-Qian Chu, Cheng Yang, Quan Zhang, Zhong-Sheng Tong, Cui-Gai Bai and Yue Chen

Molecules 2016, 21(4), 514; https://doi.org/10.3390/molecules21040514 - 21 Apr 2016

Cited by 14 | Viewed by 7058

Abstract

Recent studies have shown that sulforaphane (SFN) selectively inhibits the growth of ALDH⁺ breast cancer stem-like cells.Herein, a series of SFN analogues were synthesized and evaluated against breast cancer cell lines MCF-7 and SUM-159, and the leukemia stem cell-like cell line KG-1a. [...] Read more.

Recent studies have shown that sulforaphane (SFN) selectively inhibits the growth of ALDH⁺ breast cancer stem-like cells.Herein, a series of SFN analogues were synthesized and evaluated against breast cancer cell lines MCF-7 and SUM-159, and the leukemia stem cell-like cell line KG-1a. These SFN analogues were characterized by the replacement of the methyl group with heterocyclic moieties, and the replacement of the sulfoxide group with sulfide or sulfone. A growth inhibitory assay indicated that the tetrazole analogs 3d, 8d and 9d were significantly more potent than SFN against the three cancer cell lines. Compound 14c, the water soluble derivative of tetrazole sulfide 3d, demonstrated higher potency against KG-1a cell line than 3d. SFN, 3d and 14c significantly induced the activation of caspase-3, and reduced the ALDH⁺ subpopulation in the SUM159 cell line, while the marketed drug doxrubicin(DOX) increased the ALDH⁺ subpopulation. Full article

(This article belongs to the Collection Heterocyclic Compounds)

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7 pages, 1206 KiB

Open AccessArticle

Two New Bioactive α-Pyrones from Hypericum japonicum

by Linzhen Hu, Zhenzhen Wang, Jinwen Zhang, Yuanyuan Lu, Kaiping Wang, Yongbo Xue, Yu Zhang and Yonghui Zhang

Molecules 2016, 21(4), 515; https://doi.org/10.3390/molecules21040515 - 19 Apr 2016

Cited by 11 | Viewed by 5572

Abstract

Hypericum japonicum (Guttiferae), a type of annual or perennial herb, has been historically applied to cure infectious hepatitis, acute and chronic hepatitis, gastrointestinal disorder, and internal hemorrhage. In our successive studies on the genus Hypericum, two new α-pyrones termed japopyrones A and [...] Read more.

Hypericum japonicum (Guttiferae), a type of annual or perennial herb, has been historically applied to cure infectious hepatitis, acute and chronic hepatitis, gastrointestinal disorder, and internal hemorrhage. In our successive studies on the genus Hypericum, two new α-pyrones termed japopyrones A and B (1 and 2) were isolated from H. japonicum. Their structures and absolute configurations were established by the comprehensive analyses of spectroscopic data, the application of the Single-crystal X-ray diffraction structural analysis, and the experimental electronic circular dichroism (ECD) spectra. Bioactivity screenings suggested that compound 2 possessed the potential inhibition efficacy on lytic replication of Kaposi’s sarcoma associated herpesvirus (KSHV) with an IC₅₀ 29.46 μM and a selective index of higher than 6.79, respectively. Full article

(This article belongs to the Section Natural Products Chemistry)

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11 pages, 1152 KiB

Open AccessArticle

Synthesis and Antitumor Evaluation of Novel 5-Hydrosulfonyl-1H-benzo[d]imidazol-2(3H)-one Derivatives

by Guang Ouyang, Rongsheng Tong, Jinqi Li, Lan Bai, Liang Ouyang, Xingmei Duan, Fengqiong Li, Pin He, Jianyou Shi and Yuxin He

Molecules 2016, 21(4), 516; https://doi.org/10.3390/molecules21040516 - 20 Apr 2016

Cited by 6 | Viewed by 6234

Abstract

A series of novel 5-hydrosulfonyl-1H-benzo[d]imidazol-2(3H)-one derivatives bearing natural product substructures has been successfully synthesized and their antitumor activity studied. These newly synthesized derivatives were characterized by ¹H-NMR, ¹³C-NMR and high resolution mass spectral data, then [...] Read more.

A series of novel 5-hydrosulfonyl-1H-benzo[d]imidazol-2(3H)-one derivatives bearing natural product substructures has been successfully synthesized and their antitumor activity studied. These newly synthesized derivatives were characterized by ¹H-NMR, ¹³C-NMR and high resolution mass spectral data, then screened as antitumor agents against the A549, HCC1937, and MDA-MB-468 human tumor cell lines using MTT cell proliferation assays. The results show that some of these compounds can effectively inhibit the growth of these cancerous cells, with compound 5b being the best one (IC₅₀ = 2.6 μM). Flow cytometry data revealed that compound 5b induced apoptosis of HCC1937 cells with increased solution concentration. The structure and activity relationships (SAR) of these compounds is summarized. 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, 1443 KiB

Open AccessCommunication

A Chemo-Enzymatic Road Map to the Synthesis of CoA Esters

by Dominik M. Peter, Bastian Vögeli, Niña Socorro Cortina and Tobias J. Erb

Molecules 2016, 21(4), 517; https://doi.org/10.3390/molecules21040517 - 20 Apr 2016

Cited by 60 | Viewed by 16946

Abstract

Coenzyme A (CoA) is a ubiquitous cofactor present in every known organism. The thioesters of CoA are core intermediates in many metabolic processes, such as the citric acid cycle, fatty acid biosynthesis and secondary metabolism, including polyketide biosynthesis. Synthesis of CoA-thioesters is [...] Read more.

Coenzyme A (CoA) is a ubiquitous cofactor present in every known organism. The thioesters of CoA are core intermediates in many metabolic processes, such as the citric acid cycle, fatty acid biosynthesis and secondary metabolism, including polyketide biosynthesis. Synthesis of CoA-thioesters is vital for the study of CoA-dependent enzymes and pathways, but also as standards for metabolomics studies. In this work we systematically tested five chemo-enzymatic methods for the synthesis of the three most abundant acyl-CoA thioester classes in biology; saturated acyl-CoAs, α,β-unsaturated acyl-CoAs (i.e., enoyl-CoA derivatives), and α-carboxylated acyl-CoAs (i.e., malonyl-CoA derivatives). Additionally we report on the substrate promiscuity of three newly described acyl-CoA dehydrogenases that allow the simple conversion of acyl-CoAs into enoyl-CoAs. With these five methods, we synthesized 26 different CoA-thioesters with a yield of 40% or higher. The CoA esters produced range from short- to long-chain, include branched and α,β-unsaturated representatives as well as other functional groups. Based on our results we provide a general guideline to the optimal synthesis method of a given CoA-thioester in respect to its functional group(s) and the commercial availability of the precursor molecule. The proposed synthetic routes can be performed in small scale and do not require special chemical equipment, making them convenient also for biological laboratories. Full article

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

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21 pages, 9278 KiB

Open AccessArticle

Anti-Inflammatory Activities of Pentaherbs Formula, Berberine, Gallic Acid and Chlorogenic Acid in Atopic Dermatitis-Like Skin Inflammation

by Miranda S. M. Tsang, Delong Jiao, Ben C. L. Chan, Kam-Lun Hon, Ping C. Leung, Clara B. S. Lau, Eric C. W. Wong, Ling Cheng, Carmen K. M. Chan, Christopher W. K. Lam and Chun K. Wong

Molecules 2016, 21(4), 519; https://doi.org/10.3390/molecules21040519 - 20 Apr 2016

Cited by 124 | Viewed by 17202

Abstract

Atopic dermatitis (AD) is a common allergic skin disease, characterized by dryness, itchiness, thickening and inflammation of the skin. Infiltration of eosinophils into the dermal layer and presence of edema are typical characteristics in the skin biopsy of AD patients. Previous in vitro [...] Read more.

Atopic dermatitis (AD) is a common allergic skin disease, characterized by dryness, itchiness, thickening and inflammation of the skin. Infiltration of eosinophils into the dermal layer and presence of edema are typical characteristics in the skin biopsy of AD patients. Previous in vitro and clinical studies showed that the Pentaherbs formula (PHF) consisting of five traditional Chinese herbal medicines, Flos Lonicerae, Herba Menthae, Cortex Phellodendri, Cortex Moutan and Rhizoma Atractylodis at w/w ratio of 2:1:2:2:2 exhibited therapeutic potential in treating AD. In this study, an in vivo murine model with oxazolone (OXA)-mediated dermatitis was used to elucidate the efficacy of PHF. Active ingredients of PHF water extract were also identified and quantified, and their in vitro anti-inflammatory activities on pruritogenic cytokine IL-31- and alarmin IL-33-activated human eosinophils and dermal fibroblasts were evaluated. Ear swelling, epidermis thickening and eosinophils infiltration in epidermal and dermal layers, and the release of serum IL-12 of the murine OXA-mediated dermatitis were significantly reduced upon oral or topical treatment with PHF (all p < 0.05). Gallic acid, chlorogenic acid and berberine contents (w/w) in PHF were found to be 0.479%, 1.201% and 0.022%, respectively. Gallic acid and chlorogenic acid could suppress the release of pro-inflammatory cytokine IL-6 and chemokine CCL7 and CXCL8, respectively, in IL-31- and IL-33-treated eosinophils-dermal fibroblasts co-culture; while berberine could suppress the release of IL-6, CXCL8, CCL2 and CCL7 in the eosinophil culture and eosinophils-dermal fibroblasts co-culture (all p < 0.05). These findings suggest that PHF can ameliorate allergic inflammation and attenuate the activation of eosinophils. Full article

(This article belongs to the Collection Herbal Medicine Research)

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14 pages, 5351 KiB

Open AccessArticle

Antimicrobial Lemongrass Essential Oil—Copper Ferrite Cellulose Acetate Nanocapsules

by Ioannis L. Liakos, Mohamed H. Abdellatif, Claudia Innocenti, Alice Scarpellini, Riccardo Carzino, Virgilio Brunetti, Sergio Marras, Rosaria Brescia, Filippo Drago and Pier Paolo Pompa

Molecules 2016, 21(4), 520; https://doi.org/10.3390/molecules21040520 - 20 Apr 2016

Cited by 29 | Viewed by 9222

Abstract

Cellulose acetate (CA) nanoparticles were combined with two antimicrobial agents, namely lemongrass (LG) essential oil and Cu-ferrite nanoparticles. The preparation method of CA nanocapsules (NCs), with the two antimicrobial agents, was based on the nanoprecipitation method using the solvent/anti-solvent technique. Several physical and [...] Read more.

Cellulose acetate (CA) nanoparticles were combined with two antimicrobial agents, namely lemongrass (LG) essential oil and Cu-ferrite nanoparticles. The preparation method of CA nanocapsules (NCs), with the two antimicrobial agents, was based on the nanoprecipitation method using the solvent/anti-solvent technique. Several physical and chemical analyses were performed to characterize the resulting NCs and to study their formation mechanism. The size of the combined antimicrobial NCs was found to be ca. 220 nm. The presence of Cu-ferrites enhanced the attachment of LG essential oil into the CA matrix. The magnetic properties of the combined construct were weak, due to the shielding of Cu-ferrites from the polymeric matrix, making them available for drug delivery applications where spontaneous magnetization effects should be avoided. The antimicrobial properties of the NCs were significantly enhanced with respect to CA/LG only. This work opens novel routes for the development of organic/inorganic nanoparticles with exceptional antimicrobial activities. Full article

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

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11 pages, 1390 KiB

Open AccessArticle

Sorption Kinetics on Open Carbon Nanohorn Aggregates: The Effect of Molecular Diameter

by Brice A. Russell, Pravin Khanal, Maria M. Calbi, Masako Yudasaka, Sumio Iijima and Aldo D. Migone

Molecules 2016, 21(4), 521; https://doi.org/10.3390/molecules21040521 - 21 Apr 2016

Cited by 7 | Viewed by 5605

Abstract

We present the results of a study of the kinetics of adsorption on aggregates of open carbon nanohorns using argon and CF₄ sorbates. We measured the equilibration times for each value of the sorbent loading along eight adsorption isotherms (four isotherms for [...] Read more.

We present the results of a study of the kinetics of adsorption on aggregates of open carbon nanohorns using argon and CF₄ sorbates. We measured the equilibration times for each value of the sorbent loading along eight adsorption isotherms (four isotherms for each sorbate species). We found that: the equilibration times decrease as the sorbent loading (and the equilibrium pressure of the coexisting gas) increases, for a given temperature; and, that, for a given value of the sorbent loading, the equilibration times decrease with increasing temperature. When considering the effect of scaling of the temperatures by the respective critical temperatures we found that, at the same scaled temperature and at comparable loadings, the equilibration times for CF₄ were longer than those for argon. We discuss a possible explanation for this result. Full article

(This article belongs to the Special Issue Carbon Nanotubes: Advances and Applications)

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16 pages, 3153 KiB

Open AccessArticle

Delivery of Gemcitabine Prodrugs Employing Mesoporous Silica Nanoparticles

by Alessio Malfanti, Ivana Miletto, Emanuela Bottinelli, Daniele Zonari, Giulia Blandino, Gloria Berlier and Silvia Arpicco

Molecules 2016, 21(4), 522; https://doi.org/10.3390/molecules21040522 - 21 Apr 2016

Cited by 35 | Viewed by 8145

Abstract

In this paper, mesoporous silica nanoparticles (MSNs) were studied as vehicles for the delivery of the antitumoral drug gemcitabine (GEM) and of its 4-(N)-acyl derivatives, (4-(N)-valeroyl-(C5GEM), 4-(N)-lauroyl-(C12GEM) and 4-(N)-stearoyl-gemcitabine (C18GEM)). The loading of the GEM [...] Read more.

In this paper, mesoporous silica nanoparticles (MSNs) were studied as vehicles for the delivery of the antitumoral drug gemcitabine (GEM) and of its 4-(N)-acyl derivatives, (4-(N)-valeroyl-(C5GEM), 4-(N)-lauroyl-(C12GEM) and 4-(N)-stearoyl-gemcitabine (C18GEM)). The loading of the GEM lipophilic prodrugs on MSNs was explored with the aim to obtain both a physical and a chemical protection of GEM from rapid plasmatic metabolization. For this purpose, MSNs as such or with grafted aminopropyl and carboxyethyl groups were prepared and characterized. Then, their different drug loading capacity in relation to the nature of the functional group was evaluated. In our experimental conditions, GEM was not loaded in any MSNs, while C12GEM was the most efficiently encapsulated and employed for further evaluation. The results showed that loading capacity increased with the presence of functional groups on the nanoparticles; similarly, the presence of functional groups on MSNs’ surface influenced the drug release profile. Finally, the cytotoxicity of the different preparations was evaluated and data showed that C12GEM loaded MSNs are less cytotoxic than the free drug with an activity that increased with the incubating time, indicating that all these systems are able to release the drug in a controlled manner. Altogether, the results demonstrate that these MSNs could be an interesting system for the delivery of anticancer drugs. 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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10 pages, 2467 KiB

Open AccessArticle

Glycyrrhetic Acid Ameliorates Dextran Sulfate Sodium-Induced Ulcerative Colitis in Vivo

by Yong-Deok Jeon, Sa-Haeng Kang, Keuk-Soo Bang, Young-Nam Chang, Jong-Hyun Lee and Jong-Sik Jin

Molecules 2016, 21(4), 523; https://doi.org/10.3390/molecules21040523 - 22 Apr 2016

Cited by 31 | Viewed by 7342

Abstract

Glycyrrhizae Radix (GR) is a Korean traditional herb medicine that is widely used in clinical health care. Glycyrrhetic acid (GA) is an aglycone saponin extracted from GR that has anti-inflammatory, anti-cancer, and anti-viral effects. However, the anti-inflammatory effects of GA in colitis have [...] Read more.

Glycyrrhizae Radix (GR) is a Korean traditional herb medicine that is widely used in clinical health care. Glycyrrhetic acid (GA) is an aglycone saponin extracted from GR that has anti-inflammatory, anti-cancer, and anti-viral effects. However, the anti-inflammatory effects of GA in colitis have not been reported. This study investigated the role of GA on ulcerative colitis in a dextran sulfate sodium (DSS)-induced mouse colitis model. DSS-treated mice displayed weight loss and shortened colon length compared with control mice. Mice administered GA showed less weight loss and longer colon length than the DSS-treated group. Interleukin (IL)-6, IL-1β, and tumor necrosis factor-alpha were decreased by GA treatment. GA treatment also reduced DSS-induced microscopic damage to colon tissue. GA regulates the phosphorylation of transcription factors including nuclear factor-kappa B (NF-κB) and IκB alpha, and regulates the expression of cycloxygenase-2 and prostaglandin E₂. GA thus showed beneficial effects in a mouse model of colitis, implicating GA might be a useful herb-derived medicine in the treatment of ulcerative colitis. Full article

(This article belongs to the Section Natural Products Chemistry)

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15 pages, 1737 KiB

Open AccessArticle

The Effects of Fungicide, Soil Fumigant, Bio-Organic Fertilizer and Their Combined Application on Chrysanthemum Fusarium Wilt Controlling, Soil Enzyme Activities and Microbial Properties

by Shuang Zhao, Xi Chen, Shiping Deng, Xuena Dong, Aiping Song, Jianjun Yao, Weimin Fang and Fadi Chen

Molecules 2016, 21(4), 526; https://doi.org/10.3390/molecules21040526 - 21 Apr 2016

Cited by 56 | Viewed by 8302

Abstract

Sustained monoculture often leads to a decline in soil quality, in particular to the build-up of pathogen populations, a problem that is conventionally addressed by the use of either fungicide and/or soil fumigation. This practice is no longer considered to be either environmentally [...] Read more.

Sustained monoculture often leads to a decline in soil quality, in particular to the build-up of pathogen populations, a problem that is conventionally addressed by the use of either fungicide and/or soil fumigation. This practice is no longer considered to be either environmentally sustainable or safe. While the application of organic fertilizer is seen as a means of combating declining soil fertility, it has also been suggested as providing some control over certain soil-borne plant pathogens. Here, a greenhouse comparison was made of the Fusarium wilt control efficacy of various treatments given to a soil in which chrysanthemum had been produced continuously for many years. The treatments comprised the fungicide carbendazim (MBC), the soil fumigant dazomet (DAZ), the incorporation of a Paenibacillus polymyxa SQR21 (P. polymyxa SQR21, fungal antagonist) enhanced bio-organic fertilizer (BOF), and applications of BOF combined with either MBC or DAZ. Data suggest that all the treatments evaluated show good control over Fusarium wilt. The MBC and DAZ treatments were effective in suppressing the disease, but led to significant decrease in urease activity and no enhancement of catalase activity in the rhizosphere soils. BOF including treatments showed significant enhancement in soil enzyme activities and microbial communities compared to the MBC and DAZ, evidenced by differences in bacterial/fungi (B/F) ratios, Shannon–Wiener indexes and urease, catalase and sucrase activities in the rhizosphere soil of chrysanthemum. Of all the treatments evaluated, DAZ/BOF application not only greatly suppressed Fusarium wilt and enhanced soil enzyme activities and microbial communities but also promoted the quality of chrysanthemum obviously. Our findings suggest that combined BOF with DAZ could more effectively control Fusarium wilt disease of chrysanthemum. Full article

(This article belongs to the Section Molecular Diversity)

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18 pages, 7781 KiB

Open AccessArticle

The Effects of Topical Application of Polycal (a 2:98 (g/g) Mixture of Polycan and Calcium Gluconate) on Experimental Periodontitis and Alveolar Bone Loss in Rats

by Sang-In Park, Su-Jin Kang, Chang-Hyun Han, Joo-Wan Kim, Chang-Hyun Song, Sang-Nam Lee, Sae-Kwang Ku and Young-Joon Lee

Molecules 2016, 21(4), 527; https://doi.org/10.3390/molecules21040527 - 22 Apr 2016

Cited by 16 | Viewed by 6078

Abstract

The aim of this study was to observe whether Polycal has inhibitory activity on ligation-induced experimental periodontitis and related alveolar bone loss in rats following topical application to the gingival regions. One day after the ligation placements, Polycal (50, 25, and 12.5 mg/mL [...] Read more.

The aim of this study was to observe whether Polycal has inhibitory activity on ligation-induced experimental periodontitis and related alveolar bone loss in rats following topical application to the gingival regions. One day after the ligation placements, Polycal (50, 25, and 12.5 mg/mL solutions at 200 μL/rat) was topically applied to the ligated gingival regions daily for 10 days. Changes in bodyweight, alveolar bone loss index, and total number of buccal gingival aerobic bacterial cells were monitored, and the anti-inflammatory effects were investigated via myeloperoxidase activity and levels of the pro-inflammatory cytokines IL-1β and TNF-α. The activities of inducible nitric oxide synthase (iNOS) and lipid peroxidation (MDA) were also evaluated. Bacterial proliferation, periodontitis, and alveolar bone loss induced by ligature placements were significantly inhibited after 10 days of continuous topical application of Polycal. These results indicate that topical application of Polycal has a significant inhibitory effect on periodontitis and related alveolar bone loss in rats mediated by antibacterial, anti-inflammatory, and anti-oxidative activities. Full article

(This article belongs to the Section Medicinal Chemistry)

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13 pages, 2560 KiB

Open AccessArticle

Enantioselective Separation of 4,8-DHT and Phytotoxicity of the Enantiomers on Various Plant Species

by Li Yang, Xiao-Yan Ma, Xiao Ruan, De-An Jiang, Cun-De Pan and Qiang Wang

Molecules 2016, 21(4), 528; https://doi.org/10.3390/molecules21040528 - 22 Apr 2016

Cited by 7 | Viewed by 5432

Abstract

As a candidate for bioherbicide, 4,8-dihydroxy-1-tetralone (4,8-DHT) was isolated from Caryospora callicarpa epicarp and its two enantiomers, S-(+)-isosclerone and R-(−)-regiolone, were separated by chiral high-performance liquid chromatography (HPLC) on a Chiralcel OD column with chiral stationary phase (CSP)-coated cellulose-tris(3,5-dimethylphenylcarbamate). Then, the [...] Read more.

As a candidate for bioherbicide, 4,8-dihydroxy-1-tetralone (4,8-DHT) was isolated from Caryospora callicarpa epicarp and its two enantiomers, S-(+)-isosclerone and R-(−)-regiolone, were separated by chiral high-performance liquid chromatography (HPLC) on a Chiralcel OD column with chiral stationary phase (CSP)-coated cellulose-tris(3,5-dimethylphenylcarbamate). Then, the phytotoxicity of 4,8-DHT and its enantiomers toward the seeds germination and seedling growth of the five tested plant species, including lettuce (Latuca sativa), radish (Raphanus sativus), cucumber (Cucumis sativus), onion (Allium cepa), and wheat (Triticum aestivum), were investigated and the results indicated a hormesis at low concentration of 4,8-DHT and its enantiomers, but a retardant effect at high concentration. Between the two enantiomers of 4,8-DHT, the S-(+)-isosclerone was more toxic to seeds germination and seedling growth of the five tested plant species than the R-(−)-regiolone, and also the phytotoxicity of S-(+)-isosclerone varied with different plants. For example, S-(+)-isosclerone was the most active to seedling growth of lettuce, indicating that S-(+)-isosclerone had specific effects on different organisms. Thus, all of the chirality and concentration of 4,8-DHT, as well as the affected plant species, need to be taken into consideration in the development and utilization of 4,8-DHT. Full article

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10 pages, 1187 KiB

Open AccessArticle

Volatile Organic Compounds Emissions from Luculia pinceana Flower and Its Changes at Different Stages of Flower Development

by Yuying Li, Hong Ma, Youming Wan, Taiqiang Li, Xiuxian Liu, Zhenghai Sun and Zhenghong Li

Molecules 2016, 21(4), 531; https://doi.org/10.3390/molecules21040531 - 22 Apr 2016

Cited by 37 | Viewed by 8936

Abstract

Luculia plants are famed ornamental plants with sweetly fragrant flowers, of which L. pinceana Hooker, found primarily in Yunnan Province, China, has the widest distribution. Solid phase microextraction-gas chromatography-mass spectrometry (SPME-GC-MS) was employed to identify the volatile organic compounds (VOCs) emitted from different [...] Read more.

Luculia plants are famed ornamental plants with sweetly fragrant flowers, of which L. pinceana Hooker, found primarily in Yunnan Province, China, has the widest distribution. Solid phase microextraction-gas chromatography-mass spectrometry (SPME-GC-MS) was employed to identify the volatile organic compounds (VOCs) emitted from different flower development stages of L. pinceana for the evaluation of floral volatile polymorphism. Peak areas were normalized as percentages and used to determine the relative amounts of the volatiles. The results showed that a total of 39 compounds were identified at four different stages of L. pinceana flower development, including 26 at the bud stage, 26 at the initial-flowering stage, 32 at the full-flowering stage, and 32 at the end-flowering stage. The most abundant compound was paeonol (51%–83%) followed by (E,E)-α-farnesene, cyclosativene, and δ-cadinene. All these volatile compounds create the unique fragrance of L. pinceana flower. Floral scent emission offered tendency of ascending first and descending in succession, meeting its peak level at the initial-flowering stage. The richest diversity of floral volatile was detected at the third and later periods of flower development. Principal component analysis (PCA) indicated that the composition and its relative content of floral scent differed throughout the whole flower development. The result has important implications for future floral fragrance breeding of Luculia. L. pinceana would be adequate for a beneficial houseplant and has a promising prospect for development as essential oil besides for a fragrant ornamental owing to the main compounds of floral scent with many medicinal properties. Full article

(This article belongs to the Section Natural Products Chemistry)

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18 pages, 4856 KiB

Open AccessArticle

Identification of Subnanometric Ag Species, Their Interaction with Supports and Role in Catalytic CO Oxidation

by Yulia Kotolevich, Ekaterina Kolobova, Evgeniy Khramov, Jesús Efren Cabrera Ortega, Mario H. Farías, Yan Zubavichus, Rodolfo Zanella, Josué D. Mota-Morales, Alexey Pestryakov, Nina Bogdanchikova and Vicente Cortés Corberán

Molecules 2016, 21(4), 532; https://doi.org/10.3390/molecules21040532 - 22 Apr 2016

Cited by 14 | Viewed by 5816

Abstract

The nature and size of the real active species of nanoparticulated metal supported catalysts is still an unresolved question. The technique of choice to measure particle sizes at the nanoscale, HRTEM, has a practical limit of 1 nm. This work is aimed to [...] Read more.

The nature and size of the real active species of nanoparticulated metal supported catalysts is still an unresolved question. The technique of choice to measure particle sizes at the nanoscale, HRTEM, has a practical limit of 1 nm. This work is aimed to identify the catalytic role of subnanometer species and methods to detect and characterize them. In this frame, we investigated the sensitivity to redox pretreatments of Ag/Fe/TiO₂, Ag/Mg/TiO₂ and Ag/Ce/TiO₂ catalysts in CO oxidation. The joint application of HRTEM, SR-XRD, DRS, XPS, EXAFS and XANES methods indicated that most of the silver in all samples is in the form of Ag species with size <1 nm. The differences in catalytic properties and sensitivity to pretreatments, observed for the studied Ag catalysts, could not be explained taking into account only the Ag particles whose size distribution is measured by HRTEM, but may be explained by the presence of the subnanometer Ag species, undetectable by HRTEM, and their interaction with supports. This result highlights their role as active species and the need to take them into account to understand integrally the catalysis by supported nanometals. Full article

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

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7 pages, 390 KiB

Open AccessArticle

Repellent Activity of the Essential Oil from the Heartwood of Pilgerodendron uviferum (D. Don) Florin against Aegorhinus superciliosus (Coleoptera: Curculionidae)

by Javier Espinoza, Alejandro Urzúa, Jocelyne Tampe, Leonardo Parra and Andrés Quiroz

Molecules 2016, 21(4), 533; https://doi.org/10.3390/molecules21040533 - 22 Apr 2016

Cited by 11 | Viewed by 6064

Abstract

The weevil Aegorhinus superciliosus Guérin (Coleoptera: Curculionidae), which is endemic to Central-Southern Chile and Argentina, is one of the major berry pests in Chile and the most important pest in the La Araucanía Region (38°44′9″S, 72°35′25″W). Due to the poor effectiveness and problems [...] Read more.

The weevil Aegorhinus superciliosus Guérin (Coleoptera: Curculionidae), which is endemic to Central-Southern Chile and Argentina, is one of the major berry pests in Chile and the most important pest in the La Araucanía Region (38°44′9″S, 72°35′25″W). Due to the poor effectiveness and problems surrounding the implementation of the traditional control methods using organophosphate and carbamate insecticides, new strategies for controlling this pest are needed. In this communication, we evaluated the behavioral responses of male and female A. superciliosus to volatile compounds released from the essential oil (EO) obtained from the heartwood of Pilgerodendron uviferum (D. Don) Florin using olfactometric bioassays. The composition of the EO was analyzed using gas chromatography (GC) and gas chromatography/mass spectrometry (GC/MS). According to these analyses, δ-cadinol (24.16%), cubenol (22.64%), 15-copaenol (15.46%) and δ-cadinene (10.81%) were the principal components of the EO. The Pilgerodendron uviferum EO, which is almost exclusively composed of sesquiterpenes (99.5%), exhibited a repellent effect against A. superciliosus adults, regardless of the sex or concentration used (56.6 mg/cm³ and 1.58 × 10⁻² mg/cm³). The EO has low volatility and greater persistence than the EOs composed of monoterpenes and is considered a good model in the search for raspberry weevil repellents. Full article

(This article belongs to the Collection Bioactive Compounds)

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13 pages, 2694 KiB

Open AccessArticle

Peruvoside, a Cardiac Glycoside, Induces Primitive Myeloid Leukemia Cell Death

by Qian Feng, Wa Seng Leong, Liang Liu and Wai-In Chan

Molecules 2016, 21(4), 534; https://doi.org/10.3390/molecules21040534 - 22 Apr 2016

Cited by 28 | Viewed by 7210

Abstract

Despite the available chemotherapy and treatment, leukemia remains a difficult disease to cure due to frequent relapses after treatment. Among the heterogeneous leukemic cells, a rare population referred as the leukemic stem cell (LSC), is thought to be responsible for relapses and drug [...] Read more.

Despite the available chemotherapy and treatment, leukemia remains a difficult disease to cure due to frequent relapses after treatment. Among the heterogeneous leukemic cells, a rare population referred as the leukemic stem cell (LSC), is thought to be responsible for relapses and drug resistance. Cardiac glycosides (CGs) have been used in treating heart failure despite its toxicity. Recently, increasing evidence has demonstrated its new usage as a potential anti-cancer drug. Ouabain, one of the CGs, specifically targeted CD34⁺CD38⁻ leukemic stem-like cells, but not the more mature CD34⁺CD38⁺ leukemic cells, making this type of compounds a potential treatment for leukemia. In search of other potential anti-leukemia CGs, we found that Peruvoside, a less studied CG, is more effective than Ouabain and Digitoxin at inducing cell death in primitive myeloid leukemia cells without obvious cytotoxicity on normal blood cells. Similar to Ouabain and Digitoxin, Peruvoside also caused cell cycle arrest at G₂/M stage. It up-regulates CDKN1A expression and activated the cleavage of Caspase 3, 8 and PARP, resulting in apoptosis. Thus, Peruvoside showed potent anti-leukemia effect, which may serve as a new anti-leukemia agent in the future. Full article

(This article belongs to the Section Natural Products Chemistry)

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14 pages, 5708 KiB

Open AccessArticle

Breast Cancer Stem Cell Culture and Enrichment Using Poly(ε-Caprolactone) Scaffolds

by Sònia Palomeras, Marc Rabionet, Inés Ferrer, Ariadna Sarrats, Maria Luisa Garcia-Romeu, Teresa Puig and Joaquim Ciurana

Molecules 2016, 21(4), 537; https://doi.org/10.3390/molecules21040537 - 23 Apr 2016

Cited by 39 | Viewed by 10431

Abstract

The cancer stem cell (CSC) population displays self-renewal capabilities, resistance to conventional therapies, and a tendency to post-treatment recurrence. Increasing knowledge about CSCs’ phenotype and functions is needed to investigate new therapeutic strategies against the CSC population. Here, poly(ε-caprolactone) (PCL), a biocompatible polymer [...] Read more.

The cancer stem cell (CSC) population displays self-renewal capabilities, resistance to conventional therapies, and a tendency to post-treatment recurrence. Increasing knowledge about CSCs’ phenotype and functions is needed to investigate new therapeutic strategies against the CSC population. Here, poly(ε-caprolactone) (PCL), a biocompatible polymer free of toxic dye, has been used to fabricate scaffolds, solid structures suitable for 3D cancer cell culture. It has been reported that scaffold cell culture enhances the CSCs population. A RepRap BCN3D+ printer and 3 mm PCL wire were used to fabricate circular scaffolds. PCL design and fabrication parameters were first determined and then optimized considering several measurable variables of the resulting scaffolds. MCF7 breast carcinoma cell line was used to assess scaffolds adequacy for 3D cell culture. To evaluate CSC enrichment, the Mammosphere Forming Index (MFI) was performed in 2D and 3D MCF7 cultures. Results showed that the 60° scaffolds were more suitable for 3D culture than the 45° and 90° ones. Moreover, 3D culture experiments, in adherent and non-adherent conditions, showed a significant increase in MFI compared to 2D cultures (control). Thus, 3D cell culture with PCL scaffolds could be useful to improve cancer cell culture and enrich the CSCs population. Full article

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

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13 pages, 2275 KiB

Open AccessArticle

3,5,6,7,8,3′,4′-Heptamethoxyflavone, a Citrus Flavonoid, Ameliorates Corticosterone-Induced Depression-like Behavior and Restores Brain-Derived Neurotrophic Factor Expression, Neurogenesis, and Neuroplasticity in the Hippocampus

by Atsushi Sawamoto, Satoshi Okuyama, Kana Yamamoto, Yoshiaki Amakura, Morio Yoshimura, Mitsunari Nakajima and Yoshiko Furukawa

Molecules 2016, 21(4), 541; https://doi.org/10.3390/molecules21040541 - 23 Apr 2016

Cited by 59 | Viewed by 9444

Abstract

We previously reported that the citrus flavonoid 3,5,6,7,8,3′,4′-heptamethoxyflavone (HMF) increased the expression of brain-derived neurotrophic factor (BDNF) in the hippocampus of a transient global ischemia mouse model. Since the BDNF hypothesis of depression postulates that a reduction in BDNF is directly involved in [...] Read more.

We previously reported that the citrus flavonoid 3,5,6,7,8,3′,4′-heptamethoxyflavone (HMF) increased the expression of brain-derived neurotrophic factor (BDNF) in the hippocampus of a transient global ischemia mouse model. Since the BDNF hypothesis of depression postulates that a reduction in BDNF is directly involved in the pathophysiology of depression, we evaluated the anti-depressive effects of HMF in mice with subcutaneously administered corticosterone at a dose of 20 mg/kg/day for 25 days. We demonstrated that the HMF treatment ameliorated (1) corticosterone-induced body weight loss, (2) corticosterone-induced depression-like behavior, and (3) corticosterone-induced reductions in BDNF production in the hippocampus. We also showed that the HMF treatment restored (4) corticosterone-induced reductions in neurogenesis in the dentate gyrus subgranular zone and (5) corticosterone-induced reductions in the expression levels of phosphorylated calcium-calmodulin-dependent protein kinase II and extracellular signal-regulated kinase1/2. These results suggest that HMF exerts its effects as an anti-depressant drug by inducing the expression of BDNF. Full article

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

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10 pages, 2036 KiB

Open AccessArticle

Highly Efficient Reproducible Perovskite Solar Cells Prepared by Low-Temperature Processing

by Hao Hu, Ka Kan Wong, Tom Kollek, Fabian Hanusch, Sebastian Polarz, Pablo Docampo and Lukas Schmidt-Mende

Molecules 2016, 21(4), 542; https://doi.org/10.3390/molecules21040542 - 23 Apr 2016

Cited by 22 | Viewed by 10339

Abstract

In this work, we describe the role of the different layers in perovskite solar cells to achieve reproducible, ~16% efficient perovskite solar cells. We used a planar device architecture with PEDOT:PSS on the bottom, followed by the perovskite layer and an evaporated C [...] Read more.

In this work, we describe the role of the different layers in perovskite solar cells to achieve reproducible, ~16% efficient perovskite solar cells. We used a planar device architecture with PEDOT:PSS on the bottom, followed by the perovskite layer and an evaporated C₆₀ layer before deposition of the top electrode. No high temperature annealing step is needed, which also allows processing on flexible plastic substrates. Only the optimization of all of these layers leads to highly efficient and reproducible results. In this work, we describe the effects of different processing conditions, especially the influence of the C₆₀ top layer on the device performance. Full article

(This article belongs to the Special Issue Perovskite Solar Cells)

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10 pages, 3082 KiB

Open AccessArticle

Crystallization of Esomeprazole Magnesium Water/Butanol Solvate

by Jenna Skieneh, Bahareh Khalili Najafabadi, Stephen Horne and Sohrab Rohani

Molecules 2016, 21(4), 544; https://doi.org/10.3390/molecules21040544 - 23 Apr 2016

Cited by 12 | Viewed by 11378

Abstract

The molecular structure of esomeprazole magnesium derivative in the solid-state is reported for the first time, along with a simplified crystallization pathway. The structure was determined using the single crystal X-ray diffraction technique to reveal the bonding relationships between esomeprazole heteroatoms and magnesium. [...] Read more.

The molecular structure of esomeprazole magnesium derivative in the solid-state is reported for the first time, along with a simplified crystallization pathway. The structure was determined using the single crystal X-ray diffraction technique to reveal the bonding relationships between esomeprazole heteroatoms and magnesium. The esomeprazole crystallization process was carried out in 1-butanol and water was utilized as anti-solvent. The product proved to be esomeprazole magnesium tetrahydrate with two 1-butanol molecules that crystallized in P6₃ space group, in a hexagonal unit cell. Complete characterization of a sample after drying was conducted by the use of powder X-ray diffraction (PXRD), ¹H-nuclear magnetic resonance (NMR), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), infrared spectroscopy (IR), and dynamic vapor sorption (DVS). Investigation by ¹H-NMR and TGA has shown that the solvent content in the dried sample consists of two water molecules and 0.3 butanol molecules per esomeprazole magnesium molecule. This is different from the single crystal X-ray diffraction results and can be attributed to the loss of some water and 1-butanol molecules stabilized by intermolecular interactions. The title compound, after drying, is a true solvate in terms of water; conversely, 1-butanol fills the voids of the crystal lattice in non-stoichiometric amounts. Full article

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

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Jump to: Editorial, Research, Other

19 pages, 2378 KiB

Open AccessReview

The Current Case of Quinolones: Synthetic Approaches and Antibacterial Activity

by Abdul Naeem, Syed Lal Badshah, Mairman Muska, Nasir Ahmad and Khalid Khan

Molecules 2016, 21(4), 268; https://doi.org/10.3390/molecules21040268 - 28 Mar 2016

Cited by 182 | Viewed by 21303

Abstract

Quinolones are broad-spectrum synthetic antibacterial drugs first obtained during the synthesis of chloroquine. Nalidixic acid, the prototype of quinolones, first became available for clinical consumption in 1962 and was used mainly for urinary tract infections caused by Escherichia coli and other pathogenic Gram-negative [...] Read more.

Quinolones are broad-spectrum synthetic antibacterial drugs first obtained during the synthesis of chloroquine. Nalidixic acid, the prototype of quinolones, first became available for clinical consumption in 1962 and was used mainly for urinary tract infections caused by Escherichia coli and other pathogenic Gram-negative bacteria. Recently, significant work has been carried out to synthesize novel quinolone analogues with enhanced activity and potential usage for the treatment of different bacterial diseases. These novel analogues are made by substitution at different sites—the variation at the C-6 and C-8 positions gives more effective drugs. Substitution of a fluorine atom at the C-6 position produces fluroquinolones, which account for a large proportion of the quinolones in clinical use. Among others, substitution of piperazine or methylpiperazine, pyrrolidinyl and piperidinyl rings also yields effective analogues. A total of twenty six analogues are reported in this review. The targets of quinolones are two bacterial enzymes of the class II topoisomerase family, namely gyrase and topoisomerase IV. Quinolones increase the concentration of drug-enzyme-DNA cleavage complexes and convert them into cellular toxins; as a result they are bactericidal. High bioavailability, relative low toxicity and favorable pharmacokinetics have resulted in the clinical success of fluoroquinolones and quinolones. Due to these superior properties, quinolones have been extensively utilized and this increased usage has resulted in some quinolone-resistant bacterial strains. Bacteria become resistant to quinolones by three mechanisms: (1) mutation in the target site (gyrase and/or topoisomerase IV) of quinolones; (2) plasmid-mediated resistance; and (3) chromosome-mediated quinolone resistance. In plasmid-mediated resistance, the efflux of quinolones is increased along with a decrease in the interaction of the drug with gyrase (topoisomerase IV). In the case of chromosome-mediated quinolone resistance, there is a decrease in the influx of the drug into the cell. Full article

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

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26 pages, 802 KiB

Open AccessReview

Plectranthus amboinicus (Lour.) Spreng: Botanical, Phytochemical, Pharmacological and Nutritional Significance

by Greetha Arumugam, Mallappa Kumara Swamy and Uma Rani Sinniah

Molecules 2016, 21(4), 369; https://doi.org/10.3390/molecules21040369 - 30 Mar 2016

Cited by 240 | Viewed by 36900

Abstract

Plectranthus amboinicus (Lour.) Spreng. is a perennial herb belonging to the family Lamiaceae which occurs naturally throughout the tropics and warm regions of Africa, Asia and Australia. This herb has therapeutic and nutritional properties attributed to its natural phytochemical compounds which are highly [...] Read more.

Plectranthus amboinicus (Lour.) Spreng. is a perennial herb belonging to the family Lamiaceae which occurs naturally throughout the tropics and warm regions of Africa, Asia and Australia. This herb has therapeutic and nutritional properties attributed to its natural phytochemical compounds which are highly valued in the pharmaceutical industry. Besides, it has horticultural properties due to its aromatic nature and essential oil producing capability. It is widely used in folk medicine to treat conditions like cold, asthma, constipation, headache, cough, fever and skin diseases. The leaves of the plant are often eaten raw or used as flavoring agents, or incorporated as ingredients in the preparation of traditional food. The literature survey revealed the occurrence 76 volatiles and 30 non-volatile compounds belonging to different classes of phytochemicals such as monoterpenoids, diterpenoids, triterpenoids, sesquiterpenoids, phenolics, flavonoids, esters, alcohols and aldehydes. Studies have cited numerous pharmacological properties including antimicrobial, antiinflammatory, antitumor, wound healing, anti-epileptic, larvicidal, antioxidant and analgesic activities. Also, it has been found to be effective against respiratory, cardiovascular, oral, skin, digestive and urinary diseases. Yet, scientific validation of many other traditional uses would be appreciated, mainly to discover and authenticate novel bioactive compounds from this herb. This review article provides comprehensive information on the botany, phytochemistry, pharmacology and nutritional importance of P. amboinicus essential oil and its various solvent extracts. This article allows researchers to further explore the further potential of this multi-utility herb for various biomedical applications. Full article

(This article belongs to the Collection Herbal Medicine Research)

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11 pages, 839 KiB

Open AccessReview

Sinigrin and Its Therapeutic Benefits

by Anisha Mazumder, Anupma Dwivedi and Jeanetta Du Plessis

Molecules 2016, 21(4), 416; https://doi.org/10.3390/molecules21040416 - 29 Mar 2016

Cited by 150 | Viewed by 22132

Abstract

Sinigrin (allyl-glucosinolate or 2-propenyl-glucosinolate) is a natural aliphatic glucosinolate present in plants of the Brassicaceae family, such as broccoli and brussels sprouts, and the seeds of Brassica nigra (mustard seeds) which contain high amounts of sinigrin. Since ancient times, mustard has been used [...] Read more.

Sinigrin (allyl-glucosinolate or 2-propenyl-glucosinolate) is a natural aliphatic glucosinolate present in plants of the Brassicaceae family, such as broccoli and brussels sprouts, and the seeds of Brassica nigra (mustard seeds) which contain high amounts of sinigrin. Since ancient times, mustard has been used by mankind for its culinary, as well as medicinal, properties. It has been systematically described and evaluated in the classical Ayurvedic texts. Studies conducted on the pharmacological activities of sinigrin have revealed anti-cancer, antibacterial, antifungal, antioxidant, anti-inflammatory, wound healing properties and biofumigation. This current review will bring concise information about the known therapeutic activities of sinigrin. However, the information on known biological activities is very limited and, hence, further studies still need to be conducted and its molecular mechanisms also need to be explored. This review on the therapeutic benefits of sinigrin can summarize current knowledge about this unique phytocompounds. Full article

(This article belongs to the Collection Herbal Medicine Research)

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15 pages, 2132 KiB

Open AccessReview

Methods for Improving Aptamer Binding Affinity

by Hijiri Hasegawa, Nasa Savory, Koichi Abe and Kazunori Ikebukuro

Molecules 2016, 21(4), 421; https://doi.org/10.3390/molecules21040421 - 28 Mar 2016

Cited by 206 | Viewed by 16198

Abstract

Aptamers are single stranded oligonucleotides that bind a wide range of biological targets. Although aptamers can be isolated from pools of random sequence oligonucleotides using affinity-based selection, aptamers with high affinities are not always obtained. Therefore, further refinement of aptamers is required to [...] Read more.

Aptamers are single stranded oligonucleotides that bind a wide range of biological targets. Although aptamers can be isolated from pools of random sequence oligonucleotides using affinity-based selection, aptamers with high affinities are not always obtained. Therefore, further refinement of aptamers is required to achieve desired binding affinities. The optimization of primary sequences and stabilization of aptamer conformations are the main approaches to refining the binding properties of aptamers. In particular, sequence optimization using combined in silico sequence recombinations and in vitro functional evaluations is effective for the improvement of binding affinities, however, the binding affinities of aptamers are limited by the low hydrophobicity of nucleic acids. Accordingly, introduction of hydrophobic moieties into aptamers expands the diversity of interactions between aptamers and targets. Moreover, construction of multivalent aptamers by connecting aptamers that recognize distinct epitopes is an attractive approach to substantial increases in binding affinity. In addition, binding affinities can be tuned by optimizing the scaffolds of multivalent constructs. In this review, we summarize the various techniques for improving the binding affinities of aptamers. Full article

(This article belongs to the Special Issue Aptamers: Past, Present, and Future)

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13 pages, 4393 KiB

Open AccessReview

The Psychrotolerant Antarctic Fungus Lecanicillium muscarium CCFEE 5003: A Powerful Producer of Cold-Tolerant Chitinolytic Enzymes

by Massimiliano Fenice

Molecules 2016, 21(4), 447; https://doi.org/10.3390/molecules21040447 - 5 Apr 2016

Cited by 44 | Viewed by 8198

Abstract

Lecanicillium muscarium CCFEE 5003, isolated in Continental Antarctica, is a powerful producer of extracellular cold-tolerant enzymes. Chitin-hydrolyzing enzymes seems to be the principal extracellular catalytic activities of this psychrotolerant fungus. The production of chitinolytic activities is induced by chitin and other polysaccharides and [...] Read more.

Lecanicillium muscarium CCFEE 5003, isolated in Continental Antarctica, is a powerful producer of extracellular cold-tolerant enzymes. Chitin-hydrolyzing enzymes seems to be the principal extracellular catalytic activities of this psychrotolerant fungus. The production of chitinolytic activities is induced by chitin and other polysaccharides and is submitted to catabolite repression. The chitinolytic system of L. muscarium consists of a number of different proteins having various molecular weights and diverse biochemical characteristics, but their most significant trait is the marked cold-tolerance. L. muscarium and selected strains of the biocontrol agent of pathogenic fungi Trichoderma harzianum, have been compared for their ability to produce chitinolytic enzymes at different temperatures. At low temperatures the Antarctic strain was definitely much more efficient. Moreover, the fungus was able to exert a strong mycoparasitic action against various other fungi and oomycetes at low temperatures. The parasitic role of this organism appeared related to the production of cell wall degrading enzymes being the release of extracellular chitinolytic enzymes a key event in the mycoparasitic process. Due to the mentioned characteristics, L. muscarium could have an important role for potential applications such as the degradation of chitin-rich materials at low temperature and the biocontrol of pathogenic organisms in cold environments. For these reasons and in view of future industrial application, the production of chitinolytic enzymes by the Antarctic fungus has been up-scaled and optimised in bench-top bioreactor. Full article

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

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32 pages, 1232 KiB

Open AccessReview

Recent Advances in the Analysis of Phenolic Compounds in Unifloral Honeys

by Marco Ciulu, Nadia Spano, Maria I. Pilo and Gavino Sanna

Molecules 2016, 21(4), 451; https://doi.org/10.3390/molecules21040451 - 8 Apr 2016

Cited by 100 | Viewed by 12567

Abstract

Honey is one of the most renowned natural foods. Its composition is extremely variable, depending on its botanical and geographical origins, and the abundant presence of functional compounds has contributed to the increased worldwide interest is this foodstuff. In particular, great attention has [...] Read more.

Honey is one of the most renowned natural foods. Its composition is extremely variable, depending on its botanical and geographical origins, and the abundant presence of functional compounds has contributed to the increased worldwide interest is this foodstuff. In particular, great attention has been paid by the scientific community towards classes of compounds like phenolic compounds, due to their capability to act as markers of unifloral honey origin. In this contribution the most recent progress in the assessment of new analytical procedures aimed at the definition of the qualitative and quantitative profile of phenolic compounds of honey have been highlighted. A special emphasis has been placed on the innovative aspects concerning the extraction procedures, along with the most recent strategies proposed for the analysis of phenolic compounds. Moreover, the centrality of validation procedures has been claimed and extensively discussed in order to ensure the fitness-for-purpose of the proposed analytical methods. In addition, the exploitation of the phenolic profile as a tool for the classification of the botanical and geographical origin has been described, pointing out the usefulness of chemometrics in the interpretation of data sets originating from the analysis of polyphenols. Finally, recent results in concerning the evaluation of the antioxidant properties of unifloral honeys and the development of new analytical approaches aimed at measuring this parameter have been reviewed. Full article

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

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12 pages, 1238 KiB

Open AccessReview

Navigating the Chemical Space of Multitarget-Directed Ligands: From Hybrids to Fragments in Alzheimer’s Disease

by Federica Prati, Andrea Cavalli and Maria Laura Bolognesi

Molecules 2016, 21(4), 466; https://doi.org/10.3390/molecules21040466 - 8 Apr 2016

Cited by 96 | Viewed by 11771

Abstract

Multitarget drug discovery is one of the hottest topics and most active fields in the search for new molecules against Alzheimer’s disease (AD). Over the last 20 years, many promising multitarget-directed ligands (MTDLs) have been identified and developed at a pre-clinical level. However, [...] Read more.

Multitarget drug discovery is one of the hottest topics and most active fields in the search for new molecules against Alzheimer’s disease (AD). Over the last 20 years, many promising multitarget-directed ligands (MTDLs) have been identified and developed at a pre-clinical level. However, how to design them in a rational way remains the most fundamental challenge of medicinal chemists. This is related to the foundational question of achieving an optimized activity towards multiple targets of interest, while preserving drug-like properties. In this respect, large hybrid molecules and small fragments are poles apart. In this review article, our aim is to appraise what we have accomplished in the development of both hybrid- and fragment-like molecules directed to diverse AD targets (i.e., acetylcholinesterase, NMDA receptors, metal chelation, BACE-1 and GSK-3β). In addition, we attempt to highlight what are the persistent needs that deserve to be improved and cared for, with the ultimate goal of moving an MTDL to AD clinical studies. Full article

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

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21 pages, 4448 KiB

Open AccessReview

Neutral- and Multi-Colored Semitransparent Perovskite Solar Cells

by Kyu-Tae Lee, L. Jay Guo and Hui Joon Park

Molecules 2016, 21(4), 475; https://doi.org/10.3390/molecules21040475 - 11 Apr 2016

Cited by 63 | Viewed by 14409

Abstract

In this review, we summarize recent works on perovskite solar cells with neutral- and multi-colored semitransparency for building-integrated photovoltaics and tandem solar cells. The perovskite solar cells exploiting microstructured arrays of perovskite “islands” and transparent electrodes—the latter of which include thin metallic films, [...] Read more.

In this review, we summarize recent works on perovskite solar cells with neutral- and multi-colored semitransparency for building-integrated photovoltaics and tandem solar cells. The perovskite solar cells exploiting microstructured arrays of perovskite “islands” and transparent electrodes—the latter of which include thin metallic films, metal nanowires, carbon nanotubes, graphenes, and transparent conductive oxides for achieving optical transparency—are investigated. Moreover, the perovskite solar cells with distinctive color generation, which are enabled by engineering the band gap of the perovskite light-harvesting semiconductors with chemical management and integrating with photonic nanostructures, including microcavity, are discussed. We conclude by providing future research directions toward further performance improvements of the semitransparent perovskite solar cells. Full article

(This article belongs to the Special Issue Perovskite Solar Cells)

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55 pages, 16808 KiB

Open AccessReview

Microwave-Assisted Synthesis of Bioactive Six-Membered Heterocycles and Their Fused Analogues

by Mohsine Driowya, Aziza Saber, Hamid Marzag, Luc Demange, Rachid Benhida and Khalid Bougrin

Molecules 2016, 21(4), 492; https://doi.org/10.3390/molecules21040492 - 14 Apr 2016

Cited by 40 | Viewed by 17785

Abstract

This review describes the formation of six-membered heterocyclic compounds and their fused analogues under microwave activation using modern organic transformations including cyclocondensation, cycloaddition, multicomponents and other modular reactions. The review is divided according to the main heterocycle types in order of increasing complexity, [...] Read more.

This review describes the formation of six-membered heterocyclic compounds and their fused analogues under microwave activation using modern organic transformations including cyclocondensation, cycloaddition, multicomponents and other modular reactions. The review is divided according to the main heterocycle types in order of increasing complexity, starting with heterocyclic systems containing one, two and three heteroatoms and their fused analogues. Recent microwave applications are reviewed, with special focus on the chemistry of bioactive compounds. Selected examples from the 2006 to 2015 literature are discussed. Full article

(This article belongs to the Collection Heterocyclic Compounds)

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13 pages, 2739 KiB

Open AccessReview

Fruitful Decades for Canthin-6-ones from 1952 to 2015: Biosynthesis, Chemistry, and Biological Activities

by Jiangkun Dai, Na Li, Junru Wang and Uwe Schneider

Molecules 2016, 21(4), 493; https://doi.org/10.3390/molecules21040493 - 15 Apr 2016

Cited by 35 | Viewed by 7544

Abstract

In this review, more than 60 natural canthin-6-one alkaloids and their structures are considered. The biosynthesis, efficient and classic synthetic approaches, and biological activities of canthin-6-one alkaloids, from 1952 to 2015, are discussed. From an analysis of their structural properties and an investigation [...] Read more.

In this review, more than 60 natural canthin-6-one alkaloids and their structures are considered. The biosynthesis, efficient and classic synthetic approaches, and biological activities of canthin-6-one alkaloids, from 1952 to 2015, are discussed. From an analysis of their structural properties and an investigation of the literature, possible future trends for canthin-6-one alkaloids are proposed. The information reported will be helpful in future research on canthin-6-one alkaloids. Full article

(This article belongs to the Section Natural Products Chemistry)

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34 pages, 504 KiB

Open AccessReview

Overview of Antagonists Used for Determining the Mechanisms of Action Employed by Potential Vasodilators with Their Suggested Signaling Pathways

by Yean Chun Loh, Chu Shan Tan, Yung Sing Ch’ng, Mariam Ahmad, Mohd Zaini Asmawi and Mun Fei Yam

Molecules 2016, 21(4), 495; https://doi.org/10.3390/molecules21040495 - 15 Apr 2016

Cited by 26 | Viewed by 8402

Abstract

This paper is a review on the types of antagonists and the signaling mechanism pathways that have been used to determine the mechanisms of action employed for vasodilation by test compounds. Thus, we exhaustively reviewed and analyzed reports related to this topic published [...] Read more.

This paper is a review on the types of antagonists and the signaling mechanism pathways that have been used to determine the mechanisms of action employed for vasodilation by test compounds. Thus, we exhaustively reviewed and analyzed reports related to this topic published in PubMed between the years of 2010 till 2015. The aim of this paperis to suggest the most appropriate type of antagonists that correspond to receptors that would be involved during the mechanistic studies, as well as the latest signaling pathways trends that are being studied in order to determine the route(s) that atest compound employs for inducing vasodilation. The methods to perform the mechanism studies were included. Fundamentally, the affinity, specificity and selectivity of the antagonists to their receptors or enzymes were clearly elaborated as well as the solubility and reversibility. All the signaling pathways on the mechanisms of action involved in the vascular tone regulation have been well described in previous review articles. However, the most appropriate antagonists that should be utilized have never been suggested and elaborated before, hence the reason for this review. Full article

(This article belongs to the Section Medicinal Chemistry)

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25 pages, 10912 KiB

Open AccessReview

Dendrimers and Dendrons as Versatile Building Blocks for the Fabrication of Functional Hydrogels

by Sadik Kaga, Mehmet Arslan, Rana Sanyal and Amitav Sanyal

Molecules 2016, 21(4), 497; https://doi.org/10.3390/molecules21040497 - 15 Apr 2016

Cited by 34 | Viewed by 12232

Abstract

Hydrogels have emerged as a versatile class of polymeric materials with a wide range of applications in biomedical sciences. The judicious choice of hydrogel precursors allows one to introduce the necessary attributes to these materials that dictate their performance towards intended applications. Traditionally, [...] Read more.

Hydrogels have emerged as a versatile class of polymeric materials with a wide range of applications in biomedical sciences. The judicious choice of hydrogel precursors allows one to introduce the necessary attributes to these materials that dictate their performance towards intended applications. Traditionally, hydrogels were fabricated using either polymerization of monomers or through crosslinking of polymers. In recent years, dendrimers and dendrons have been employed as well-defined building blocks in these materials. The multivalent and multifunctional nature of dendritic constructs offers advantages in either formulation or the physical and chemical properties of the obtained hydrogels. This review highlights various approaches utilized for the fabrication of hydrogels using well-defined dendrimers, dendrons and their polymeric conjugates. Examples from recent literature are chosen to illustrate the wide variety of hydrogels that have been designed using dendrimer- and dendron-based building blocks for applications, such as sensing, drug delivery and tissue engineering. Full article

(This article belongs to the Special Issue Functional Dendrimers)

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38 pages, 1664 KiB

Open AccessReview

Natural Phytochemicals in the Treatment and Prevention of Dementia: An Overview

by Rosaliana Libro, Sabrina Giacoppo, Thangavelu Soundara Rajan, Placido Bramanti and Emanuela Mazzon

Molecules 2016, 21(4), 518; https://doi.org/10.3390/molecules21040518 - 21 Apr 2016

Cited by 89 | Viewed by 19860

Abstract

The word dementia describes a class of heterogeneous diseases which etiopathogenetic mechanisms are not well understood. There are different types of dementia, among which, Alzheimer’s disease (AD), vascular dementia (VaD), dementia with Lewy bodies (DLB) and frontotemporal dementia (FTD) are the more common. [...] Read more.

The word dementia describes a class of heterogeneous diseases which etiopathogenetic mechanisms are not well understood. There are different types of dementia, among which, Alzheimer’s disease (AD), vascular dementia (VaD), dementia with Lewy bodies (DLB) and frontotemporal dementia (FTD) are the more common. Currently approved pharmacological treatments for most forms of dementia seem to act only on symptoms without having profound disease-modifying effects. Thus, alternative strategies capable of preventing the progressive loss of specific neuronal populations are urgently required. In particular, the attention of researchers has been focused on phytochemical compounds that have shown antioxidative, anti-amyloidogenic, anti-inflammatory and anti-apoptotic properties and that could represent important resources in the discovery of drug candidates against dementia. In this review, we summarize the neuroprotective effects of the main phytochemicals belonging to the polyphenol, isothiocyanate, alkaloid and cannabinoid families in the prevention and treatment of the most common kinds of dementia. We believe that natural phytochemicals may represent a promising sources of alternative medicine, at least in association with therapies approved to date for dementia. Full article

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

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24 pages, 4082 KiB

Open AccessReview

Bifunctional Phosphorus Dendrimers and Their Properties

by Anne-Marie Caminade and Jean-Pierre Majoral

Molecules 2016, 21(4), 538; https://doi.org/10.3390/molecules21040538 - 23 Apr 2016

Cited by 34 | Viewed by 8401

Abstract

Dendrimers are hyperbranched and monodisperse macromolecules, generally considered as a special class of polymers, but synthesized step-by-step. Most dendrimers have a uniform structure, with a single type of terminal function. However, it is often desirable to have at least two different functional groups. [...] Read more.

Dendrimers are hyperbranched and monodisperse macromolecules, generally considered as a special class of polymers, but synthesized step-by-step. Most dendrimers have a uniform structure, with a single type of terminal function. However, it is often desirable to have at least two different functional groups. This review will discuss the case of bifunctional phosphorus-containing dendrimers, and the consequences for their properties. Besides the terminal functions, dendritic structures may have also a function at the core, or linked off-center to the core, or at the core of dendrons (dendritic wedges). Association of two dendrons having different terminal functions leads to Janus dendrimers (two faces). The internal structure can also possess functional groups on one layer, or linked to one layer, or on several layers. Finally, there are several ways to have two types of terminal functions, besides the case of Janus dendrimers: either each terminal function bears two functions sequentially, or two different functions are linked to each terminal branching point. Examples of each type of structure will be given in this review, as well as practical uses of such sophisticated structures in the fields of fluorescence, catalysis, nanomaterials and biology. Full article

(This article belongs to the Special Issue Functional Dendrimers)

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14 pages, 242 KiB

Open AccessReview

Selenium in Cattle: A Review

by Youcef Mehdi and Isabelle Dufrasne

Molecules 2016, 21(4), 545; https://doi.org/10.3390/molecules21040545 - 23 Apr 2016

Cited by 231 | Viewed by 16830

Abstract

This review article examines the role of selenium (Se) and the effects of Se supplementation especially in the bovine species. Selenium is an important trace element in cattle. Some of its roles include the participation in the antioxidant defense the cattle farms. The [...] Read more.

This review article examines the role of selenium (Se) and the effects of Se supplementation especially in the bovine species. Selenium is an important trace element in cattle. Some of its roles include the participation in the antioxidant defense the cattle farms. The nutritional requirements of Se in cattle are estimated at 100 μg/kg DM (dry matter) for beef cattle and at 300 μg/kg DM for dairy cows. The rations high in fermentable carbohydrates, nitrates, sulfates, calcium or hydrogen cyanide negatively influence the organism’s use of the selenium contained in the diet. The Se supplementation may reduce the incidence of metritis and ovarian cysts during the postpartum period. The increase in fertility when adding Se is attributed to the reduction of the embryonic death during the first month of gestation. A use of organic Se in feed would provide a better transfer of Se in calves relative to mineral Se supplementation. The addition of Se yeasts in the foodstuffs of cows significantly increases the Se content and the percentage of polyunsaturated fatty acids (PUFA) in milk compared to the addition of sodium selenite. The enzyme 5-iodothyronine deiodinase is a seleno-dependent selenoprotein. It is one of the last proteins to be affected in the event of Se deficiency. This delay in response could explain the fact that several studies did not show the effect of Se supplementation on growth and weight gain of calves. Enrichment of Se in the diet did not significantly affect the slaughter weight and carcass yield of bulls. The impact and results of Se supplementation in cattle depend on physiological stage, Se status of animals, type and content of Se and types of Se administration. Further studies in Se supplementation should investigate the speciation of Se in food and yeasts, as well as understanding their metabolism and absorption. This constitute a path to exploit in order to explain certain different effects of Se. Full article

(This article belongs to the Section Molecular Diversity)