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Molecules, Volume 20, Issue 4 (April 2015), Pages 5260-7437

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Open AccessArticle Synthesis and Biological Properties of 5-(1H-1,2,3-Triazol-4-yl)isoxazolidines: A New Class of C-Nucleosides
Molecules 2015, 20(4), 5260-5275; doi:10.3390/molecules20045260
Received: 4 February 2015 / Revised: 9 March 2015 / Accepted: 13 March 2015 / Published: 24 March 2015
Cited by 10 | PDF Full-text (702 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A novel series of C-nucleosides, featuring the presence of a 1,2,3-triazole ring linked to an isoxazolidine system, has been designed as mimetics of the pyrimidine nucleobases. An antiproliferative effect was observed for compounds 17a and 17b: the growth inhibitory effect reaches
[...] Read more.
A novel series of C-nucleosides, featuring the presence of a 1,2,3-triazole ring linked to an isoxazolidine system, has been designed as mimetics of the pyrimidine nucleobases. An antiproliferative effect was observed for compounds 17a and 17b: the growth inhibitory effect reaches the 50% in HepG2 and HT-29 cells and increases up to 56% in the SH-SY5Y cell line after 72 h of incubation at a 100 µM concentration. Full article
(This article belongs to the Special Issue Nucleoside Modifications) Printed Edition available
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Open AccessCommunication Optimization of Solid-Supported Glaser-Hay Reactions in the Microwave
Molecules 2015, 20(4), 5276-5285; doi:10.3390/molecules20045276
Received: 13 February 2015 / Revised: 9 March 2015 / Accepted: 18 March 2015 / Published: 24 March 2015
Cited by 3 | PDF Full-text (841 KB) | HTML Full-text | XML Full-text
Abstract
The translation of organometallic reactions into a microwave reactor has numerous advantages. Herein, we describe the application of a previously developed solid-supported Glaser-Hay reaction to microwave conditions. Overall, an array of diynes has been prepared demonstrating the ability to conduct chemoselective reactions in
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The translation of organometallic reactions into a microwave reactor has numerous advantages. Herein, we describe the application of a previously developed solid-supported Glaser-Hay reaction to microwave conditions. Overall, an array of diynes has been prepared demonstrating the ability to conduct chemoselective reactions in the microwave within 20 min compared to the 16 h thermal conditions. Moreover, non-microwave transparent alkynes have been found to react more quickly, preventing catalyst quenching, and resulting in higher yields. Full article
(This article belongs to the Special Issue Organic Synthesis on Solid Phase)
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Open AccessArticle In Vivo Efficacy and Toxicity Studies of a Novel Antibacterial Agent: 14-O-[(2-Amino-1,3,4-thiadiazol-5-yl)Thioacetyl] Mutilin
Molecules 2015, 20(4), 5299-5312; doi:10.3390/molecules20045299
Received: 26 January 2015 / Revised: 17 March 2015 / Accepted: 18 March 2015 / Published: 24 March 2015
Cited by 1 | PDF Full-text (2193 KB) | HTML Full-text | XML Full-text
Abstract
A new pleuromutilin derivative with excellent antibacterial activity, 14-O-[(2-amino-1,3,4-thiadiazol-5-yl) thioacetyl] mutilin (ATTM), may serve as a possible lead compound for the development of antibacterial drugs. However, in vivo efficacy and toxicity evaluations of this compound have not been performed. In this
[...] Read more.
A new pleuromutilin derivative with excellent antibacterial activity, 14-O-[(2-amino-1,3,4-thiadiazol-5-yl) thioacetyl] mutilin (ATTM), may serve as a possible lead compound for the development of antibacterial drugs. However, in vivo efficacy and toxicity evaluations of this compound have not been performed. In this study, we evaluated the efficacy of ATTM by measuring the survival of mice after a lethal challenge with methicillin-resistant Staphylococcus aureus (MRSA), and the 50% effective dose (ED50) was 5.74 mg/kg by the intravenous route. In an oral single-dose toxicity study, ATTM was orally administered to mice at different doses and the 50% lethal dose (LD50) was calculated to be 2304.4 mg/kg by the Bliss method. The results of the subchronic oral toxicity study in rats showed no mortality, exterior signs of toxicity, or differences in the total weight gain or relative organ weights between the treated groups and control group after administration. The hematological and serum biochemical data showed no differences between the treated and control groups, except for the levels of alkaline phosphatase (ALP), creatinine (CR) and blood glucose (GLU), which were significantly different in the high-dose group. The differences in the histopathological findings between the treated groups and the control group were not considered to be treatment-related. Our results indicated that the no observed adverse effect level (NOAEL) for ATTM was 5 mg/kg in this study. Full article
Open AccessArticle Zinc Complexes Containing Coumarin-Derived Anilido-Aldimine Ligands as Catalysts for Ring Opening Polymerization of L-Lactide
Molecules 2015, 20(4), 5313-5328; doi:10.3390/molecules20045313
Received: 12 February 2015 / Revised: 13 March 2015 / Accepted: 20 March 2015 / Published: 24 March 2015
Cited by 5 | PDF Full-text (2855 KB) | HTML Full-text | XML Full-text
Abstract
The coumarin-derived ligand precursors L1HL6H have been prepared. Treatment of these ligand precursors with 1.2 equiv. of ZnEt2 in toluene affords zinc ethyl complexes (LZnEt) 16 (where L = coumarin-derived ligands bearing different functional
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The coumarin-derived ligand precursors L1HL6H have been prepared. Treatment of these ligand precursors with 1.2 equiv. of ZnEt2 in toluene affords zinc ethyl complexes (LZnEt) 16 (where L = coumarin-derived ligands bearing different functional groups). Reaction of ligand precursor L3H with 1.5 equiv. of Zn[N(SiMe3)2]2 in toluene affords the zinc amide complex, L3ZnN(SiMe3)2, 7. All these compounds were characterized by NMR spectroscopy and elemental analysis. The molecular structures are reported for 1 and 7. The catalytic activities of complexes 17 towards the ring opening polymerization of l-lactide in the presence of 9-AnOH have been investigated. Full article
(This article belongs to the Special Issue Ring-Opening Polymerization)
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Open AccessArticle Economical Synthesis of 13C-Labeled Opiates, Cocaine Derivatives and Selected Urinary Metabolites by Derivatization of the Natural Products
Molecules 2015, 20(4), 5329-5345; doi:10.3390/molecules20045329
Received: 10 November 2014 / Revised: 10 February 2015 / Accepted: 19 March 2015 / Published: 25 March 2015
PDF Full-text (571 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The illegal use of opiates and cocaine is a challenge world-wide, but some derivatives are also valuable pharmaceuticals. Reference samples of the active ingredients and their metabolites are needed both for controlling administration in the clinic and to detect drugs of abuse. Especially,
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The illegal use of opiates and cocaine is a challenge world-wide, but some derivatives are also valuable pharmaceuticals. Reference samples of the active ingredients and their metabolites are needed both for controlling administration in the clinic and to detect drugs of abuse. Especially, 13C-labeled compounds are useful for identification and quantification purposes by mass spectroscopic techniques, potentially increasing accuracy by minimizing ion alteration/suppression effects. Thus, the synthesis of [acetyl-13C4]heroin, [acetyl-13C4-methyl-13C]heroin, [acetyl-13C2-methyl-13C]6-acetylmorphine, [N-methyl-13C-O-metyl-13C]codeine and phenyl-13C6-labeled derivatives of cocaine, benzoylecgonine, norcocaine and cocaethylene was undertaken to provide such reference materials. The synthetic work has focused on identifying 13C atom-efficient routes towards these derivatives. Therefore, the 13C-labeled opiates and cocaine derivatives were made from the corresponding natural products. Full article
(This article belongs to the collection Bioactive Compounds)
Open AccessArticle Identification of Floral Scent in Chrysanthemum Cultivars and Wild Relatives by Gas Chromatography-Mass Spectrometry
Molecules 2015, 20(4), 5346-5359; doi:10.3390/molecules20045346
Received: 11 January 2015 / Revised: 18 March 2015 / Accepted: 19 March 2015 / Published: 25 March 2015
Cited by 8 | PDF Full-text (1371 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The objective of this study was to identify the major volatile compounds and their relative concentrations in flowers of different chrysanthemum cultivars and their wild relatives. The volatile organic components of fresh flowers were analyzed using a headspace solid-phase microextraction coupled with gas
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The objective of this study was to identify the major volatile compounds and their relative concentrations in flowers of different chrysanthemum cultivars and their wild relatives. The volatile organic components of fresh flowers were analyzed using a headspace solid-phase microextraction coupled with gas chromatography-mass spectrometry. In total, 193 volatile organic components were detected; the major scent components were monoterpenoids and oxygenated monoterpenoids, which accounted for 68.59%–99.93% of the total volatiles in all tested materials except for Chrysanthemum indicum collected from Huangshan, in which they accounted for only 37.45% of total volatiles. The major volatile compounds were camphor, α-pinene, chrysanthenone, safranal, myrcene, eucalyptol, 2,4,5,6,7,7ab-hexahydro-1H-indene, verbenone, β-phellandrene and camphene. In a hierarchical cluster analysis, 39 accessions of Chrysanthemum and its relatives formed six clusters based on their floral volatile compounds. In a principal component analysis, only spider type flowers were located closely on the score plot. The results of this study provide a basis for breeding chrysanthemum cultivars which desirable floral scents. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Synthesis, Antiproliferative Activity and Molecular Properties Predictions of Galloyl Derivatives
Molecules 2015, 20(4), 5360-5373; doi:10.3390/molecules20045360
Received: 11 November 2014 / Revised: 6 March 2015 / Accepted: 9 March 2015 / Published: 25 March 2015
Cited by 3 | PDF Full-text (701 KB) | HTML Full-text | XML Full-text
Abstract
The present study was designed to investigate the in vitro antiproliferative activity against ten human cancer cell lines of a series of galloyl derivatives bearing substituted-1,3,4-oxadiazole and carbohydrazide moieties. The compounds were also assessed in an in silico study of the absorption, distribution,
[...] Read more.
The present study was designed to investigate the in vitro antiproliferative activity against ten human cancer cell lines of a series of galloyl derivatives bearing substituted-1,3,4-oxadiazole and carbohydrazide moieties. The compounds were also assessed in an in silico study of the absorption, distribution, metabolism and excretion (ADME) in the human body using Lipinski’s parameters, the topological polar surface area (TPSA) and percentage of absorption (%ABS). In general, the introduction of N'-(substituted)-arylidene galloyl hydrazides 48 showed a moderate antitumor activity, while the 2-methylthio- and 2-thioxo-1,3,4-oxadiazol-5-yl derivatives 9 and 10 led to increased inhibition of cancer cell proliferation. The precursor compound methyl gallate 2 and the intermediary galloyl hydrazide 3 showed greater antiproliferative activity with GI50 values < 5.54 µM against all human tumor cell lines tested. A higher inhibition effect against ovarian cancer (OVCAR-3) (GI50 = 0.05–5.98 µM) was also shown, with compounds 2, 3, 9 and 10 with GI50 ≤ 0.89 µM standing out in this respect. The in silico study revealed that the compounds showed good intestinal absorption. Full article
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Open AccessArticle Anti-Inflammatory Screening and Molecular Modeling of Some Novel Coumarin Derivatives
Molecules 2015, 20(4), 5374-5391; doi:10.3390/molecules20045374
Received: 2 February 2015 / Revised: 1 March 2015 / Accepted: 3 March 2015 / Published: 26 March 2015
Cited by 11 | PDF Full-text (2188 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Coumarin and their derivatives have drawn much attention in the pharmacological and pharmaceutical fields due to their broad range and diverse biological activities. In the present work, starting from the 6-amino-7-hydroxy-4-methyl-2H-chromen-2-one, a series of 6-(substituted benzylamino)-7-hydroxy-4-methyl-2H-chromen-2-ones 111
[...] Read more.
Coumarin and their derivatives have drawn much attention in the pharmacological and pharmaceutical fields due to their broad range and diverse biological activities. In the present work, starting from the 6-amino-7-hydroxy-4-methyl-2H-chromen-2-one, a series of 6-(substituted benzylamino)-7-hydroxy-4-methyl-2H-chromen-2-ones 111 was synthesized and assessed for their anti-inflammatory activity using the carrageenan-induced hind paw edema method. Compounds 2, 3, 4 and 9 showed significant (p < 0.001) reduction of rat paw edema volume after 1 h from the administration of the carrageenan compared to the reference drug, indomethacin. On the other hand, compounds 4 and 8 showed the highest anti-inflammatory activity, surpassing indomethacin after 3 h with 44.05% and 38.10% inhibition, respectively. Additionally, a molecular docking study was performed against the COX enzyme using the MOE 10.2010 software. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle New 1-(3-Nitrophenyl)-5,6-dihydro-4H-[1,2,4]triazolo[4,3-a][1,5]benzodiazepines: Synthesis and Computational Study
Molecules 2015, 20(4), 5392-5408; doi:10.3390/molecules20045392
Received: 6 January 2015 / Revised: 18 March 2015 / Accepted: 20 March 2015 / Published: 26 March 2015
Cited by 1 | PDF Full-text (1848 KB) | HTML Full-text | XML Full-text
Abstract
Triazole derivatives constitute an important group of heterocyclic compounds have have been the subject of extensive study in the recent past. These compounds have shown a wide range of biological and pharmacological activities. In this work, new fused tricyclic 1-(3-nitrophenyl)-5,6-dihydro-4H-[1,2,4]triazolo[4,3-a
[...] Read more.
Triazole derivatives constitute an important group of heterocyclic compounds have have been the subject of extensive study in the recent past. These compounds have shown a wide range of biological and pharmacological activities. In this work, new fused tricyclic 1-(3-nitrophenyl)-5,6-dihydro-4H-[1,2,4]triazolo[4,3-a][1,5]-benzodiazepines have been synthesized by the thermal cyclization of N'-(2,3-dihydro-1H-1,5-benzodiazepin-4-yl)-3-nitrobenzohydrazides. After screening ethanol, toluene and 1-butanol as solvents, butanol-1 was found to be the best choice for the cyclization reaction in order to obtain the highest yields of tricyclic derivatives. The chemical structures of the synthesized compounds were elucidated by the analysis of their IR, 1H- and 13C-NMR spectral data. For tentative rationalization of the reaction processes, the global and local reactivity indices of certain compounds, taking part in the reaction pathway, were assessed by means of quantum mechanical calculations using the conceptual density functional theory (DFT) approach. This work could be useful for the synthesis of new heterocyclic compounds bearing a fused triazole ring. Full article
(This article belongs to the Section Organic Synthesis)
Open AccessArticle Formylation of Electron-Rich Aromatic Rings Mediated by Dichloromethyl Methyl Ether and TiCl4: Scope and Limitations
Molecules 2015, 20(4), 5409-5422; doi:10.3390/molecules20045409
Received: 27 January 2015 / Revised: 8 March 2015 / Accepted: 12 March 2015 / Published: 26 March 2015
Cited by 5 | PDF Full-text (844 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Here the aromatic formylation mediated by TiCl4 and dichloromethyl methyl ether previously described by our group has been explored for a wide range of aromatic rings, including phenols, methoxy- and methylbenzenes, as an excellent way to produce aromatic aldehydes. Here we determine
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Here the aromatic formylation mediated by TiCl4 and dichloromethyl methyl ether previously described by our group has been explored for a wide range of aromatic rings, including phenols, methoxy- and methylbenzenes, as an excellent way to produce aromatic aldehydes. Here we determine that the regioselectivity of this process is highly promoted by the coordination between the atoms present in the aromatic moiety and those in the metal core. Full article
(This article belongs to the Section Organic Synthesis)
Open AccessArticle Dereplication of Known Nucleobase and Nucleoside Compounds in Natural Product Extracts by Capillary Electrophoresis-High Resolution Mass Spectrometry
Molecules 2015, 20(4), 5423-5437; doi:10.3390/molecules20045423
Received: 17 December 2014 / Revised: 16 March 2015 / Accepted: 19 March 2015 / Published: 26 March 2015
Cited by 6 | PDF Full-text (791 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Nucleobase and nucleoside compounds exist widely in various organisms. An often occurring problem in the discovery of new bioactive compounds from natural products is reisolation of known nucleobase and nucleoside compounds. To resolve this problem, a capillary electrophoresis-high resolution mass spectrometry (CE-HR-MS) method
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Nucleobase and nucleoside compounds exist widely in various organisms. An often occurring problem in the discovery of new bioactive compounds from natural products is reisolation of known nucleobase and nucleoside compounds. To resolve this problem, a capillary electrophoresis-high resolution mass spectrometry (CE-HR-MS) method providing both rapid separation and accurate mass full-scan MS data was developed for the first time to screen and dereplicate known nucleobase and nucleoside compounds in crude extracts of natural products. Instrumental parameters were optimized to obtain optimum conditions for CE separation and electrospray ionization-time-of-flight mass spectrometry (ESI-TOF/MS) detection. The proposed method was verified to be precise, reproducible, and sensitive. Using this method, known nucleobase and nucleoside compounds in different marine medicinal organisms including Syngnathus acus Linnaeus; Hippocampus japonicus Kaup and Anthopleura lanthogrammica Berkly were successfully observed and identified. This work demonstrates that CE-HR-MS combined with an accurate mass database may be used as a powerful tool for dereplicating known nucleobase and nucleoside compounds in different types of natural products. Rapid dereplication of known nucleobase and nucleoside compounds allows researchers to focus on other leads with greater potential to yield new substances. Full article
(This article belongs to the Special Issue New Technologies for the Recovery of Natural Products)
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Open AccessArticle Synthesis of Photochromic Oligophenylenimines: Optical and Computational Studies
Molecules 2015, 20(4), 5440-5455; doi:10.3390/molecules20045440
Received: 1 January 2015 / Revised: 16 March 2015 / Accepted: 17 March 2015 / Published: 27 March 2015
Cited by 1 | PDF Full-text (2102 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Phenyleneimine oligomers 4,4'-(((1E,1'E)-(((1E,1'E)-(1,4-phenylenebis-(azanylylidene))bis(methanylylidene))bis(2,5-bis(octyloxy)-4,1-phenylene))bis(methanylyl-idene))-bis(azanylylidene))dianiline (OIC1MS) and 7,7'-(((1E,1'E)-(((1E,1'E)-((9H-fluorene-2,7-diyl)bis(azanylylidene))bis(methanylylidene))bis(2,5-bis(octyloxy)-4,1phenylene))bis- (methanylylidene))bis(azanylylidene))bis(9H-fluoren-2-amine) (OIC2MS) were prepared by means of conventional and mechanochemical synthesis and characterized
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Phenyleneimine oligomers 4,4'-(((1E,1'E)-(((1E,1'E)-(1,4-phenylenebis-(azanylylidene))bis(methanylylidene))bis(2,5-bis(octyloxy)-4,1-phenylene))bis(methanylyl-idene))-bis(azanylylidene))dianiline (OIC1MS) and 7,7'-(((1E,1'E)-(((1E,1'E)-((9H-fluorene-2,7-diyl)bis(azanylylidene))bis(methanylylidene))bis(2,5-bis(octyloxy)-4,1phenylene))bis- (methanylylidene))bis(azanylylidene))bis(9H-fluoren-2-amine) (OIC2MS) were prepared by means of conventional and mechanochemical synthesis and characterized by FT-IR, 1H- and 13C-NMR techniques. The optical properties of the compounds were studied in solution by using UV-visible spectroscopy, and the optical effects were analyzed as a function of solvent. The results show that OIC2MS exhibits interesting photochromic properties. Furthermore, the structural and electronic properties of the compounds were analyzed by TD-DFT. It was found that the mechanosynthesis is an efficient method for the synthesis of both tetraimines. Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessArticle Cytoprotective Effect of Hispidin against Palmitate-Induced Lipotoxicity in C2C12 Myotubes
Molecules 2015, 20(4), 5456-5467; doi:10.3390/molecules20045456
Received: 9 February 2015 / Revised: 23 March 2015 / Accepted: 24 March 2015 / Published: 27 March 2015
Cited by 3 | PDF Full-text (1235 KB) | HTML Full-text | XML Full-text
Abstract
It is well known that Phellinus linteus, which produces hispidin and its derivatives, possesses antioxidant activities. In this study, we investigated whether hispidin has protective effects on palmitate-induced oxidative stress in C2C12 skeletal muscle cells. Our results showed that palmitate treatment in
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It is well known that Phellinus linteus, which produces hispidin and its derivatives, possesses antioxidant activities. In this study, we investigated whether hispidin has protective effects on palmitate-induced oxidative stress in C2C12 skeletal muscle cells. Our results showed that palmitate treatment in C2C12 myotubes increased ROS generation and cell death as compared with the control. However, pretreatment of hispidin for 8 h improved the survival of C2C12 myotubes against palmitate-induced oxidative stress via inhibition of intracellular ROS production. Hispidin also inhibited palmitate-induced apoptotic nuclear condensation in C2C12 myotubes. In addition, we found that hispidin can suppress cleavage of caspase-3, expression of Bax, and NF-κB translocation. Therefore, these results suggest that hispidin is capable of protecting C2C12 myotubes against palmitate-induced oxidative stress. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Stevia Rebaudiana Bert. Leaf Extracts as a Multifunctional Source of Natural Antioxidants
Molecules 2015, 20(4), 5468-5486; doi:10.3390/molecules20045468
Received: 4 December 2014 / Revised: 13 February 2015 / Accepted: 28 February 2015 / Published: 27 March 2015
Cited by 11 | PDF Full-text (3145 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The aim of the presented study was to characterize the content and biological activity of extracts prepared from dried Stevia rebaudiana leaves with potential application in the food or cosmetic industry. Aqueous (A), ethanolic (E) and glycol-aqueous (GA) extracts were analyzed for the
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The aim of the presented study was to characterize the content and biological activity of extracts prepared from dried Stevia rebaudiana leaves with potential application in the food or cosmetic industry. Aqueous (A), ethanolic (E) and glycol-aqueous (GA) extracts were analyzed for the content of polyphenols and proteins, showing that the highest amount of phenols (15.50 mg/g) and flavonoids (3.85 mg/g) contained GA. All extracts contained significant amount of protein (69.40–374.67 mg/g). Between analyzed stevia extracts (HPLC) GA contained the highest amount of polyphenols, especially ferulic (5.50 mg/g) and rozmaric (4.95 mg/g) acids derivates. The highest antiradical activity against DPPH and ABTS•+ was noted for GA and E (IC50 = 0.38 and 0.71 µg flavonoids/mL). The highest ability to chelate Fe2+ was observed for E (IC50 = 2.08 µg flavonoids/mL). Stevia extracts were also analyzed for their cytotoxicity and fibroblast irritation potential in vitro. E and GA were the most cytotoxic and irritating, probably due to the high content of biologically active phytochemicals. On the other hand, a extract was the most tolerable by the cells. To summarize, the presented study evaluated the potential application of A, E and GA stevia extracts as natural source of antioxidants in the food and cosmetic industry. Full article
(This article belongs to the collection Bioactive Compounds)
Open AccessArticle Nonlinear Optical Properties Tuning in Meso-Tetraphenylporphyrin Derivatives Substituted with Donor/Acceptor Groups in Picosecond and Nanosecond Regimes
Molecules 2015, 20(4), 5554-5565; doi:10.3390/molecules20045554
Received: 27 February 2015 / Revised: 20 March 2015 / Accepted: 23 March 2015 / Published: 27 March 2015
Cited by 3 | PDF Full-text (1052 KB) | HTML Full-text | XML Full-text
Abstract
meso-Tetraphenylporphyrin (TPP) and its two substituted derivatives (meso-tetrakis(4-cyanophenyl)porphyrin [TPP(CN)4] and meso-tetrakis(4-methoxyphenyl)porphyrin [TPP(OMe)4]) were synthesized. Their nonlinear absorption and refraction properties were studied using the Z-scan technique in the picosecond (ps) and nanosecond (ns) regimes. The
[...] Read more.
meso-Tetraphenylporphyrin (TPP) and its two substituted derivatives (meso-tetrakis(4-cyanophenyl)porphyrin [TPP(CN)4] and meso-tetrakis(4-methoxyphenyl)porphyrin [TPP(OMe)4]) were synthesized. Their nonlinear absorption and refraction properties were studied using the Z-scan technique in the picosecond (ps) and nanosecond (ns) regimes. The open aperture Z-scan results reveal that TPP and TPP(CN)4 display an identical reverse saturable absorption (RSA) character in the ps and ns regimes. While TPP(OMe)4 exhibits a transition from saturable absorption (SA) to RSA in the ps regime and a typical RSA character in the ns regime. The closed aperture Z-scan results show that TPP(CN)4 and TPP(OMe)4 have regular enhancement of the magnitude of nonlinear refraction as compared to their parent TPP in both the ps and ns regimes. In addition, the second-order molecular hyperpolarizabilities (γ) of these three porphyrins are calculated, and the γ values of TPP(CN)4 and TPP(OMe)4 are remarkable larger than that of TPP. The introduction of the electron-withdrawing group CN and the electron-donating group OMe into TPP has enhanced its nonlinear refraction and γ value, and tuned its nonlinear absorption (TPP(OMe)4), which could be useful for porphyrin-related applications based on the desired NLO properties. Full article
(This article belongs to the Section Organic Synthesis)
Open AccessArticle The Absolute Configuration of Salicortin, HCH-Salicortin and Tremulacin from Populus trichocarpa × deltoides Beaupré
Molecules 2015, 20(4), 5566-5573; doi:10.3390/molecules20045566
Received: 3 February 2015 / Revised: 20 March 2015 / Accepted: 26 March 2015 / Published: 30 March 2015
Cited by 1 | PDF Full-text (873 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The absolute configuration of salicortin, HCH-salicortin and tremulacin, isolated from leaves of Populus trichocarpa × deltoides Beaupré, was determined by comparing spectroscopic data of these compounds with those of idescarpin, isolated from leaves of Idesia polycarpa. All compounds were characterized by nuclear
[...] Read more.
The absolute configuration of salicortin, HCH-salicortin and tremulacin, isolated from leaves of Populus trichocarpa × deltoides Beaupré, was determined by comparing spectroscopic data of these compounds with those of idescarpin, isolated from leaves of Idesia polycarpa. All compounds were characterized by nuclear magnetic resonance spectroscopy, high-resolution mass spectrometry, and circular dichroism spectroscopy. It was found that the hydroxy cyclohexenonoyl (HCH) moiety in all compounds is (S)-configured. In addition, it was shown that leaves of Idesia polycarpa contain high amounts of (−)-idescarpin (1.1%, based on dry weight). Full article
(This article belongs to the Section Natural Products)
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Open AccessCommunication New Flavonolignan Glycosides from the Aerial Parts of Zizania latifolia
Molecules 2015, 20(4), 5616-5624; doi:10.3390/molecules20045616
Received: 6 March 2015 / Revised: 18 March 2015 / Accepted: 24 March 2015 / Published: 30 March 2015
Cited by 4 | PDF Full-text (707 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Two new flavonolignan glycosides, tricin-4'-O-(threo-β-guaiacylglyceryl) ether 7''-O-β-D-glucopyranose (4) and tricin-4'-O-(erythro-β-guaiacylglyceryl) ether 7''-O-β-D-glucopyranose (5) were isolated from the roots of Zizania latifolia, together with tricin-7-O-β-D-glucopyranose
[...] Read more.
Two new flavonolignan glycosides, tricin-4'-O-(threo-β-guaiacylglyceryl) ether 7''-O-β-D-glucopyranose (4) and tricin-4'-O-(erythro-β-guaiacylglyceryl) ether 7''-O-β-D-glucopyranose (5) were isolated from the roots of Zizania latifolia, together with tricin-7-O-β-D-glucopyranose (1), tricin-4'-O-(threo-β-guaiacylglyceryl) ether 7-O-β-D-glucopyranose (2), and tricin-4'-O-(erythro-β-guaiacylglyceryl) ether 7-O-β-D-glucopyranose (3). Their structures were identified on the basis of spectroscopic techniques, including HR-ESI/MS, 1D-NMR (1H, 13C, DEPT), 2D-NMR (gCOSY, gHSQC, gHMBC), and IR spectroscopy. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Design, Synthesis, and Insecticidal Activity of Some Novel Diacylhydrazine and Acylhydrazone Derivatives
Molecules 2015, 20(4), 5625-5637; doi:10.3390/molecules20045625
Received: 26 February 2015 / Revised: 22 March 2015 / Accepted: 25 March 2015 / Published: 30 March 2015
Cited by 8 | PDF Full-text (732 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In this study a series of diacylhydrazine and acylhydrazone derivatives were designed and synthesized according to the method of active group combination and the principles of aromatic group bioisosterism. The structures of the novel derivatives were determined on the basis on 1H-NMR,
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In this study a series of diacylhydrazine and acylhydrazone derivatives were designed and synthesized according to the method of active group combination and the principles of aromatic group bioisosterism. The structures of the novel derivatives were determined on the basis on 1H-NMR, IR and ESI-MS spectral data. All of the compounds were evaluated for their in vivo insecticidal activity against the third instar larvae of Spodoptera exigua Hiibner, Helicoverpa armigera Hubner, Plutella xyllostella Linnaeus and Pieris rapae Linne, respectively, at a concentration of 10 mg/L. The results showed that all of the derivatives displayed high insecticidal activity. Most of the compounds presented higher insecticidal activity against S. exigua than the reference compounds tebufenozide, metaflumizone and tolfenpyrad, and approximately identical insecticidal activity against H. armigera, P. xyllostella and P. rapae as the references metaflumizone and tolfenpyrad. Full article
(This article belongs to the Section Organic Synthesis)
Open AccessArticle Chemical Compositions and Antioxidant Activities of Polysaccharides from the Sporophores and Cultured Products of Armillaria mellea
Molecules 2015, 20(4), 5680-5697; doi:10.3390/molecules20045680
Received: 19 January 2015 / Revised: 17 March 2015 / Accepted: 25 March 2015 / Published: 31 March 2015
Cited by 7 | PDF Full-text (1486 KB) | HTML Full-text | XML Full-text
Abstract
Armillaria mellea is a traditional Chinese medicinal and edible mushroom. Many cultured products of A. mellea have been used to develop commercial medicines in recent years. The chemical composition and activities of the major bioactive chemical components—polysaccharides—may be different because of differences in
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Armillaria mellea is a traditional Chinese medicinal and edible mushroom. Many cultured products of A. mellea have been used to develop commercial medicines in recent years. The chemical composition and activities of the major bioactive chemical components—polysaccharides—may be different because of differences in the raw materials used. Four polysaccharides (SP, CMP, CFBP and CFMP) were obtained from wild sporophores and cultured products (including mycelia, fermentation broth and fermentation mixture) of A. mellea. Their yields, carbohydrate contents, monosaccharide compositions, FT-IR spectra, NMR spectroscopy and antioxidant activities were investigated. All of the polysaccharides were composed of xylose, glucose and galactose without protein. Glucose was the dominant monosaccharide in SP, CMP and CFMP, whereas galactose was the dominant monosaccharide in CFBP. SP and CMP showed higher scavenging DPPH and ABTS•+ activities and reducing power among four polysaccharides. The carbohydrate content and corresponding glucose percentage were positive influences on the antioxidant activities, whereas the corresponding xylose and galactose percentage were negative influences. A. mellea polysaccharides are potential natural antioxidants. Polysaccharides from cultured products, especially mycelia, are good substitutes for SP and are also potential sources for both dietary supplements and food industries. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Isolation and Characterization of Phenolic Compounds and Anthocyanins from Murta (Ugni molinae Turcz.) Fruits. Assessment of Antioxidant and Antibacterial Activity
Molecules 2015, 20(4), 5698-5713; doi:10.3390/molecules20045698
Received: 15 January 2015 / Revised: 25 March 2015 / Accepted: 26 March 2015 / Published: 31 March 2015
Cited by 14 | PDF Full-text (1562 KB) | HTML Full-text | XML Full-text
Abstract
Berry fruit consumption has become important in the promotion of human health, mainly due to their phenolic compounds, which have been associated with protection against different pathologies, as well as antimicrobial and other biological activities. Consequently, there has been a growing interest in
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Berry fruit consumption has become important in the promotion of human health, mainly due to their phenolic compounds, which have been associated with protection against different pathologies, as well as antimicrobial and other biological activities. Consequently, there has been a growing interest in identifying natural antioxidants and antimicrobials from these plants. This study aimed to characterize the phenolic chemical composition and anthocyanin profile of murta (Ugni molinae Turcz.) fruit, and to evaluate the antioxidant and antimicrobial activity of its extracts (ethanolic and methanolic). LC/MS of the ethanolic extracts showed the presence of three major compounds: caffeic acid 3-glu, quercetin-3-glu and quercetin, while in the methanolic acid extract they were cyanidin-3-glucoside, pelargonidin-3-arabinose and delphinidin-3-glucoside. The antioxidant activity of ethanolic extracts (DPPH· and ORAC assays) was higher than that of methanol acid extracts or purified anthocynins. Furthermore, the methanol acid extract showed an inhibitory activity against the bacteria E. coli and S. typhi similar to that of standard antibiotics. The results suggest that the antioxidant activity of the ethanolic extract is regulated by the high content of phenolic compounds and the fruit’s characteristic color is due to the content of pelargonidin-3-arabinose and delphinidin-3-glucoside. The obtained results demonstrated the appreciable antioxidant and antibacterial activities, providing opportunities to explore murta extracts as biopreservatives. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Strophalloside Induces Apoptosis of SGC-7901 Cells through the Mitochondrion-Dependent Caspase-3 Pathway
Molecules 2015, 20(4), 5714-5728; doi:10.3390/molecules20045714
Received: 11 February 2015 / Revised: 18 March 2015 / Accepted: 25 March 2015 / Published: 31 March 2015
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Abstract
Cardenolides with special chemical structures have been considered as effective anti-cancer drugs in clinic trials. Strophalloside is a cardenolide we recently isolated from Antiaris toxicaria obtained from Hainan, China. The aim of this study was to investigate the possible anticancer effects induced by
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Cardenolides with special chemical structures have been considered as effective anti-cancer drugs in clinic trials. Strophalloside is a cardenolide we recently isolated from Antiaris toxicaria obtained from Hainan, China. The aim of this study was to investigate the possible anticancer effects induced by strophalloside and the underlying molecular mechanism. Gastric carcinoma SGC-7901 cells were treated with strophalloside at various concentrations for different times, and resulting cell viability was determined by the MTT assay, and the motility and invasion of tumor cells were assessed by the Transwell chamber assay. Apoptosis were measured by Annexin V-FITC/PI and Hoechst staining. The changes of mitochondrial transmembrane potential were examined by a JC-1 kit. The expressions of pro-apoptotic protein cytochrome c, caspase-3 and caspase-9 were detected by western blotting analysis. The results showed that strophalloside was capable of reducing cell viability, inhibiting cell growth, and suppressing cell migration and invasion in a time- and dose-dependent manner. Mitochondrial membrane potential declined and the concentration of cytochrome c increased in cytoplasm and caspase-3 and caspase-9 were cleaved into activated states, suggesting that cytochrome c was released from the mitochondrion to cytoplasm and finally activated the caspase-dependent apoptosis pathway. Our results indicate that strophalloside is a potential anticancer drug. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle NMR Study of the O-Specific Polysaccharide and the Core Oligosaccharide from the Lipopolysaccharide Produced by Plesiomonas shigelloides O24:H8 (Strain CNCTC 92/89)
Molecules 2015, 20(4), 5729-5739; doi:10.3390/molecules20045729
Received: 2 February 2015 / Revised: 13 March 2015 / Accepted: 17 March 2015 / Published: 1 April 2015
Cited by 2 | PDF Full-text (604 KB) | HTML Full-text | XML Full-text
Abstract
The structures of the O-specific polysacccharide and core oligosaccharide of the lipopolysaccharide from Plesiomonas shigelloides O24:H8, strain CNCTC 92/89, have been investigated by NMR spectroscopy and ESI mass spectrometry. The O-specific polysaccharide was found to be composed of a tetrasaccharide repeating unit consisting
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The structures of the O-specific polysacccharide and core oligosaccharide of the lipopolysaccharide from Plesiomonas shigelloides O24:H8, strain CNCTC 92/89, have been investigated by NMR spectroscopy and ESI mass spectrometry. The O-specific polysaccharide was found to be composed of a tetrasaccharide repeating unit consisting of [→3)-α-FucpNAc-(1→3)-α-GalpNAcA-(1→3)-α-QuipNAc-(1→] and of α-RhapNAc (1→4) linked to the GalpNAcA residue. An identical structure has been reported for the capsular polysaccharide of the clinical isolate of Vibrio vulnificus strain BO62316 [1]. The core oligosaccharide was composed of a decasaccharide which structure is identical with these in P. shigelloides serotype O54 [2] and serotype O37 [3]. Full article
Open AccessArticle Antileishmanial and Cytotoxic Compounds from Valeriana wallichii and Identification of a Novel Nepetolactone Derivative
Molecules 2015, 20(4), 5740-5753; doi:10.3390/molecules20045740
Received: 24 February 2015 / Revised: 26 March 2015 / Accepted: 27 March 2015 / Published: 1 April 2015
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Abstract
The chloroform extract of Valeriana wallichii (V. wallichii) rhizomes was investigated to elucidate the structures responsible for reported antileishmanial activity. Besides bornyl caffeate (1, already been reported by us previously), bioassay-guided fractionation resulted in two additional cinnamic acid derivatives
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The chloroform extract of Valeriana wallichii (V. wallichii) rhizomes was investigated to elucidate the structures responsible for reported antileishmanial activity. Besides bornyl caffeate (1, already been reported by us previously), bioassay-guided fractionation resulted in two additional cinnamic acid derivatives 23 with moderate leishmanicidal activity. The structure of a novel nepetolactone derivative 4 having a cinnamic acid moiety was elucidated by means of spectral analysis. To the best of our knowledge villoside aglycone (5) was isolated from this plant for the first time. The bioassay-guided fractionation yielded two new (compounds 67) and two known valtrates (compounds 89) with leishmanicidal potential against Leishmania major (L. major) promastigotes. In addition, β-bisabolol (10), α-kessyl alcohol (11), valeranone (12), bornyl isovalerate (13) and linarin-2-O-methylbutyrate (14) were identified. This is the first report on the isolation of 4'-demethylpodophyllotoxin (15), podophyllotoxin (16) and pinoresinol (17) in V. wallichii. In total thirteen known and four new compounds were identified from the extract and their cytotoxic and antileishmanial properties were evaluated. Full article
Open AccessArticle Synthesis and QSAR Study of Novel 6-Chloro-3-(2-Arylmethylene-1-methylhydrazino)-1,4,2-benzodithiazine 1,1-Dioxide Derivatives with Anticancer Activity
Molecules 2015, 20(4), 5754-5770; doi:10.3390/molecules20045754
Received: 24 February 2015 / Revised: 25 March 2015 / Accepted: 26 March 2015 / Published: 1 April 2015
Cited by 4 | PDF Full-text (725 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A series of new 6-chloro-3-(2-arylmethylene-1-methylhydrazino)-1,4,2-benzodithiazine 1,1-dioxide derivatives were effectively synthesized from N-methyl-N-(6-chloro-1,1-dioxo-1,4,2-benzodithiazin-3-yl)hydrazines. The intermediate compounds as well as the products, were evaluated for their cytotoxic effects toward three human cancer cell lines. All compounds shown moderate or weak cytotoxic effects
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A series of new 6-chloro-3-(2-arylmethylene-1-methylhydrazino)-1,4,2-benzodithiazine 1,1-dioxide derivatives were effectively synthesized from N-methyl-N-(6-chloro-1,1-dioxo-1,4,2-benzodithiazin-3-yl)hydrazines. The intermediate compounds as well as the products, were evaluated for their cytotoxic effects toward three human cancer cell lines. All compounds shown moderate or weak cytotoxic effects against the tested cancer cell lines, but selective cytotoxic effects were observed. Compound 16 exhibited the most potent cytotoxic activity against the HeLa cell line, with an IC50 value of 10 µM, while 14 was the most active against the MCF-7 and HCT-116 cell lines, affording IC50 values of 15 µM and 16 µM, respectively. The structure-activity relationship was evaluated based on QSAR methodology. The QSAR MCF-7 model indicated that natural charge on carbon atom C13 and energy of highest occupied molecular orbital (HOMO) are highly involved in cytotoxic activity against MCF-7 cell line. The cytotoxic activity of compounds against HCT-116 cell line is dependent on natural charge on carbon atom C13 and electrostatic charge on nitrogen atom N10. The obtained QSAR models could provide guidelines for further development of novel anticancer agents. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Synthesis, Characterization, Crystal Structure and Antimicrobial Activity of Copper(II) Complexes with the Schiff Base Derived from 2-Hydroxy-4-Methoxybenzaldehyde
Molecules 2015, 20(4), 5771-5792; doi:10.3390/molecules20045771
Received: 2 February 2015 / Revised: 23 March 2015 / Accepted: 24 March 2015 / Published: 2 April 2015
Cited by 9 | PDF Full-text (1947 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A novel Schiff base, ethyl 4-[(E)-(2-hydroxy-4-methoxyphenyl)methylene-amino]benzoate (HL), was prepared and structurally characterized on the basis of elemental analyses, 1H NMR, 13C NMR, UV-Vis and IR spectral data. Six new copper(II) complexes, [Cu(L)(NO3)(H2O)2] (
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A novel Schiff base, ethyl 4-[(E)-(2-hydroxy-4-methoxyphenyl)methylene-amino]benzoate (HL), was prepared and structurally characterized on the basis of elemental analyses, 1H NMR, 13C NMR, UV-Vis and IR spectral data. Six new copper(II) complexes, [Cu(L)(NO3)(H2O)2] (1), [Cu(L)2] (2), [Cu(L)(OAc)] (3), [Cu2 (L)2Cl2(H2O)4] (4), [Cu(L)(ClO4)(H2O)] (5) and [Cu2(L2S)(ClO4)(H2O)]ClO4·H2O (6) have been synthesized. The characterization of the newly formed compounds was done by IR, UV-Vis, EPR, FAB mass spectroscopy, elemental and thermal analysis, magnetic susceptibility measurements and molar electric conductivity. The crystal structures of Schiff base and the complex [Cu2(L2S)(ClO4)(H2O)]ClO4·H2O (6) have been determined by single crystal X-ray diffraction studies. Both copper atoms display a distorted octahedral coordination type [O4NS]. This coordination is ensured by three phenol oxygen, two of which being related to the µ-oxo-bridge, the nitrogen atoms of the azomethine group and the sulfur atoms that come from the polydentate ligand. The in vitro antimicrobial activity against Escherichia coli ATCC 25922, Salmonella enteritidis, Staphylococcus aureus ATCC 25923, Enterococcus and Candida albicans strains was studied and compared with that of free ligand. The complexes 1, 2, 5 showed a better antimicrobial activity than the Schiff base against the tested microorganisms. Full article
(This article belongs to the Section Organic Synthesis)
Open AccessArticle X-ray Structures of Precursors of Styrylpyridine-Derivatives Used to Obtain 4-((E)-2-(Pyridin-2-yl)vinyl)benzamido-TEMPO: Synthesis and Characterization
Molecules 2015, 20(4), 5793-5811; doi:10.3390/molecules20045793
Received: 25 February 2015 / Revised: 25 March 2015 / Accepted: 25 March 2015 / Published: 2 April 2015
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Abstract
The synthesis and characterization of the precursor isomers trans-4-(2-(pyridin-2-yl)vinylbenzaldehyde (I), trans-4-(2-(pyridin-4-yl)vinylbenzaldehyde (II), trans-4-(2-(pyridin-2-yl)vinylbenzoic acid (III) and (E)-4-(2-(pydridin-4-yl)vinylbenzoic acid (IV) are reported. These compounds were prepared in order to obtain trans
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The synthesis and characterization of the precursor isomers trans-4-(2-(pyridin-2-yl)vinylbenzaldehyde (I), trans-4-(2-(pyridin-4-yl)vinylbenzaldehyde (II), trans-4-(2-(pyridin-2-yl)vinylbenzoic acid (III) and (E)-4-(2-(pydridin-4-yl)vinylbenzoic acid (IV) are reported. These compounds were prepared in order to obtain trans-4-((E)-2-(pyridin-2-yl)vinyl)benzamide-TEMPO (V). Compounds I and II were obtained by using a Knoevenagel reaction in the absence of a condensing agent and solvent. Oxidation of the aldehyde group using the Jones reagent afforded the corresponding acid forms III and IV. A condensation reaction with 4-amino-TEMPO using oxalyl chloride/DMF/CH2Cl2 provided the 4-((E)-2-(pyridin-2-yl)vinyl)benzamide-TEMPO. Single crystals of compounds I, II and III were obtained and characterized by X-ray diffraction. Compound I belongs to space group P21/c, a = 12.6674(19) Å, b = 7.2173(11) Å, c = 11.5877(14) Å, b = 97.203(13)° and the asymmetric unit was Z = 4, whereas compound II was in the space group P21, with a = 3.85728(9) Å, b = 10.62375(19) Å, c = 12.8625(2) Å, b = 91.722 (2)° and the asymmetric unit was Z = 2. Compound III crystallized as single colorless needle crystals, belonging to the monoclinic system with space group P21, with Z = 2, with a = 3.89359(7) Å, b = 17.7014(3) Å, c = 8.04530(12) Å, b = 94.4030 (16)°. All compounds were completely characterized by IR, 1H-NMR, EI-MS and UV-Vis. Full article
(This article belongs to the Section Organic Synthesis)
Open AccessArticle Characterization at 25 °C of Sodium Hyaluronate in Aqueous Solutions Obtained by Transport Techniques
Molecules 2015, 20(4), 5812-5824; doi:10.3390/molecules20045812
Received: 9 January 2015 / Revised: 23 March 2015 / Accepted: 26 March 2015 / Published: 2 April 2015
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Abstract
Mutual diffusion coefficients, D, were determined for aqueous solutions of sodium hyaluronate (NaHy) at 25 °C and concentrations ranging from 0.00 to 1.00 g·dm−3 using the Taylor dispersion technique. From these experimental data, it was possible to estimate some parameters, such
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Mutual diffusion coefficients, D, were determined for aqueous solutions of sodium hyaluronate (NaHy) at 25 °C and concentrations ranging from 0.00 to 1.00 g·dm−3 using the Taylor dispersion technique. From these experimental data, it was possible to estimate some parameters, such as the hydrodynamic radius Rh, and the diffusion coefficient at infinitesimal concentration, D0, of hyaluronate ion, permitting us to have a better understanding of the structure of these systems of sodium hyaluronate in aqueous solutions. The additional viscosity measurements were done and Huggins constant, kH, and limiting viscosity number, [η], were computed for interaction NaHy/water and NaHy/NaHy determination. Full article
(This article belongs to the collection Advances in Carbohydrate Chemistry)
Open AccessArticle Three New Pigment Protein Tyrosine Phosphatases Inhibitors from the Insect Parasite Fungus Cordyceps gracilioides: Terreusinone A, Pinophilin C and Cryptosporioptide A
Molecules 2015, 20(4), 5825-5834; doi:10.3390/molecules20045825
Received: 29 January 2015 / Revised: 25 March 2015 / Accepted: 25 March 2015 / Published: 2 April 2015
Cited by 1 | PDF Full-text (725 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Three new pigment compounds—terreusinone A (1), pinophilin C (2) and cryptosporioptide A (3)—were isolated from a solid culture of Cordyceps gracilioides. The structures of these compounds were determined by extensive spectroscopic analysis including HRESIMS, 1D- and
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Three new pigment compounds—terreusinone A (1), pinophilin C (2) and cryptosporioptide A (3)—were isolated from a solid culture of Cordyceps gracilioides. The structures of these compounds were determined by extensive spectroscopic analysis including HRESIMS, 1D- and 2D-NMR. The structure of terreusinone A (1) was further confirmed by single-crystal X-ray crystallographic diffraction analysis. In an in vitro activity assay, 1, 2 and 3 exhibited high inhibitory activity against PTP1B, SHP2, CDC25B, LAR and SHP1. Terreusinone A (1) inhibited PTP1B, SHP2, CDC25B, LAR and SHP1 enzyme with IC50 values 12.5, >50, 4.1, 10.6, 5.6 µg/mL, respectively; pinophilin C (2) with IC50 values 6.8, 8.0, 4.5, 4.7, 3.4 µg/mL, respectively; and cryptosporioptide A (3) with IC50 values 7.3, 5.7, 7.6, >50, 4.9 µg/mL, respectively. Full article
(This article belongs to the Section Organic Synthesis)
Open AccessArticle Anisotropy in Bone Demineralization Revealed by Polarized Far-IR Spectroscopy
Molecules 2015, 20(4), 5835-5850; doi:10.3390/molecules20045835
Received: 25 January 2015 / Revised: 24 March 2015 / Accepted: 25 March 2015 / Published: 2 April 2015
Cited by 1 | PDF Full-text (1908 KB) | HTML Full-text | XML Full-text
Abstract
Bone material is composed of an organic matrix of collagen fibers and apatite nanoparticles. Previously, vibrational spectroscopy techniques such as infrared (IR) and Raman spectroscopy have proved to be particularly useful for characterizing the two constituent organic and inorganic phases of bone. In
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Bone material is composed of an organic matrix of collagen fibers and apatite nanoparticles. Previously, vibrational spectroscopy techniques such as infrared (IR) and Raman spectroscopy have proved to be particularly useful for characterizing the two constituent organic and inorganic phases of bone. In this work, we tested the potential use of high intensity synchrotron-based far-IR radiation (50–500 cm−1) to gain new insights into structure and chemical composition of bovine fibrolamellar bone. The results from our study can be summarized in the following four points: (I) compared to far-IR spectra obtained from synthetic hydroxyapatite powder, those from fibrolamellar bone showed similar peak positions, but very different peak widths; (II) during stepwise demineralization of the bone samples, there was no significant change neither to far-IR peak width nor position, demonstrating that mineral dissolution occurred in a uniform manner; (III) application of external loading on fully demineralized bone had no significant effect on the obtained spectra, while dehydration of samples resulted in clear differences. (IV) using linear dichroism, we showed that the anisotropic structure of fibrolamellar bone is also reflected in anisotropic far-IR absorbance properties of both the organic and inorganic phases. Far-IR spectroscopy thus provides a novel way to functionally characterize bone structure and chemistry, and with further technological improvements, has the potential to become a useful clinical diagnostic tool to better assess quality of collagen-based tissues. Full article
(This article belongs to the Special Issue Advances of Vibrational Spectroscopic Technologies in Life Sciences)
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Open AccessArticle Synthesis, Crystal Structures and Spectroscopic Properties of Triazine-Based Hydrazone Derivatives; A Comparative Experimental-Theoretical Study
Molecules 2015, 20(4), 5851-5874; doi:10.3390/molecules20045851
Received: 14 February 2015 / Revised: 18 March 2015 / Accepted: 23 March 2015 / Published: 3 April 2015
Cited by 20 | PDF Full-text (2007 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
We report here a comparative theoretical and experimental study of four triazine-based hydrazone derivatives. The hydrazones are synthesized by a three step process from commercially available benzil and thiosemicarbazide. The structures of all compounds were determined by using the UV-Vis., FT-IR, NMR (
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We report here a comparative theoretical and experimental study of four triazine-based hydrazone derivatives. The hydrazones are synthesized by a three step process from commercially available benzil and thiosemicarbazide. The structures of all compounds were determined by using the UV-Vis., FT-IR, NMR (1H and 13C) spectroscopic techniques and finally confirmed unequivocally by single crystal X-ray diffraction analysis. Experimental geometric parameters and spectroscopic properties of the triazine based hydrazones are compared with those obtained from density functional theory (DFT) studies. The model developed here comprises of geometry optimization at B3LYP/6-31G (d, p) level of DFT. Optimized geometric parameters of all four compounds showed excellent correlations with the results obtained from X-ray diffraction studies. The vibrational spectra show nice correlations with the experimental IR spectra. Moreover, the simulated absorption spectra also agree well with experimental results (within 10–20 nm). The molecular electrostatic potential (MEP) mapped over the entire stabilized geometries of the compounds indicated their chemical reactivates. Furthermore, frontier molecular orbital (electronic properties) and first hyperpolarizability (nonlinear optical response) were also computed at the B3LYP/6-31G (d, p) level of theory. Full article
(This article belongs to the collection Heterocyclic Compounds)
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Open AccessArticle Formulations, Hemolytic and Pharmacokinetic Studies on Saikosaponin a and Saikosaponin d Compound Liposomes
Molecules 2015, 20(4), 5889-5907; doi:10.3390/molecules20045889
Received: 13 February 2015 / Revised: 18 March 2015 / Accepted: 30 March 2015 / Published: 3 April 2015
Cited by 3 | PDF Full-text (1630 KB) | HTML Full-text | XML Full-text
Abstract
The aim of this study was to develop and optimise a saikosaponin a and saikosaponin d compound liposome (SSa-SSd-Lip) formulation with reduced hemolysis and enhanced bioavailability. A screening experiment was done with Plackett–Burman design, and response surface methodology of five factors (EPC/SSa-SSd ratio,
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The aim of this study was to develop and optimise a saikosaponin a and saikosaponin d compound liposome (SSa-SSd-Lip) formulation with reduced hemolysis and enhanced bioavailability. A screening experiment was done with Plackett–Burman design, and response surface methodology of five factors (EPC/SSa-SSd ratio, EPC/Chol ratio, water temperature, pH of PBS, and ultrasound time) was employed to optimise the mean diameter, entrapment efficiency of SSa and SSd, and the reduction of hemolysis for SSa-SSd-Lip. Under the optimal process conditions (EPC/SSa-SSd ratio, EPC/Chol ratio, water temperature and pH of PBS were 26.71, 4, 50 °C and 7.4, respectively), the mean diameter, the entrapment efficiency of SSa, the entrapment efficiency of SSd and the hemolysis were 203 nm, 79.87%, 86.19%, 25.16% (SSa/SSd 12.5 mg/mL), respectively. The pharmacokinetic studies showed that the SSa-SSd-Lip had increased circulation time, decreased Cl, and increased AUC, MRT and T1/2β (p < 0.05) for both SSa and SSd after intravenous administration in comparison with solution. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Enhanced Materials from Nature: Nanocellulose from Citrus Waste
Molecules 2015, 20(4), 5908-5923; doi:10.3390/molecules20045908
Received: 13 November 2014 / Revised: 4 March 2015 / Accepted: 27 March 2015 / Published: 3 April 2015
Cited by 15 | PDF Full-text (3186 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Nanocellulose is a relatively inexpensive, highly versatile bio-based renewable material with advantageous properties, including biodegradability and nontoxicity. Numerous potential applications of nanocellulose, such as its use for the preparation of high-performance composites, have attracted much attention from industry. Owing to the low energy
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Nanocellulose is a relatively inexpensive, highly versatile bio-based renewable material with advantageous properties, including biodegradability and nontoxicity. Numerous potential applications of nanocellulose, such as its use for the preparation of high-performance composites, have attracted much attention from industry. Owing to the low energy consumption and the addition of significant value, nanocellulose extraction from agricultural waste is one of the best alternatives for waste treatment. Different techniques for the isolation and purification of nanocellulose have been reported, and combining these techniques influences the morphology of the resultant fibers. Herein, some of the extraction routes for obtaining nanocellulose from citrus waste are addressed. The morphology of nanocellulose was determined by Scanning Electron Microscopy (SEM) and Field Emission Scanning Electron Microscopy (FESEM), while cellulose crystallinity indexes (CI) from lyophilized samples were determined using solid-state Nuclear Magnetic Resonance (NMR) and X-Ray Diffraction (XRD) measurements. The resultant nanofibers had 55% crystallinity, an average diameter of 10 nm and a length of 458 nm. Full article
(This article belongs to the Special Issue New Trends in Cellulose and Chitin Chemistry)
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Open AccessArticle Carboxylated Acyclonucleosides: Synthesis and RNase A Inhibition
Molecules 2015, 20(4), 5924-5941; doi:10.3390/molecules20045924
Received: 17 December 2014 / Revised: 20 March 2015 / Accepted: 20 March 2015 / Published: 3 April 2015
PDF Full-text (1106 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Strategically designed carboxylated acyclonucleosides have been probed as a new class of RNase A inhibitors. Several experimental and theoretical studies have been performed to compile relevant qualitative and quantitative information regarding the nature and extent of inhibition. The inhibition constant (Ki
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Strategically designed carboxylated acyclonucleosides have been probed as a new class of RNase A inhibitors. Several experimental and theoretical studies have been performed to compile relevant qualitative and quantitative information regarding the nature and extent of inhibition. The inhibition constant (Ki) values were determined using a UV-based kinetics experiment. The changes in the secondary structure of the enzyme upon binding with the inhibitors were obtained from circular dichroism studies. The binding constants for enzyme-inhibitor interactions were determined with the help of fluorescence spectroscopy. Docking studies were performed to reveal the possible binding sites of the inhibitors within the enzyme. The cytosine analogues were found to possess better inhibitory properties in comparison to the corresponding uracil derivatives. An increment in the number of carboxylic acid groups (-COOH) in the inhibitor backbone was found to result in better inhibition. Full article
(This article belongs to the Special Issue Nucleoside Modifications) Printed Edition available
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Open AccessArticle Probing the Relationship between Anti-Pneumocystis carinii Activity and DNA Binding of Bisamidines by Molecular Dynamics Simulations
Molecules 2015, 20(4), 5942-5964; doi:10.3390/molecules20045942
Received: 3 March 2015 / Revised: 26 March 2015 / Accepted: 30 March 2015 / Published: 3 April 2015
Cited by 1 | PDF Full-text (3394 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The anti-Pneumocystis carinii activity of 13 synthetic pentamidine analogs was analyzed. The experimental differences in melting points of DNA dodecamer 5'-(CGCGAATTCGCG)2-3' complexes (ΔTm), and in the biological activity measured using ATP bioluminescence assay (IC50) together with
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The anti-Pneumocystis carinii activity of 13 synthetic pentamidine analogs was analyzed. The experimental differences in melting points of DNA dodecamer 5'-(CGCGAATTCGCG)2-3' complexes (ΔTm), and in the biological activity measured using ATP bioluminescence assay (IC50) together with the theoretical free energy of DNA-ligand binding estimated by the proposed computational protocol, showed that the experimental activity of the tested pentamidines appeared to be due to the binding to the DNA minor groove with extended AT sequences. The effect of heteroatoms in the aliphatic linker, and the sulfonamide or methoxy substituents on the compound inducing changes in the interactions with the DNA minor groove was examined and was correlated with biological activity. In computational analysis, the explicit solvent approximation with the discrete water molecules was taken into account, and the role of water molecules in the DNA-ligand complexes was defined. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle A New 9,10-Dihydrophenanthrene and Cell Proliferative 3,4-δ-Dehydrotocopherols from Stemona tuberosa
Molecules 2015, 20(4), 5965-5974; doi:10.3390/molecules20045965
Received: 9 February 2015 / Revised: 25 March 2015 / Accepted: 30 March 2015 / Published: 3 April 2015
Cited by 5 | PDF Full-text (801 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A new compound, 9,10-dihydro-5-methoxy-8-methyl-2,7-phenanthrenediol (1), was isolated from the roots of Stemona tuberosa Lour. (Stemonaceae) together with two new optically active compounds, (2S,4'R,8'R)-3,4-δ-dehydrotocopherol (2) and (2R,4'R,8'R)-3,4-δ-dehydrotocopherol (
[...] Read more.
A new compound, 9,10-dihydro-5-methoxy-8-methyl-2,7-phenanthrenediol (1), was isolated from the roots of Stemona tuberosa Lour. (Stemonaceae) together with two new optically active compounds, (2S,4'R,8'R)-3,4-δ-dehydrotocopherol (2) and (2R,4'R,8'R)-3,4-δ-dehydrotocopherol (3). The structures of compounds 13 were determined on the basis of spectroscopic data analysis. Compounds 2 and 3 were each purified from a stereoisomeric mixture of 2 and 3 by preparative HPLC using a chiral column for the first time. The absolute configurations at C-2 of 2 and 3 were determined by Circular Dichroism (CD) experiments. As a part of the research to find natural wound healing agents, all isolates and the mixture of 2 and 3 were evaluated for their cell proliferative effects using a mouse fibroblast NIH3T3 and a HeLa human cervical cancer cell line. As a result, 1, 2, 3, or the mixture of 2 and 3 showed 41.6%, 78.4%, 118.6%, 38.2% increases of cell proliferation in the mouse fibroblast NIH3T3 respectively, compared to 28.4% increase of δ-tocopherol. Moreover, none of them induced cancer cell proliferation. Therefore, 3,4-δ-dehydrotocopherols, especially pure isomers 2 and 3 can be suggested as potential wound healing agents. Full article
(This article belongs to the Section Natural Products)
Open AccessCommunication Site-Specific Bioconjugation of an Organometallic Electron Mediator to an Enzyme with Retained Photocatalytic Cofactor Regenerating Capacity and Enzymatic Activity
Molecules 2015, 20(4), 5975-5986; doi:10.3390/molecules20045975
Received: 8 February 2015 / Revised: 20 March 2015 / Accepted: 25 March 2015 / Published: 7 April 2015
Cited by 4 | PDF Full-text (1686 KB) | HTML Full-text | XML Full-text
Abstract
Photosynthesis consists of a series of reactions catalyzed by redox enzymes to synthesize carbohydrates using solar energy. In order to take the advantage of solar energy, many researchers have investigated artificial photosynthesis systems mimicking the natural photosynthetic enzymatic redox reactions. These redox reactions
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Photosynthesis consists of a series of reactions catalyzed by redox enzymes to synthesize carbohydrates using solar energy. In order to take the advantage of solar energy, many researchers have investigated artificial photosynthesis systems mimicking the natural photosynthetic enzymatic redox reactions. These redox reactions usually require cofactors, which due to their high cost become a key issue when constructing an artificial photosynthesis system. Combining a photosensitizer and an Rh-based electron mediator (RhM) has been shown to photocatalytically regenerate cofactors. However, maintaining the high concentration of cofactors available for efficient enzymatic reactions requires a high concentration of the expensive RhM; making this process cost prohibitive. We hypothesized that conjugation of an electron mediator to a redox enzyme will reduce the amount of electron mediators necessary for efficient enzymatic reactions. This is due to photocatalytically regenerated NAD(P)H being readily available to a redox enzyme, when the local NAD(P)H concentration near the enzyme becomes higher. However, conventional random conjugation of RhM to a redox enzyme will likely lead to a substantial loss of cofactor regenerating capacity and enzymatic activity. In order to avoid this issue, we investigated whether bioconjugation of RhM to a permissive site of a redox enzyme retains cofactor regenerating capacity and enzymatic activity. As a model system, a RhM was conjugated to a redox enzyme, formate dehydrogenase obtained from Thiobacillus sp. KNK65MA (TsFDH). A RhM-containing azide group was site-specifically conjugated to p-azidophenylalanine introduced to a permissive site of TsFDH via a bioorthogonal strain-promoted azide-alkyne cycloaddition and an appropriate linker. The TsFDH-RhM conjugate exhibited retained cofactor regenerating capacity and enzymatic activity. Full article
(This article belongs to the Special Issue Bioconjugations)
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Open AccessArticle Potential of Start Codon Targeted (SCoT) Markers to Estimate Genetic Diversity and Relationships among Chinese Elymus sibiricus Accessions
Molecules 2015, 20(4), 5987-6001; doi:10.3390/molecules20045987
Received: 26 January 2015 / Revised: 28 March 2015 / Accepted: 1 April 2015 / Published: 7 April 2015
Cited by 9 | PDF Full-text (1448 KB) | HTML Full-text | XML Full-text
Abstract
Elymus sibiricus as an important forage grass and gene pool for improving cereal crops, that is widely distributed in West and North China. Information on its genetic diversity and relationships is limited but necessary for germplasm collection, conservation and future breeding. Start
[...] Read more.
Elymus sibiricus as an important forage grass and gene pool for improving cereal crops, that is widely distributed in West and North China. Information on its genetic diversity and relationships is limited but necessary for germplasm collection, conservation and future breeding. Start Codon Targeted (SCoT) markers were used for studying the genetic diversity and relationships among 53 E. sibiricus accessions from its primary distribution area in China. A total of 173 bands were generated from 16 SCoT primers, 159 bands of which were polymorphic with the percentage of polymorphic bands (PPB) of 91.91%. Based upon population structure analysis five groups were formed. The cluster analysis separated the accessions into two major clusters and three sub-clusters, similar to results of principal coordinate analysis (PCoA). The molecular variance analysis (AMOVA) showed that genetic variation was greater within geographical regions (50.99%) than between them (49.01%). Furthermore, the study also suggested that collecting and evaluating E. sibiricus germplasm for major geographic regions and special environments broadens the available genetic base and illustrates the range of variation. The results of the present study showed that SCoT markers were efficient in assessing the genetic diversity among E. sibiricus accessions. Full article
(This article belongs to the Section Molecular Diversity)
Open AccessArticle Organic-Inorganic Hybrid Nanoparticles for Bacterial Inhibition: Synthesis and Characterization of Doped and Undoped ONPs with Ag/Au NPs
Molecules 2015, 20(4), 6002-6021; doi:10.3390/molecules20046002
Received: 21 January 2015 / Revised: 9 March 2015 / Accepted: 17 March 2015 / Published: 7 April 2015
Cited by 2 | PDF Full-text (12130 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Organic nanoparticles (ONPs) of lipoic acid and its doped derivatives ONPs/Ag and ONPs/Au were prepared and characterized by UV-Visible, EDS, and TEM analysis. The antibacterial properties of the ONPs ONPs/Ag and ONPs/Au were tested against bacterial strains (Staphylococcus aureus, Bacillus cereus
[...] Read more.
Organic nanoparticles (ONPs) of lipoic acid and its doped derivatives ONPs/Ag and ONPs/Au were prepared and characterized by UV-Visible, EDS, and TEM analysis. The antibacterial properties of the ONPs ONPs/Ag and ONPs/Au were tested against bacterial strains (Staphylococcus aureus, Bacillus cereus, Escherichia coli and Salmonella typhi). Minimal Inhibitory Concentration (MIC) and bacterial growth inhibition tests show that ONPs/Ag are more effective in limiting bacterial growth than other NPs, particularly, for Gram positive than for Gram-negative ones. The order of bacterial cell growth inhibition was ONPs/Ag > ONPs > ONPs/Au. The morphology of the cell membrane for the treated bacteria was analyzed by SEM. The nature of bond formation of LA with Ag or Au was analyzed by molecular orbital and density of state (DOS) using DFT. Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessArticle Nanocapsular Dispersion of Cinnamaldehyde for Enhanced Inhibitory Activity against Aflatoxin Production by Aspergillus flavus
Molecules 2015, 20(4), 6022-6032; doi:10.3390/molecules20046022
Received: 10 March 2015 / Revised: 31 March 2015 / Accepted: 1 April 2015 / Published: 7 April 2015
Cited by 5 | PDF Full-text (1781 KB) | HTML Full-text | XML Full-text
Abstract
Cinnamaldehyde (CA) is marginally soluble in water, making it challenging to evenly disperse it in foods, and resulting in lowered anti-A. flavus efficacy. In the present study, nano-dispersed CA (nano-CA) was prepared to increase its aqueous solubility. Free and nano-dispersed CA were
[...] Read more.
Cinnamaldehyde (CA) is marginally soluble in water, making it challenging to evenly disperse it in foods, and resulting in lowered anti-A. flavus efficacy. In the present study, nano-dispersed CA (nano-CA) was prepared to increase its aqueous solubility. Free and nano-dispersed CA were compared in terms of their inhibitory activity against fungal growth and aflatoxin production of A. flavus both in Sabouraud Dextrose (SD) culture and in peanut butter. Our results indicated that free CA inhibited the mycelia growth and aflatoxin production of A. flavus with a minimal inhibitory concentration (MIC) value of 1.0 mM, but promoted the aflatoxin production at some concentrations lower than the MIC. Nano-CA had a lower MIC value of 0.8 mM against A. flavus, and also showed improved activity against aflatoxin production without the promotion at lower dose. The solidity of peanut butter had an adverse impact on the antifungal activity of free CA, whereas nano-dispersed CA showed more than 2-fold improved activity against the growth of A. flavus. Free CA still promoted AFB1 production at the concentration of 0.25 mM, whereas nano-CA showed more efficient inhibition of AFB1 production in the butter. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Ring-Opening Graft Polymerization of Propylene Carbonate onto Xylan in an Ionic Liquid
Molecules 2015, 20(4), 6033-6047; doi:10.3390/molecules20046033
Received: 27 February 2015 / Revised: 25 March 2015 / Accepted: 2 April 2015 / Published: 7 April 2015
Cited by 10 | PDF Full-text (2210 KB) | HTML Full-text | XML Full-text
Abstract
The amidine organocatalyst 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) is an effective nucleophilic catalyst. Biocomposites with tuneable properties were successfully synthesized by ring-opening graft polymerization (ROGP) of propylene carbonate (PC) onto xylan using DBU as a catalyst in the ionic liquid (IL) 1-allyl-3-methylimidazolium chloride ([Amim]Cl). The effects
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The amidine organocatalyst 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) is an effective nucleophilic catalyst. Biocomposites with tuneable properties were successfully synthesized by ring-opening graft polymerization (ROGP) of propylene carbonate (PC) onto xylan using DBU as a catalyst in the ionic liquid (IL) 1-allyl-3-methylimidazolium chloride ([Amim]Cl). The effects of reaction temperature, reaction time and the molar ratio of PC to anhydroxylose units (AXU) in xylan were investigated. The physico-chemical properties of xylan-graft-poly(propylene carbonate) (xylan-g-PPC) copolymers were characterised by FT-IR, NMR, TGA/DTG, AFM and tensile analysis. The FT-IR and NMR results indicated the successful attachment of PPC onto xylan. TGA/DTG suggested the increased thermal stability of xylan after the attachment of PPC side chains. AFM analysis revealed details about the molecular aggregation of xylan-g-PPC films. The results also showed that with the increased DS of xylan-g-PPC copolymers, the tensile strength and Young’s modulus of the films decreased, while the elongation at break increased. Full article
(This article belongs to the Special Issue Ring-Opening Polymerization)
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Open AccessArticle Two Methods for Increased Specificity and Sensitivity in Loop-Mediated Isothermal Amplification
Molecules 2015, 20(4), 6048-6059; doi:10.3390/molecules20046048
Received: 1 February 2015 / Revised: 22 March 2015 / Accepted: 1 April 2015 / Published: 7 April 2015
Cited by 13 | PDF Full-text (962 KB) | HTML Full-text | XML Full-text
Abstract
The technique of loop-mediated isothermal amplification (LAMP) utilizes four (or six) primers targeting six (or eight) regions within a fairly small segment of a genome for amplification, with concentration higher than that used in traditional PCR methods. The high concentrations of primers used
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The technique of loop-mediated isothermal amplification (LAMP) utilizes four (or six) primers targeting six (or eight) regions within a fairly small segment of a genome for amplification, with concentration higher than that used in traditional PCR methods. The high concentrations of primers used leads to an increased likelihood of non-specific amplification induced by primer dimers. In this study, a set of LAMP primers were designed targeting the prfA gene sequence of Listeria monocytogenes, and dimethyl sulfoxide (DMSO) as well as Touchdown LAMP were employed to increase the sensitivity and specificity of the LAMP reactions. The results indicate that the detection limit of this novel LAMP assay with the newly designed primers and additives was 10 fg per reaction, which is ten-fold more sensitive than a commercial Isothermal Amplification Kit and hundred-fold more sensitive than previously reported LAMP assays. This highly sensitive LAMP assay has been shown to detect 11 strains of Listeria monocytogenes, and does not detect other Listeria species (including Listeria innocua and Listeria invanovii), providing some advantages in specificity over commercial Isothermal Amplification Kits and previously reported LAMP assay. Full article
(This article belongs to the Section Molecular Diversity)
Open AccessArticle Development and Characterization of Polymorphic Genic-SSR Markers in Larix kaempferi
Molecules 2015, 20(4), 6060-6067; doi:10.3390/molecules20046060
Received: 14 February 2015 / Revised: 24 March 2015 / Accepted: 26 March 2015 / Published: 8 April 2015
Cited by 5 | PDF Full-text (675 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
New simple sequence repeat (SSR) markers were developed in the Japanese larch (Larix kaempferi) using unigene sequences for further genetic diversity studies and the genetic improvement of breeding programs. One thousand two handred and thirty five (1235) primer pairs were tested
[...] Read more.
New simple sequence repeat (SSR) markers were developed in the Japanese larch (Larix kaempferi) using unigene sequences for further genetic diversity studies and the genetic improvement of breeding programs. One thousand two handred and thirty five (1235) primer pairs were tested and 165 successfully identified in L. kaempferi. Out of the amplified candidate markers, 145 (90.6%) exhibited polymorphism among 24 individuals of L. kaempferi, with the number of alleles per locus (Na), observed heterozygosity (Ho), expected heterozygosity (He) and polymorphic information content (PIC) averaging at 4.510, 0.487, 0.518 and 0.459, respectively. Cross-species amplification of randomly selection of 30 genic-SSRs among the 145 polymorphic ones showed that 80.0% of the SSRs could be amplified in Larix olgensis, 86.7% could be amplified in Larix principi-rupprechtii and 83.0% could be amplified in Larix gmelinii. High rates of cross-species amplification were observed. The genic-SSRs developed herein would be a valuable resource for genetic analysis of Larix kaempferi and related species, and also have the potential to facilitate the genetic improvement and breeding of larch. Full article
(This article belongs to the Section Molecular Diversity)
Open AccessArticle Various Extraction Methods for Obtaining Stilbenes from Grape Cane of Vitis vinifera L.
Molecules 2015, 20(4), 6093-6112; doi:10.3390/molecules20046093
Received: 16 February 2015 / Revised: 30 March 2015 / Accepted: 2 April 2015 / Published: 8 April 2015
Cited by 9 | PDF Full-text (1024 KB) | HTML Full-text | XML Full-text
Abstract
Grape cane, leaves and grape marc are waste products from viticulture, which can be used to obtain secondary stilbene derivatives with high antioxidant value. The presented work compares several extraction methods: maceration at laboratory temperature, extraction at elevated temperature, fluidized-bed extraction, Soxhlet extraction,
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Grape cane, leaves and grape marc are waste products from viticulture, which can be used to obtain secondary stilbene derivatives with high antioxidant value. The presented work compares several extraction methods: maceration at laboratory temperature, extraction at elevated temperature, fluidized-bed extraction, Soxhlet extraction, microwave-assisted extraction, and accelerated solvent extraction. To obtain trans-resveratrol, trans-ε-viniferin and r2-viniferin from grape cane of the V. vinifera variety Cabernet Moravia, various conditions were studied: different solvents, using powdered versus cut cane material, different extraction times, and one-step or multiple extractions. The largest concentrations found were 6030 ± 680 µg/g dry weight (d.w.) for trans-resveratrol, 2260 ± 90 µg/g d.w. for trans-ε-viniferin, and 510 ± 40 µg/g d.w. for r2-viniferin. The highest amounts of stilbenes (8500 ± 1100 µg/g d.w.) were obtained using accelerated solvent extraction in methanol. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Bactericidal Effect of Extracts and Metabolites of Robinia pseudoacacia L. on Streptococcus mutans and Porphyromonas gingivalis Causing Dental Plaque and Periodontal Inflammatory Diseases
Molecules 2015, 20(4), 6128-6139; doi:10.3390/molecules20046128
Received: 6 March 2015 / Revised: 31 March 2015 / Accepted: 2 April 2015 / Published: 8 April 2015
Cited by 5 | PDF Full-text (795 KB) | HTML Full-text | XML Full-text
Abstract
The mouth cavity hosts many types of anaerobic bacteria, including Streptococcus mutans and Porphyromonas gingivalis, which cause periodontal inflammatory diseases and dental caries. The present study was conducted to evaluate the antibacterial potential of extracts of Robinia pseudoacacia and its different fractions,
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The mouth cavity hosts many types of anaerobic bacteria, including Streptococcus mutans and Porphyromonas gingivalis, which cause periodontal inflammatory diseases and dental caries. The present study was conducted to evaluate the antibacterial potential of extracts of Robinia pseudoacacia and its different fractions, as well as some of its natural compounds against oral pathogens and a nonpathogenic reference bacteria, Escherichia coli. The antibacterial activity of the crude extract and the solvent fractions (hexane, chloroform, ethyl acetate and butanol) of R. pseudoacacia were evaluated against S. mutans, P. gingivalis and E. coli DH5α by standard micro-assay procedure using conventional sterile polystyrene microplates. The results showed that the crude extract was more active against P. gingivalis (100% growth inhibition) than against S. mutans (73% growth inhibition) at 1.8 mg/mL. The chloroform and hexane fractions were active against P. gingivalis, with 91 and 97% growth inhibition, respectively, at 0.2 mg/mL. None of seven natural compounds found in R. pseudoacacia exerted an antibacterial effect on P. gingivalis; however, fisetin and myricetin at 8 µg/mL inhibited the growth of S. mutans by 81% and 86%, respectively. The crude extract of R. pseudoacacia possesses bioactive compounds that could completely control the growth of P. gingivalis. The antibiotic activities of the hexane and chloroform fractions suggest that the active compounds are hydrophobic in nature. The results indicate the effectiveness of the plant in clinical applications for the treatment of dental plaque and periodontal inflammatory diseases and its potential use as disinfectant for various surgical and orthodontic appliances. Full article
Open AccessArticle Synthesis of Novel Perfluoroalkylglucosides on Zeolite and Non-Zeolite Catalysts
Molecules 2015, 20(4), 6140-6152; doi:10.3390/molecules20046140
Received: 9 February 2015 / Revised: 27 March 2015 / Accepted: 31 March 2015 / Published: 8 April 2015
PDF Full-text (1635 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Perfluoroalkylglucosides comprise a very important class of fluorine-containing surfactants. These compounds can be synthesized by using the Fisher reaction, starting directly from glucose and the required perfluoroalcohols. We wish to report on the use of zeolite catalysts of different structure and composition for
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Perfluoroalkylglucosides comprise a very important class of fluorine-containing surfactants. These compounds can be synthesized by using the Fisher reaction, starting directly from glucose and the required perfluoroalcohols. We wish to report on the use of zeolite catalysts of different structure and composition for the synthesis of perfluoroalkylglucosides when using glucose and 1-octafluoropentanol as substrates. Zeolites of different pore architecture have been chosen (ZSM-5, ZSM-12, MCM-22 and Beta). Zeolites were characterized by XRD, nitrogen sorption, scanning electron microscopy (SEM) and solid-state 27Al MAS NMR spectroscopy. The activity of the zeolite catalysts in the glycosidation reaction was studied in a batch reactor at 100 °C below atmospheric pressure. The performance of zeolites was compared to other catalysts, an ion-exchange resin (Purolite) and a montmorillonite-type layered aluminosilicate. The catalytic performance of zeolite Beta was the highest among the zeolites studied and the results were comparable to those obtained over Purolite and montmorillonite type catalysts. Full article
(This article belongs to the Special Issue Zeolite Chemistry)
Open AccessArticle Trans-Selective Rhodium Catalysed Conjugate Addition of Organoboron Reagents to Dihydropyranones
Molecules 2015, 20(4), 6153-6166; doi:10.3390/molecules20046153
Received: 10 March 2015 / Revised: 24 March 2015 / Accepted: 1 April 2015 / Published: 8 April 2015
Cited by 2 | PDF Full-text (748 KB) | HTML Full-text | XML Full-text
Abstract
The selective synthesis of 2,6-trans-tetrahydropyran derivatives employing the rhodium catalysed addition of organoboron reagents to dihydropyranone templates, derived from a zinc-catalysed hetero-Diels-Alder reaction, is reported. The addition of both arylboronic acids and potassium alkenyltrifluoroborates have been accomplished in high yields using
[...] Read more.
The selective synthesis of 2,6-trans-tetrahydropyran derivatives employing the rhodium catalysed addition of organoboron reagents to dihydropyranone templates, derived from a zinc-catalysed hetero-Diels-Alder reaction, is reported. The addition of both arylboronic acids and potassium alkenyltrifluoroborates have been accomplished in high yields using commercially-available [Rh(cod)(OH)]2 catalyst. The selective formation of the 2,6-trans-tetrahydropyran stereoisomer is consistent with a mechanism involving alkene association and carbometalation on the less hindered face of the dihydropyranone. Full article
(This article belongs to the Special Issue Recent Advances in Boron Chemistry)
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Open AccessArticle Modular Synthesis of Heparin-Related Tetra-, Hexa- and Octasaccharides with Differential O-6 Protections: Programming for Regiodefined 6-O-Modifications
Molecules 2015, 20(4), 6167-6180; doi:10.3390/molecules20046167
Received: 28 December 2014 / Revised: 6 March 2015 / Accepted: 16 March 2015 / Published: 9 April 2015
Cited by 3 | PDF Full-text (1057 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Heparin and heparan sulphate (H/HS) are important members of the glycosaminoglycan family of sugars that regulate a substantial number of biological processes. Such biological promiscuity is underpinned by hetereogeneity in their molecular structure. The degree of O-sulfation, particularly at the 6-position of
[...] Read more.
Heparin and heparan sulphate (H/HS) are important members of the glycosaminoglycan family of sugars that regulate a substantial number of biological processes. Such biological promiscuity is underpinned by hetereogeneity in their molecular structure. The degree of O-sulfation, particularly at the 6-position of constituent D-GlcN units, is believed to play a role in modulating the effects of such sequences. Synthetic chemistry is essential to be able to extend the diversity of HS-like fragments with defined molecular structure, and particularly to deconvolute the biological significance of modifications at O6. Here we report a synthetic approach to a small matrix of protected heparin-type oligosaccharides, containing orthogonal D-GlcN O-6 protecting groups at programmed positions along the chain, facilitating access towards programmed modifications at specific sites, relevant to sulfation or future mimetics. Full article
(This article belongs to the Special Issue Glycosaminoglycans and Their Mimetics)
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Open AccessArticle Evaluation of the Hypoglycemic Effects of Flavonoids and Extracts from Jatropha gossypifolia L.
Molecules 2015, 20(4), 6181-6193; doi:10.3390/molecules20046181
Received: 23 January 2015 / Revised: 19 March 2015 / Accepted: 23 March 2015 / Published: 9 April 2015
Cited by 3 | PDF Full-text (1875 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Jatropha gossypifolia L. (Euphorbiaceae) is a plant widely used in the treatment of type 2 diabetes mellitus (T2DM), but there are few scientific reports validating its activity in this area. In this work and through a bioguided assay, a crude extract stimulated glucose
[...] Read more.
Jatropha gossypifolia L. (Euphorbiaceae) is a plant widely used in the treatment of type 2 diabetes mellitus (T2DM), but there are few scientific reports validating its activity in this area. In this work and through a bioguided assay, a crude extract stimulated glucose uptake in C2C12 myotubes up to 30%, thereby reducing insulin resistance induced by fatty acids compared to the basal control. A chromatographic fraction applied intraperitoneally (IP) in mice reduced glucose by 42% in a mouse model of T2DM, after administration of 10 doses during 20 days. A flavanone was purified from this active fraction and its structure was assigned by 1H- and 13C-NMR (1D and 2D) and MS. This compound retains the previously reported activity, stimulating in vitro the glucose uptake in a concentration-dependent manner. This study indicates that Jatropha gossypifolia L. extracts enhance glucose uptake in cultured myotubes and adipocytes and also improving glucose tolerance in an in vivo model. Full article
(This article belongs to the collection Bioactive Compounds)
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Open AccessArticle Biological Activities and Cytotoxicity of Diterpenes from Copaifera spp. Oleoresins
Molecules 2015, 20(4), 6194-6210; doi:10.3390/molecules20046194
Received: 14 January 2015 / Revised: 1 April 2015 / Accepted: 2 April 2015 / Published: 9 April 2015
Cited by 4 | PDF Full-text (1142 KB) | HTML Full-text | XML Full-text
Abstract
Copaifera spp. are Amazonian species widely studied and whose oleoresins are used by local people for various medicinal purposes. However, a detailed study of the activity of the main phytochemical components of these oleoresins remains to be done. Here, we studied the cytotoxicity
[...] Read more.
Copaifera spp. are Amazonian species widely studied and whose oleoresins are used by local people for various medicinal purposes. However, a detailed study of the activity of the main phytochemical components of these oleoresins remains to be done. Here, we studied the cytotoxicity and in vitro anti-inflammatory effects of six diterpene acids: copalic, 3-hydroxy-copalic, 3-acetoxy-copalic, hardwickiic, kolavic-15-metyl ester, and kaurenoic, isolated from the oleoresins of Copaifera spp. The diterpenes did not show cytotoxicity in normal cell lines, nor did they show significant changes in viability of tumoral line cells. The 3-hydroxy-copalic was able to inhibit the enzyme tyrosinase (64% ± 1.5%) at 250 µM. The kolavic-15-metyl ester at 200 µM showed high inhibitory effect on lipoxygenase (89.5% ± 1.2%). Among the diterpenes tested, only kaurenoic and copalic acids showed significant hemolytic activities with 61.7% and 38.4% at 100 µM, respectively. In addition, it was observed that only the copalic acid (98.5% ± 1.3%) and hardwickiic acid (92.7% ± 4.9%) at 100 mM inhibited nitric oxide production in macrophages activated by lipopolysaccharide. In this assay, the diterpenes did not inhibit tumor necrosis factor-α production. The acids inhibited the production of IL-6, 3-acetoxy-copalic (23.8% ± 8.2%), kaurenoic (11.2% ± 5.7%), kolavic-15-methyl ester (17.3% ± 4.2%), and copalic (4.2% ± 1.8%), respectively, at 25 µM. The kaurenoic, 3-acetoxy-copalic and copalic acids increased IL-10 production. This study may provide a basis for future studies on the therapeutic role of diterpenic acids in treating acute injuries such as inflammation or skin disorders. Full article
(This article belongs to the collection Bioactive Compounds)
Open AccessArticle Covalent Modification of Human Serum Albumin by the Natural Sesquiterpene Lactone Parthenolide
Molecules 2015, 20(4), 6211-6223; doi:10.3390/molecules20046211
Received: 26 February 2015 / Revised: 30 March 2015 / Accepted: 31 March 2015 / Published: 9 April 2015
Cited by 4 | PDF Full-text (2572 KB) | HTML Full-text | XML Full-text
Abstract
The reactivity of parthenolide (PRT), a natural sesquiterpene lactone from Tanacetum parthenium (Asteraceae), with human serum albumin (HSA) was studied by UHPLC/+ESI-QqTOF MS analysis after tryptic digestion of albumin samples after incubation with this compound. It was found that the single free cysteine
[...] Read more.
The reactivity of parthenolide (PRT), a natural sesquiterpene lactone from Tanacetum parthenium (Asteraceae), with human serum albumin (HSA) was studied by UHPLC/+ESI-QqTOF MS analysis after tryptic digestion of albumin samples after incubation with this compound. It was found that the single free cysteine residue, C34, of HSA (0.6 mM) reacted readily with PRT when incubated at approximately 13-fold excess of PRT (8 mM). Time-course studies with PRT and its 11β,13-dihydro derivative at equimolar ratios of the reactants revealed that PRT under the chosen conditions reacts preferably with C34 and does so exclusively via its α-methylene-γ-lactone moiety, while the epoxide structure is not involved in the reaction. Full article
(This article belongs to the collection Bioactive Compounds)
Open AccessArticle Cu (II)-Catalyzed Asymmetric Henry Reaction with a Novel C1-Symmetric Aminopinane-Derived Ligand
Molecules 2015, 20(4), 6224-6236; doi:10.3390/molecules20046224
Received: 19 February 2015 / Revised: 30 March 2015 / Accepted: 3 April 2015 / Published: 9 April 2015
Cited by 7 | PDF Full-text (757 KB) | HTML Full-text | XML Full-text
Abstract
A novel C1-symmetric dinitrogen ligand was synthesized in high yield from commercially available (1R,2R,3R,5S)-(−)-isopinocampheylamine and 1-methyl-2-imidazolecarboxaldehyde. In combination with Cu(OAc)2H2O, this new ligand promote the reaction between nitromethane and
[...] Read more.
A novel C1-symmetric dinitrogen ligand was synthesized in high yield from commercially available (1R,2R,3R,5S)-(−)-isopinocampheylamine and 1-methyl-2-imidazolecarboxaldehyde. In combination with Cu(OAc)2H2O, this new ligand promote the reaction between nitromethane and aliphatic aldehydes with high yields (up to 97%) and moderate enantioselectivities (up to 67% ee). The reactions with benzaldehyde required prolonged reaction time that resulted in diminished yields, but accompanied with ee-values in the 55%–76% range. Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessArticle Determination of the Primary Molecular Target of 1,2,4-Triazole-Ciprofloxacin Hybrids
Molecules 2015, 20(4), 6254-6272; doi:10.3390/molecules20046254
Received: 1 March 2015 / Revised: 29 March 2015 / Accepted: 1 April 2015 / Published: 9 April 2015
Cited by 8 | PDF Full-text (747 KB) | HTML Full-text | XML Full-text
Abstract
We have synthesized and examined the antibacterial activity, toxicity and affinity towards bacterial type II topoisomerases of a series of 1,2,4-triazole-ciprofloxacin hybrids. A number of these compounds displayed enhanced activity against Gram-positive and Gram-negative bacteria when compared to ciprofloxacin. The toxic concentrations of
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We have synthesized and examined the antibacterial activity, toxicity and affinity towards bacterial type II topoisomerases of a series of 1,2,4-triazole-ciprofloxacin hybrids. A number of these compounds displayed enhanced activity against Gram-positive and Gram-negative bacteria when compared to ciprofloxacin. The toxic concentrations of the obtained derivatives, evaluated on HEK-293 cells using MTT assay, were much higher than concentrations required to produce antibacterial effect. Finally, the results of enzymatic studies showed that the analyzed compounds demonstrated other preferences as regards primary and secondary molecular targets than ciprofloxacin. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Hepatoprotective Triterpene Saponins from the Roots of Glycyrrhiza inflata
Molecules 2015, 20(4), 6273-6283; doi:10.3390/molecules20046273
Received: 4 March 2015 / Revised: 1 April 2015 / Accepted: 2 April 2015 / Published: 9 April 2015
Cited by 8 | PDF Full-text (786 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Two novel oleanane-type triterpene saponins, licorice-saponin P2 (1) and licorice-saponin Q2 (3), together with nine known compounds 2, 411, have been isolated from the water extract of the roots of Glycyrrhiza inflata. The structures
[...] Read more.
Two novel oleanane-type triterpene saponins, licorice-saponin P2 (1) and licorice-saponin Q2 (3), together with nine known compounds 2, 411, have been isolated from the water extract of the roots of Glycyrrhiza inflata. The structures of these compounds were elucidated on the basis of spectroscopic analysis, including 2D-NMR experiments (1H–1H COSY, HSQC, HMBC and ROESY). In in vitro assays, compounds 24, 6 and 11 showed significant hepatoprotective activities by lowering the ALT and AST levels in primary rat hepatocytes injured by D-galactosamine (D-GalN). In addition, compounds 24, 6, 7 and 11 were found to inhibit the activity of PLA2 with IC50 values of 6.9 μM, 3.6 μM, 16.9 μM, 27.1 μM, 32.2 μM and 9.3 μM, respectively, which might be involved in the regulation of the hepatoprotective activities observed. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Synthesis, Photophysical Characterization, and Photoinduced Antibacterial Activity of Methylene Blue-loaded Amino- and Mannose-Targeted Mesoporous Silica Nanoparticles
Molecules 2015, 20(4), 6284-6298; doi:10.3390/molecules20046284
Received: 27 February 2015 / Revised: 29 March 2015 / Accepted: 2 April 2015 / Published: 9 April 2015
Cited by 7 | PDF Full-text (1211 KB) | HTML Full-text | XML Full-text
Abstract
Over the last 20 years, the number of pathogenic multi-resistant microorganisms has grown steadily, which has stimulated the search for new strategies to combat antimicrobial resistance. Antimicrobial photodynamic therapy (aPDT), also called photodynamic inactivation, is emerging as a promising alternative to treatments based
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Over the last 20 years, the number of pathogenic multi-resistant microorganisms has grown steadily, which has stimulated the search for new strategies to combat antimicrobial resistance. Antimicrobial photodynamic therapy (aPDT), also called photodynamic inactivation, is emerging as a promising alternative to treatments based on conventional antibiotics. We have explored the effectiveness of methylene blue-loaded targeted mesoporous silica nanoparticles (MSNP) in the photodynamic inactivation of two Gram negative bacteria, namely Escherichia coli and Pseudomonas aeruginosa. For E. coli, nanoparticle association clearly reduced the dark toxicity of MB while preserving its photoinactivation activity. For P. aeruginosa, a remarkable difference was observed between amino- and mannose-decorated nanoparticles. The details of singlet oxygen production in the nanoparticles have been characterized, revealing the presence of two populations of this cytotoxic species. Strong quenching of singlet oxygen within the nanoparticles is observed. Full article
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Open AccessArticle Silver Nanopartical over AuFON Substrate for Enhanced Raman Readout and Their Application in Pesticide Monitoring
Molecules 2015, 20(4), 6299-6309; doi:10.3390/molecules20046299
Received: 17 December 2014 / Revised: 1 March 2015 / Accepted: 19 March 2015 / Published: 9 April 2015
Cited by 4 | PDF Full-text (2819 KB) | HTML Full-text | XML Full-text
Abstract
Surface-enhanced Raman detection of thiram is demonstrated by using Ag-nanoparticles (Ag NPs) on Au film over nanosphere (AuFON) substrate as the hybrid substrate. The SERS signal of the Ag NPs attached to solid supports is studied. The close coupling together of thousands of
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Surface-enhanced Raman detection of thiram is demonstrated by using Ag-nanoparticles (Ag NPs) on Au film over nanosphere (AuFON) substrate as the hybrid substrate. The SERS signal of the Ag NPs attached to solid supports is studied. The close coupling together of thousands of Ag NPs on AuFON leads to the generation of hot spots for SERS. The Ag NPs on AuFON can be applied to detect rhodamine-6G (R6G) with the detection limitation of 10−11 M and the pesticide thiram in acetone with a detection limit of as low as 0.24 ppm, which is much lower than the maximal residue limit (MRL) of 7 ppm in fruit prescribed by the U.S. Environmental Protection Agency (EPA). The hybrid substrates are shown to be highly sensitive for the detection of thriam, which produce highly enhanced Raman signals with good uniformity and reproducibility due to having plenty of hot spots on its surface. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle A Trinuclear Oxo-Chromium(III) Complex Containing the Natural Flavonoid Primuletin: Synthesis, Characterization, and Antiradical Properties
Molecules 2015, 20(4), 6310-6318; doi:10.3390/molecules20046310
Received: 11 March 2015 / Revised: 30 March 2015 / Accepted: 1 April 2015 / Published: 10 April 2015
Cited by 6 | PDF Full-text (967 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A new trinuclear oxo-centered chromium(III) complex with formula [Cr3O(CH3CO2)6(L)(H2O)2] (L = 5-hydroxyflavone, known as primuletin) was synthetized and characterized by ESI mass spectrometry, thermogravimetry, and 1H-NMR, UV-Vis, and FTIR spectroscopies.
[...] Read more.
A new trinuclear oxo-centered chromium(III) complex with formula [Cr3O(CH3CO2)6(L)(H2O)2] (L = 5-hydroxyflavone, known as primuletin) was synthetized and characterized by ESI mass spectrometry, thermogravimetry, and 1H-NMR, UV-Vis, and FTIR spectroscopies. In agreement with the experimental results, DFT calculations indicated that the flavonoid ligand is coordinated to one of the three Cr(III) centers in an O,O-bidentate mode through the 5-hydroxy/4-keto groups. In a comparative study involving the uncoordinated primuletin and its corresponding complex, systematic reactions with the free radical 2,2-diphenyl-1-picrylhydrazyl (DPPH) showed that antiradical activity increases upon complexation. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Enantioselective Synthesis of cis-Decalins Using Organocatalysis and Sulfonyl Nazarov Reagents
Molecules 2015, 20(4), 6409-6418; doi:10.3390/molecules20046409
Received: 12 March 2015 / Revised: 2 April 2015 / Accepted: 3 April 2015 / Published: 10 April 2015
PDF Full-text (955 KB) | HTML Full-text | XML Full-text
Abstract
The first organocatalytic synthesis of cis-decalins using sulfonyl Nazarov reagents is reported. The Jørgensen’s catalyst directs this highly enantioselective synthesis using different cyclohexenal derivatives. Full article
(This article belongs to the collection Recent Advances in Organocatalysis)
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Open AccessArticle Isolation, Identification and Cytotoxicity of a New Noroleanane-Type Triterpene Saponin from Salicornia bigelovii Torr.
Molecules 2015, 20(4), 6419-6431; doi:10.3390/molecules20046419
Received: 14 February 2015 / Revised: 2 April 2015 / Accepted: 3 April 2015 / Published: 10 April 2015
Cited by 2 | PDF Full-text (1259 KB) | HTML Full-text | XML Full-text
Abstract
Salicornia bigelovii Torr. has been consumed not only as a popular kind of vegetable, but also as a medicinal plant to treat hypertension, cephalalgia, scurvy and cancer. The present study was designed to investigate its chemical components and cytotoxic activity. A new noroleanane-type
[...] Read more.
Salicornia bigelovii Torr. has been consumed not only as a popular kind of vegetable, but also as a medicinal plant to treat hypertension, cephalalgia, scurvy and cancer. The present study was designed to investigate its chemical components and cytotoxic activity. A new noroleanane-type triterpene saponin, bigelovii C (1), was separated and purified from Salicornia bigelovii Torr., along with four known triterpene saponins 25. The structure of bigelovii C was elucidated as 3-O-(6-O-butyl ester)-β-D-glucuropyranosyl-23-aldehyde-30-norolean-12, 20 (29)-dien-28-oic acid-28-O-β-D-glucopyranoside, according to various spectroscopic analysis and chemical characteristics. Besides Compounds 3 and 5, bigelovii C had potent cytotoxicity against three human cancer cell lines, MCF7 (breast cancer), Lovo (colon cancer) and LN229 (glioblastoma), especially MCF7. Bigelovii C inhibited the growth of MCF7 cells in dose- and time-dependent manners. Flow cytometry analysis revealed that the percentage of apoptotic cells significantly increased upon bigelovii C treatment. Rh123 staining assay indicated that bigelovii C reduced the mitochondrial membrane potential. The mechanism of cell death by bigelovii C may be attributed to the downregulation of Bcl-2 and upregulation of Bax, cleaved caspase-9, caspase-7 and PARP. These results suggested that bigelovii C may impart health benefits when consumed and should be regarded as a potential chemopreventative agent for cancer. Full article
(This article belongs to the collection Bioactive Compounds)
Open AccessCommunication Novel Microsatellite Markers Acquired from Rubus coreanus Miq. and Cross-Amplification in Other Rubus Species
Molecules 2015, 20(4), 6432-6442; doi:10.3390/molecules20046432
Received: 13 February 2015 / Revised: 26 March 2015 / Accepted: 7 April 2015 / Published: 10 April 2015
Cited by 3 | PDF Full-text (686 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The Rubus genus consists of more than 600 species that are distributed globally. Only a few Rubus species, including raspberries and blueberries, have been domesticated. Genetic diversity within and between Rubus species is an important resource for breeding programs. We developed genomic
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The Rubus genus consists of more than 600 species that are distributed globally. Only a few Rubus species, including raspberries and blueberries, have been domesticated. Genetic diversity within and between Rubus species is an important resource for breeding programs. We developed genomic microsatellite markers using an SSR-enriched R. coreanus library to study the diversity of the Rubus species. Microsatellite motifs were discovered in 546 of 646 unique clones, and a dinucleotide repeat was the most frequent (75.3%) type of repeat. From 97 microsatellite loci with reproducible amplicons, we acquired 29 polymorphic microsatellite markers in the Rubus coreanus collection. The transferability values ranged from 59.8% to 84% across six Rubus species, and Rubus parvifolius had the highest transferability value (84%). The average number of alleles and the polymorphism information content were 5.7 and 0.541, respectively, in the R. coreanus collection. The diversity index of R. coreanus was similar to the values reported for other Rubus species. A phylogenetic dendrogram based on SSR profiles revealed that seven Rubus species could be allocated to three groups, and that R. coreanus was genetically close to Rubus crataegifolius (mountain berry). These new microsatellite markers might prove useful in studies of the genetic diversity, population structure, and evolutionary relationships among Rubus species. Full article
(This article belongs to the Section Molecular Diversity)
Open AccessArticle Antioxidant and Hepatoprotective Effect of Penthorum chinense Pursh Extract against t-BHP-Induced Liver Damage in L02 Cells
Molecules 2015, 20(4), 6443-6453; doi:10.3390/molecules20046443
Received: 13 February 2015 / Revised: 21 March 2015 / Accepted: 26 March 2015 / Published: 10 April 2015
Cited by 7 | PDF Full-text (4710 KB) | HTML Full-text | XML Full-text
Abstract
Penthorum chinense Pursh (P. chinense), a traditional Chinese medicine used by the Chinese Miao minority, has been used to treat liver diseases for a long time. However, the mechanism behind the liver protective effects of P. chinense remains unclear so far.
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Penthorum chinense Pursh (P. chinense), a traditional Chinese medicine used by the Chinese Miao minority, has been used to treat liver diseases for a long time. However, the mechanism behind the liver protective effects of P. chinense remains unclear so far. The aim of the present study was to investigate the hepatoprotective effect of P. chinense and its possible mechanism(s). Immortalized normal human normal liver L02 cells were used to evaluate the protective effect of P. chinense aqueous extract against tert-butyl hydroperoxide (t-BHP)-induced liver cell damage. Treatment with P. chinense aqueous extract significantly protected L02 cells from t-BHP-induced cytotoxicity, prevented t-BHP-induced reactive oxygen species (ROS) generation and decreased the percentage of apoptosis by inhibiting the mitochondrial apoptotic pathway. This study demonstrates that P. chinense is a potential hepatoprotective agent in t-BHP-induced liver cell damage, which may benefit the further application of P. chinense in the clinic. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle An Ultra-High Performance Liquid Chromatographic-Tandem Mass Spectrometric Method for the Determination of Sinomenine in Human Plasma after Transdermal Delivery of the Zhengqing Fengtongning Injection
Molecules 2015, 20(4), 6454-6465; doi:10.3390/molecules20046454
Received: 10 March 2015 / Revised: 1 April 2015 / Accepted: 2 April 2015 / Published: 10 April 2015
Cited by 1 | PDF Full-text (1173 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A sensitive, precise and selective ultra-high performance liquid chromatography method coupled with triple-quadrupole mass spectrometry was developed and validated for the determination of trace amounts of sinomenine (ng/mL) in minute volumes of human plasma. Fifty microliter plasma samples were precipitated using methanol to
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A sensitive, precise and selective ultra-high performance liquid chromatography method coupled with triple-quadrupole mass spectrometry was developed and validated for the determination of trace amounts of sinomenine (ng/mL) in minute volumes of human plasma. Fifty microliter plasma samples were precipitated using methanol to extract sinomenine. Separation was carried out on a C18 column with a water and acetonitrile mobile phase gradient with formic acid as an additive. The mass spectrometry data were obtained in the positive ion mode, and the transition of multiple reactions was monitored at m/z 330.2→181.0 for sinomenine quantification. The working assay range for sinomenine was linear from 0.1173 to 15.02 ng/mL with the lower limit of quantification of 0.1173 ng/mL. The precision and accuracy of the method was less than 15% in intra-day and inter-day experiments with a matrix effect of less than 6.5%. After validation, the quantitative method was applied to analyze sinomenine levels in human plasma after transdermal delivery of the Zhengqing Fengtongning Injection. The results showed that some samples contained sinomenine within the concentration range 0.4131–4.407 ng/mL. Full article
(This article belongs to the collection Bioactive Compounds)
Open AccessArticle Recycling Antibiotics into GUMBOS: A New Combination Strategy to Combat Multi-Drug-Resistant Bacteria
Molecules 2015, 20(4), 6466-6487; doi:10.3390/molecules20046466
Received: 28 January 2015 / Revised: 28 March 2015 / Accepted: 2 April 2015 / Published: 10 April 2015
Cited by 5 | PDF Full-text (1068 KB) | HTML Full-text | XML Full-text
Abstract
The emergence of multi-drug-resistant bacteria, coupled with the lack of new antibiotics in development, is fast evolving into a global crisis. New strategies utilizing existing antibacterial agents are urgently needed. We propose one such strategy in which four outmoded β-lactam antibiotics (ampicillin, carbenicillin,
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The emergence of multi-drug-resistant bacteria, coupled with the lack of new antibiotics in development, is fast evolving into a global crisis. New strategies utilizing existing antibacterial agents are urgently needed. We propose one such strategy in which four outmoded β-lactam antibiotics (ampicillin, carbenicillin, cephalothin and oxacillin) and a well-known antiseptic (chlorhexidine di-acetate) were fashioned into a group of uniform materials based on organic salts (GUMBOS) as an alternative to conventional combination drug dosing strategies. The antibacterial activity of precursor ions (e.g., chlorhexidine diacetate and β-lactam antibiotics), GUMBOS and their unreacted mixtures were studied with 25 clinical isolates with varying antibiotic resistance using a micro-broth dilution method. Acute cytotoxicity and therapeutic indices were determined using fibroblasts, endothelial and cervical cell lines. Intestinal permeability was predicted using a parallel artificial membrane permeability assay. GUMBOS formed from ineffective β-lactam antibiotics and cytotoxic chlorhexidine diacetate exhibited unique pharmacological properties and profound antibacterial activity at lower concentrations than the unreacted mixture of precursor ions at equivalent stoichiometry. Reduced cytotoxicity to invasive cell types commonly found in superficial and chronic wounds was also observed using GUMBOS. GUMBOS show promise as an alternative combination drug strategy for treating wound infections caused by drug-resistant bacteria. Full article
Open AccessArticle Copolymers of Vinyl-Containing Benzoxazine with Vinyl Monomers as Precursors for High Performance Thermosets
Molecules 2015, 20(4), 6488-6503; doi:10.3390/molecules20046488
Received: 27 February 2015 / Revised: 27 March 2015 / Accepted: 7 April 2015 / Published: 10 April 2015
Cited by 5 | PDF Full-text (1914 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A benzoxazine containing a vinyl group (P-4va) was prepared by the reaction of phenol, 4-vinylaniline, and paraformaldehyde. A differential scanning calorimetry (DSC) study revealed that ring-opening polymerization of the benzoxazine and chain polymerization of the vinyl group occurred in the same temperature range.
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A benzoxazine containing a vinyl group (P-4va) was prepared by the reaction of phenol, 4-vinylaniline, and paraformaldehyde. A differential scanning calorimetry (DSC) study revealed that ring-opening polymerization of the benzoxazine and chain polymerization of the vinyl group occurred in the same temperature range. When 2,2'-azobisisobutyronitrile was added as a radical initiator to P-4va, however, only the vinyl groups were polymerized at lower temperature, giving oligo(P-4va) that contains pendent benzoxazine units. Radical copolymerization of P-4va with various vinyl monomers such as styrene, methyl methacrylate (MMA), and n-butyl acrylate (BuA) was examined. The chemical structure of the copolymers was confirmed by FT-IR and 1H-NMR to be one of polyolefins bearing benzoxazine units as the pendant groups. The weight-average molecular weights of the copolymers determined by size exclusion chromatography were to be in the range of 1900–51,500 depending on the comonomers. DSC of the copolymers showed that the maxima of the exothermic peaks corresponding to the ring-opening polymerization of the pendent benzoxazine units were observed in the temperature range of 229–250 °C. Thermal cure up to 240 °C of the copolymer films afforded homogenous transparent films with improved thermal properties. Tough cured film was obtained by the copolymerization with MMA, while a tough and flexible film was obtained by the copolymerization with BuA. Full article
(This article belongs to the Special Issue Ring-Opening Polymerization)
Open AccessArticle Green Polymer Chemistry: Investigating the Mechanism of Radical Ring-Opening Redox Polymerization (R3P) of 3,6-Dioxa-1,8-octanedithiol (DODT)
Molecules 2015, 20(4), 6504-6519; doi:10.3390/molecules20046504
Received: 28 February 2015 / Revised: 1 April 2015 / Accepted: 7 April 2015 / Published: 13 April 2015
Cited by 2 | PDF Full-text (1556 KB) | HTML Full-text | XML Full-text
Abstract
The mechanism of the new Radical Ring-opening Redox Polymerization (R3P) of 3,6-dioxa-1,8-octanedithiol (DODT) by triethylamine (TEA) and dilute H2O2 was investigated. Scouting studies showed that the formation of high molecular weight polymers required a 1:2 molar ratio of
[...] Read more.
The mechanism of the new Radical Ring-opening Redox Polymerization (R3P) of 3,6-dioxa-1,8-octanedithiol (DODT) by triethylamine (TEA) and dilute H2O2 was investigated. Scouting studies showed that the formation of high molecular weight polymers required a 1:2 molar ratio of DODT to TEA and of DODT to H2O2. Further investigation into the chemical composition of the organic and aqueous phases by 1H-NMR spectroscopy and mass spectrometry demonstrated that DODT is ionized by two TEA molecules (one for each thiol group) and thus transferred into the aqueous phase. The organic phase was found to have cyclic disulfide dimers, trimers and tetramers. Dissolving DODT and TEA in water before the addition of H2O2 yielded a polymer with Mn = 55,000 g/mol, in comparison with Mn = 92,000 g/mol when aqueous H2O2 was added to a DODT/TEA mixture. After polymer removal, MALDI-ToF MS analysis of the residual reaction mixtures showed only cyclic oligomers remaining. Below the LCST for TEA in water, 18.7 °C, the system yielded a stable emulsion, and only cyclic oligomers were found. Below DODT/TEA and H2O2 1:2 molar ratio mostly linear oligomers were formed, with <20% cyclic oligomers. The findings support the proposed mechanism of R3P. Full article
(This article belongs to the Special Issue Ring-Opening Polymerization)
Open AccessArticle A Facile Synthesis and Antimicrobial Activity Evaluation of Sydnonyl-Substituted Thiazolidine Derivatives
Molecules 2015, 20(4), 6520-6532; doi:10.3390/molecules20046520
Received: 10 February 2015 / Revised: 23 March 2015 / Accepted: 2 April 2015 / Published: 13 April 2015
Cited by 3 | PDF Full-text (1069 KB) | HTML Full-text | XML Full-text
Abstract
Some new sydnonyl-substituted thiazolidine derivatives were synthesized in high yields by the modified Knoevenagel condensation of 3-aryl-4-formylsydnones with thiazolidine-2,4-dione and 2-thioxo-thiazolidine-4-one, respectively. All the synthesized thiazolidine derivatives were screened by paper-disc method to identify their antimicrobial activities against three bacteria viz. Staphylococcus aureus
[...] Read more.
Some new sydnonyl-substituted thiazolidine derivatives were synthesized in high yields by the modified Knoevenagel condensation of 3-aryl-4-formylsydnones with thiazolidine-2,4-dione and 2-thioxo-thiazolidine-4-one, respectively. All the synthesized thiazolidine derivatives were screened by paper-disc method to identify their antimicrobial activities against three bacteria viz. Staphylococcus aureus, Proteus vulgaris and Escherichia coli, and two fungal cultures viz. Aspergillus niger and Penicillium citrinum. The reference drugs were Norfloxacin and Griseofulvin, respectively. The screening data indicated that the tested sydnonyl-substituted thiazolidine derivatives exhibited no obvious antibacterial activity compared with the standard drug Norfloxacin. However, thiazolidine derivatives displayed significant antifungal activities against Penicillium citrinum and Aspergillus niger. Notably, all of the tested compounds showed growth inhibitory activity 1.5-4.4 times higher than that of the standard drug Griseofulvin against the two fungi. Full article
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Open AccessArticle Quercitrin, an Inhibitor of Sortase A, Interferes with the Adhesion of Staphylococcal aureus
Molecules 2015, 20(4), 6533-6543; doi:10.3390/molecules20046533
Received: 13 January 2015 / Revised: 5 April 2015 / Accepted: 8 April 2015 / Published: 13 April 2015
Cited by 6 | PDF Full-text (2445 KB) | HTML Full-text | XML Full-text
Abstract
Sortase A (SrtA) is a cysteine transpeptidase of most Gram-positive bacteria that is responsible for the anchorage of many surface protein virulence factors to the cell wall layer. SrtA mutants are unable to display surface proteins and are defective in the establishment of
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Sortase A (SrtA) is a cysteine transpeptidase of most Gram-positive bacteria that is responsible for the anchorage of many surface protein virulence factors to the cell wall layer. SrtA mutants are unable to display surface proteins and are defective in the establishment of infections without affecting microbial viability. In this study, we report that quercitrin (QEN), a natural compound that does not affect Staphylococcus aureus growth, can inhibit the catalytic activity of SrtA in fibrinogen (Fg) cell-clumping and immobilized fibronectin (Fn) adhesion assays. Molecular dynamics simulations and mutagenesis assays suggest that QEN binds to the binding sites of the SrtA G167A and V193A mutants. These findings indicate that QEN is a potential lead compound for the development of new anti-virulence agents against S. aureus infections. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Methanolic Extracts from Brown Seaweeds Dictyota cilliolata and Dictyota menstrualis Induce Apoptosis in Human Cervical Adenocarcinoma HeLa Cells
Molecules 2015, 20(4), 6573-6591; doi:10.3390/molecules20046573
Received: 22 December 2014 / Revised: 23 March 2015 / Accepted: 1 April 2015 / Published: 13 April 2015
Cited by 6 | PDF Full-text (2492 KB) | HTML Full-text | XML Full-text
Abstract
Carcinoma of the uterine cervix is the second most common female tumor worldwide, surpassed only by breast cancer. Natural products from seaweeds evidencing apoptotic activity have attracted a great deal of attention as new leads for alternative and complementary preventive or therapeutic anticancer
[...] Read more.
Carcinoma of the uterine cervix is the second most common female tumor worldwide, surpassed only by breast cancer. Natural products from seaweeds evidencing apoptotic activity have attracted a great deal of attention as new leads for alternative and complementary preventive or therapeutic anticancer agents. Here, methanol extracts from 13 species of tropical seaweeds (Rhodophytas, Phaeophyta and Chlorophyta) collected from the Northeast of Brazil were assessed as apoptosis-inducing agents on human cervical adenocarcinoma (HeLa). All extracts showed different levels of cytotoxicity against HeLa cells; the most potent were obtained from the brown alga Dictyota cilliolata (MEDC) and Dictyota menstrualis (MEDM). In addition, MEDC and MEDM also inhibits SiHa (cervix carcinoma) cell proliferation. Studies with these two extracts using flow cytometry and fluorescence microscopy showed that HeLa cells exposed to MEDM and MEDC exhibit morphological and biochemical changes that characterize apoptosis as shown by loss of cell viability, chromatin condensation, phosphatidylserine externalization, and sub-G1 cell cycle phase accumulation, also MEDC induces cell cycle arrest in cell cycle phase S. Moreover, the activation of caspases 3 and 9 by these extracts suggests a mitochondria-dependent apoptosis route. However, other routes cannot be ruled out. Together, these results point out the methanol extracts of the brown algae D. mentrualis and D. cilliolata as potential sources of molecules with antitumor activity. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Phenylglyoxal-Based Visualization of Citrullinated Proteins on Western Blots
Molecules 2015, 20(4), 6592-6600; doi:10.3390/molecules20046592
Received: 20 March 2015 / Revised: 1 April 2015 / Accepted: 2 April 2015 / Published: 14 April 2015
Cited by 1 | PDF Full-text (631 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Citrullination is the conversion of peptidylarginine to peptidylcitrulline, which is catalyzed by peptidylarginine deiminases. This conversion is involved in different physiological processes and is associated with several diseases, including cancer and rheumatoid arthritis. A common method to detect citrullinated proteins relies on anti-modified
[...] Read more.
Citrullination is the conversion of peptidylarginine to peptidylcitrulline, which is catalyzed by peptidylarginine deiminases. This conversion is involved in different physiological processes and is associated with several diseases, including cancer and rheumatoid arthritis. A common method to detect citrullinated proteins relies on anti-modified citrulline antibodies directed to a specific chemical modification of the citrulline side chain. Here, we describe a versatile, antibody-independent method for the detection of citrullinated proteins on a membrane, based on the selective reaction of phenylglyoxal with the ureido group of citrulline under highly acidic conditions. The method makes use of 4-azidophenylglyoxal, which, after reaction with citrullinated proteins, can be visualized with alkyne-conjugated probes. The sensitivity of this procedure, using an alkyne-biotin probe, appeared to be comparable to the antibody-based detection method and independent of the sequence surrounding the citrulline. Full article
(This article belongs to the Special Issue Advances in Click Chemistry)
Open AccessArticle Four New Pentasaccharide Resin Glycosides from Ipomoea cairica with Strong α-Glucosidase Inhibitory Activity
Molecules 2015, 20(4), 6601-6610; doi:10.3390/molecules20046601
Received: 22 January 2015 / Revised: 2 April 2015 / Accepted: 7 April 2015 / Published: 14 April 2015
Cited by 3 | PDF Full-text (714 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Six pentasaccharide resin glycosides from Ipomoea cairica, including four new acylated pentasaccharide resin glycosides, namely cairicoside I–IV (14) and the two known compounds cairicoside A (5) and cairicoside C (6), were isolated from the
[...] Read more.
Six pentasaccharide resin glycosides from Ipomoea cairica, including four new acylated pentasaccharide resin glycosides, namely cairicoside I–IV (14) and the two known compounds cairicoside A (5) and cairicoside C (6), were isolated from the aerial parts of Ipomoea cairica. Their structures were established by a combination of spectroscopic, including two dimensional (2D) NMR and chemical methods. The core of the six compounds was simonic acid A, and they were esterfied the same sites, just differing in the substituent groups. The lactonization site of the aglycone was bonded to the second saccharide moiety at C-2 in 14, and at C-3 in 56. Compounds 1 and 5, 4 and 6 were two pairs of isomers. The absolute configuration of the aglycone in 16 which was (11S)-hydroxyhexadecanoic acid (jalapinolic acid) was established by Mosher’s method. Compounds 14 have been evaluated for inhibitory activity against α-glucosidase, which all showed inhibitory activities. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Employing Response Surface Methodology for the Optimization of Ultrasound Assisted Extraction of Lutein and β-Carotene from Spinach
Molecules 2015, 20(4), 6611-6625; doi:10.3390/molecules20046611
Received: 6 February 2015 / Revised: 8 April 2015 / Accepted: 10 April 2015 / Published: 14 April 2015
Cited by 7 | PDF Full-text (2400 KB) | HTML Full-text | XML Full-text
Abstract
The extraction of lutein and β-carotene from spinach (Spinacia oleracea L.) leaves is important to the dietary supplement industry. A Box-Behnken design and response surface methodology (RSM) were used to investigate the effect of process variables on the ultrasound-assisted extraction (UAE) of
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The extraction of lutein and β-carotene from spinach (Spinacia oleracea L.) leaves is important to the dietary supplement industry. A Box-Behnken design and response surface methodology (RSM) were used to investigate the effect of process variables on the ultrasound-assisted extraction (UAE) of lutein and β-carotene from spinach. Three independent variables, extraction temperature (°C), extraction power (%) and extraction time (min) were studied. Thin-layer chromatography (TLC) followed by UV visualization and densitometry was used as a simple and rapid method for both identification and quantification of lutein and β-carotene during UAE. Methanol extracts of leaves from spinach and authentic standards of lutein and β-carotene were separated by normal-phase TLC with ethyl acetate-acetone (5:4 (v/v)) as the mobile phase. In this study, the combination of TLC, densitometry, and Box–Behnken with RSM methods were effective for the quantitative analysis of lutein and β-carotene from spinach extracts. The resulting quadratic polynomial models for optimizing lutein and β-carotene from spinach had high coefficients of determination of 0.96 and 0.94, respectively. The optimal UAE settings for output of lutein and β-carotene simultaneously from spinach extracts were an extraction temperature of 40 °C, extraction power of 40% (28 W/cm3) and extraction time of 16 min. The identity and purity of each TLC spot was measured using time-of-flight mass spectrometry. Therefore, UAE assisted extraction of carotenes from spinach can provide a source of lutein and β-carotene for the dietary supplement industry. Full article
(This article belongs to the Special Issue New Technologies for the Recovery of Natural Products)
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Open AccessArticle Epigallocatechin-3-Gallate Protects HUVECs from PM2.5-Induced Oxidative Stress Injury by Activating Critical Antioxidant Pathways
Molecules 2015, 20(4), 6626-6639; doi:10.3390/molecules20046626
Received: 27 February 2015 / Revised: 3 April 2015 / Accepted: 8 April 2015 / Published: 14 April 2015
Cited by 14 | PDF Full-text (1561 KB) | HTML Full-text | XML Full-text
Abstract
Endothelial dysfunction and oxidative stress likely play roles in PM2.5-induced harmful effects. Epigallocatechin-3-gallate (EGCG), the major polyphenolic constituent of green tea, is a potent antioxidant that exerts protective effects on cardiovascular diseases (CVDs) in part by scavenging free radicals. The exposure
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Endothelial dysfunction and oxidative stress likely play roles in PM2.5-induced harmful effects. Epigallocatechin-3-gallate (EGCG), the major polyphenolic constituent of green tea, is a potent antioxidant that exerts protective effects on cardiovascular diseases (CVDs) in part by scavenging free radicals. The exposure to ambient fine particulate matter (PM2.5) is responsible for certain CVDs. The aim of the present study was to investigate whether EGCG could also inhibit PM2.5-induced oxidative stress by activating the nuclear factor E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway in human umbilical vein endothelial cells (HUVECs). PM2.5 (200 μg/mL) increased both cell death and intracellular ROS levels significantly, whereas EGCG (50–400 μM) inhibited these effects in a concentration-dependent manner. Western blotting and PCR demonstrated that EGCG increased Nrf2 and HO-1 expression in HUVECs that had been exposed to PM2.5. PD98059 (a selective inhibitor of extracellular signal regulated kinase [ERK]-1/2) and SB203580 (a selective inhibitor of p38 MAPK), but not SP600125 (a selective inhibitor of c-jun N-terminal kinase [JNK]), attenuated the EGCG-induced Nrf2 and HO-1 expression. In addition, silencing Nrf2 abolished EGCG-induced Nrf2 and HO-1 upregulation and enhancement of cell viability. The present study suggests that EGCG protects HUVECs from PM2.5-induced oxidative stress injury by upregulating Nrf2/HO-1 via activation of the p38 MAPK and the ERK1/2 signaling pathways. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle A Three-Enzyme-System to Degrade Curcumin to Natural Vanillin
Molecules 2015, 20(4), 6640-6653; doi:10.3390/molecules20046640
Received: 18 February 2015 / Revised: 23 March 2015 / Accepted: 7 April 2015 / Published: 14 April 2015
Cited by 2 | PDF Full-text (644 KB) | HTML Full-text | XML Full-text
Abstract
The symmetrical structure of curcumin includes two 4-hydroxy-3-methoxyphenyl substructures. Laccase catalyzed formation of a phenol radical, radical migration and oxygen insertion at the benzylic positions can result in the formation of vanillin. As vanillin itself is a preferred phenolic substrate of laccases, the
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The symmetrical structure of curcumin includes two 4-hydroxy-3-methoxyphenyl substructures. Laccase catalyzed formation of a phenol radical, radical migration and oxygen insertion at the benzylic positions can result in the formation of vanillin. As vanillin itself is a preferred phenolic substrate of laccases, the formation of vanillin oligomers and polymers is inevitable, once vanillin becomes liberated. To decelerate the oligomerization, one of the phenolic hydroxyl groups was protected via acetylation. Monoacetyl curcumin with an approximate molar yield of 49% was the major acetylation product, when a lipase from Candida antarctica (CAL) was used. In the second step, monoacetyl curcumin was incubated with purified laccases of various basidiomycete fungi in a biphasic system (diethyl ether/aqueous buffer). A laccase from Funalia trogii (LccFtr) resulted in a high conversion (46% molar yield of curcumin monoacetate) to vanillin acetate. The non-protected vanillin moiety reacted to a mixture of higher molecular products. In the third step, the protecting group was removed from vanillin acetate using a feruloyl esterase from Pleurotus eryngii (PeFaeA) (68% molar yield). Alignment of the amino acid sequences indicated that high potential laccases performed better in this mediator and cofactor-free reaction. Full article
(This article belongs to the collection Recent Advances in Flavors and Fragrances)
Open AccessArticle Optimization of γ-Aminobutyric Acid Production by Lactobacillus plantarum Taj-Apis362 from Honeybees
Molecules 2015, 20(4), 6654-6669; doi:10.3390/molecules20046654
Received: 13 November 2014 / Revised: 3 December 2014 / Accepted: 29 December 2014 / Published: 15 April 2015
Cited by 8 | PDF Full-text (914 KB) | HTML Full-text | XML Full-text
Abstract
Dominant strains of lactic acid bacteria (LAB) isolated from honey bees were evaluated for their γ-aminobutyric acid (GABA)-producing ability. Out of 24 strains, strain Taj-Apis362 showed the highest GABA-producing ability (1.76 mM) in MRS broth containing 50 mM initial glutamic acid cultured for
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Dominant strains of lactic acid bacteria (LAB) isolated from honey bees were evaluated for their γ-aminobutyric acid (GABA)-producing ability. Out of 24 strains, strain Taj-Apis362 showed the highest GABA-producing ability (1.76 mM) in MRS broth containing 50 mM initial glutamic acid cultured for 60 h. Effects of fermentation parameters, including initial glutamic acid level, culture temperature, initial pH and incubation time on GABA production were investigated via a single parameter optimization strategy. The optimal fermentation condition for GABA production was modeled using response surface methodology (RSM). The results showed that the culture temperature was the most significant factor for GABA production. The optimum conditions for maximum GABA production by Lactobacillus plantarum Taj-Apis362 were an initial glutamic acid concentration of 497.97 mM, culture temperature of 36 °C, initial pH of 5.31 and incubation time of 60 h, which produced 7.15 mM of GABA. The value is comparable with the predicted value of 7.21 mM. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Mouse Mincle: Characterization as a Model for Human Mincle and Evolutionary Implications
Molecules 2015, 20(4), 6670-6682; doi:10.3390/molecules20046670
Received: 13 March 2015 / Revised: 7 April 2015 / Accepted: 13 April 2015 / Published: 15 April 2015
Cited by 8 | PDF Full-text (2652 KB) | HTML Full-text | XML Full-text
Abstract
Mincle, the macrophage-inducible C-type lectin also known as CLEC-4E, binds to the mycobacterial glycolipid trehalose dimycolate and initiates a signaling cascade by serving as a receptor for Mycobacterium tuberculosis and other pathogenic mycobacterial species. Studies of the biological functions of human mincle often
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Mincle, the macrophage-inducible C-type lectin also known as CLEC-4E, binds to the mycobacterial glycolipid trehalose dimycolate and initiates a signaling cascade by serving as a receptor for Mycobacterium tuberculosis and other pathogenic mycobacterial species. Studies of the biological functions of human mincle often rely on mouse models, based on the assumption that the biological properties of the mouse receptor mimic those of the human protein. Experimental support for this assumption has been obtained by expression of the carbohydrate-recognition domain of mouse mincle and characterization of its interaction with small molecule analogs of trehalose dimycolate. The results confirm that the ligand-binding properties of mouse mincle closely parallel those of the human receptor. These findings are consistent with the conservation of key amino acid residues that have been shown to form the ligand-binding site in human and cow mincle. Sequence alignment reveals that these residues are conserved in a wide range of mammalian species, suggesting that mincle has a conserved function in binding ligands that may include endogenous mammalian glycans or pathogen glycans in addition to trehalose dimycolate. Full article
(This article belongs to the Special Issue Protein-Carbohydrate Interactions, and Beyond)
Open AccessArticle Coordination and Crystallization Molecules: Their Interactions Affecting the Dimensionality of Metalloporphyrinic SCFs
Molecules 2015, 20(4), 6683-6699; doi:10.3390/molecules20046683
Received: 5 February 2015 / Revised: 9 March 2015 / Accepted: 8 April 2015 / Published: 15 April 2015
Cited by 3 | PDF Full-text (3188 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Synthetic metalloporphyrin complexes are often used as analogues of natural systems, and they can be used for the preparation of new Solid Coordination Frameworks (SCFs). In this work, a series of six metalloporphyrinic compounds constructed from different meso substituted metalloporphyrins (phenyl, carboxyphenyl and
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Synthetic metalloporphyrin complexes are often used as analogues of natural systems, and they can be used for the preparation of new Solid Coordination Frameworks (SCFs). In this work, a series of six metalloporphyrinic compounds constructed from different meso substituted metalloporphyrins (phenyl, carboxyphenyl and sulfonatophenyl) have been structurally characterized by means of single crystal X-ray diffraction, IR spectroscopy and elemental analysis. The compounds were classified considering the dimensionality of the crystal array, referred just to coordination bonds, into 0D, 1D and 2D compounds. This way, the structural features and relationships of those crystal structures were analyzed, in order to extract conclusions not only about the dimensionality of the networks but also about possible applications of the as-obtained compounds, focusing the interest on the interactions of coordination and crystallization molecules. These interactions provide the coordination bonds and the cohesion forces which produce SCFs with different dimensionalities. Full article
(This article belongs to the Special Issue Metal-Organic Frameworks: Chemistry and Applications)
Open AccessArticle Simultaneous Determination of Five Components in Rat Plasma by UPLC–MS/MS and Its Application to a Comparative Pharmacokinetic Study in Baihe Zhimu Tang and Zhimu Extract
Molecules 2015, 20(4), 6700-6714; doi:10.3390/molecules20046700
Received: 13 January 2015 / Revised: 8 April 2015 / Accepted: 10 April 2015 / Published: 15 April 2015
Cited by 7 | PDF Full-text (1863 KB) | HTML Full-text | XML Full-text
Abstract
Baihe Zhimu Tang (BZT) is a famous traditional Chinese medicine recipe to treat dry coughing due to yin deficiency and for moisturizing the lungs. Zhimu is an essential ingredient in BZT used to treat inflammation, fever and diabetes. The most important active components
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Baihe Zhimu Tang (BZT) is a famous traditional Chinese medicine recipe to treat dry coughing due to yin deficiency and for moisturizing the lungs. Zhimu is an essential ingredient in BZT used to treat inflammation, fever and diabetes. The most important active components in Zhimu are flavonoids such as neomangiferin, mangiferin, and steroid saponins (e.g., timosaponin BII, anemarsaponin BIII, timosaponin AIII). The aim of this study was to compare the pharmacokinetics of mangiferin, neomangiferin, timosaponin BII, anemarsaponin BIII and timosaponin AIII in rat plasma after oral administration of BZT and Zhimu extract (ZME). A sensitive, reliable and robust LC-MS/MS method to simultaneously determine steroid saponins and flavonoids in rat plasma was successfully validated. Significant differences (p < 0.05) were found in the pharmacokinetic parameters of timosaponin BII, anemarsaponin BIII and timosaponin AIII between BZT and ZME. It was surmised that formula compatibility could significantly influence the pharmacokinetics of BZT and our study is the first to study the administration of BZT based on pharmacokinetic studies. Full article
(This article belongs to the collection Bioactive Compounds)
Open AccessArticle Inhibition of Tanshinone IIA, Salvianolic Acid A and Salvianolic Acid B on Areca Nut Extract-Induced Oral Submucous Fibrosis in Vitro
Molecules 2015, 20(4), 6794-6807; doi:10.3390/molecules20046794
Received: 1 February 2015 / Revised: 27 March 2015 / Accepted: 8 April 2015 / Published: 15 April 2015
Cited by 6 | PDF Full-text (2269 KB) | HTML Full-text | XML Full-text
Abstract
Salvia miltiorrhiza Bunge has been reported to possess excellent antifibrotic activity. In this study, we have investigated the effect and mechanism of tanshinone IIA (Tan-IIA), salvianolic acid A (Sal-A) and salvianolic acid B (Sal-B), the important active compounds of Salvia miltiorrhiza Bunge, on
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Salvia miltiorrhiza Bunge has been reported to possess excellent antifibrotic activity. In this study, we have investigated the effect and mechanism of tanshinone IIA (Tan-IIA), salvianolic acid A (Sal-A) and salvianolic acid B (Sal-B), the important active compounds of Salvia miltiorrhiza Bunge, on areca nut extract (ANE)-induced oral submucous fibrosis (OSF) in vitro. Through human procollagen gene promoter luciferase reporter plasmid assay, hydroxyproline assay, gelatin zymography assay, qRT-PCR, ELISA and Western blot assay, the influence of these three compounds on ANE-stimulated cell viability, collagen accumulation, procollagen gene transcription, MMP-2/-9 activity, MMP-1/-13 and TIMP-1/-2 expression, cytokine secretion and the activation of PI3K/AKT, ERK/JNK/p38 MAPK and TGF-β/Smads pathways were detected. The results showed that Tan-IIA, Sal-A and Sal-B could significantly inhibit the ANE-stimulated abnormal viability and collagen accumulation of mice oral mucosal fibroblasts (MOMFs), inhibit the transcription of procollagen gene COL1A1 and COL3A1, increase MMP-2/-9 activity, decrease TIMP-1/-2 expression and inhibit the transcription and release of CTGF, TGF-β1, IL-6 and TNF-α; Tan-IIA, Sal-A and Sal-B also inhibited the ANE-induced activation of AKT and ERK MAPK pathways in MOMFs and the activation of TGF-β/Smads pathway in HaCaT cells. In conclusion, Tan-IIA, Sal-A and Sal-B possess excellent antifibrotic activity in vitro and can possibly be used to promote the rehabilitation of OSF patients. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Synthesis and Pharmacophore Modelling of 2,6,9-Trisubstituted Purine Derivatives and Their Potential Role as Apoptosis-Inducing Agents in Cancer Cell Lines
Molecules 2015, 20(4), 6808-6826; doi:10.3390/molecules20046808
Received: 4 March 2015 / Revised: 9 April 2015 / Accepted: 10 April 2015 / Published: 15 April 2015
Cited by 6 | PDF Full-text (978 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A series of 2,6,9-trisubstituted purine derivatives have been synthesized and investigated for their potential role as antitumor agents. Twelve compounds were obtained by a three step synthetic procedure using microwave irradiation in a pivotal step. All compounds were evaluated in vitro to determine
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A series of 2,6,9-trisubstituted purine derivatives have been synthesized and investigated for their potential role as antitumor agents. Twelve compounds were obtained by a three step synthetic procedure using microwave irradiation in a pivotal step. All compounds were evaluated in vitro to determine their potential effect on cell toxicity by the MTT method and flow cytometry analysis on four cancer cells lines and Vero cells. Three out of twelve compounds were found to be promising agents compared to a known and effective anticancer drug, etoposide, in three out of four cancer cell lines assayed with considerable selectivity. Preliminary flow cytometry data suggests that compounds mentioned above induce apoptosis on these cells. The main structural requirements for their activity for each cancer cell line were characterized with a preliminary pharmacophore model, which identified aromatic centers, hydrogen acceptor/donor center and a hydrophobic area. These features were consistent with the cytotoxic activity of the assayed compounds. Full article
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Open AccessArticle Synthesis of 5-Alkoxythieno[2,3-e][1,2,4]triazolo[4,3-c]pyrimidine Derivatives and Evaluation of Their Anticonvulsant Activities
Molecules 2015, 20(4), 6827-6843; doi:10.3390/molecules20046827
Received: 12 March 2015 / Revised: 2 April 2015 / Accepted: 8 April 2015 / Published: 15 April 2015
Cited by 3 | PDF Full-text (850 KB) | HTML Full-text | XML Full-text
Abstract
This work concerns the design and synthesis of novel, substituted 5-alkoxythieno[2,3-e][1,2,4]triazolo[4,3-c]pyrimidine derivatives 5ap prepared from 3-amino-2-thiophenecarboxylic acid methyl ester. The final compounds were screened for their in vivo anticonvulsant activity using maximal electroshock (MES) and subcutaneous pentylenetetrazole
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This work concerns the design and synthesis of novel, substituted 5-alkoxythieno[2,3-e][1,2,4]triazolo[4,3-c]pyrimidine derivatives 5ap prepared from 3-amino-2-thiophenecarboxylic acid methyl ester. The final compounds were screened for their in vivo anticonvulsant activity using maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) tests. Neurotoxicity (NT) was tested using a rotarod test. The structure-anticonvulsant activity relationship analysis revealed that the most effective structural motif involves a substituted phenol, especially when substituted with a single chlorine, fluorine or trifluoromethyl group (at the meta-position), or two chlorine atoms. These molecules possessed high activity according to the MES and scPTZ models. Quantitative assessment of the compounds after intraperitoneal administration in mice showed that the most active compound was 5-[3-(trifluoromethyl)phenoxy]thieno[2,3-e] [1,2,4]triazolo[4,3-c]pyrimidine (5o) with ED50 values of 11.5 mg/kg (MES) and 58.9 mg/kg (scPTZ). Furthermore, compound 5o was more effective in the MES and scPTZ tests than the well-known anticonvulsant drugs carbamazepine and ethosuximide. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Phytochemicals and Estrogen-Receptor Agonists from the Aerial Parts of Liriope platyphylla
Molecules 2015, 20(4), 6844-6855; doi:10.3390/molecules20046844
Received: 13 March 2015 / Revised: 12 April 2015 / Accepted: 13 April 2015 / Published: 16 April 2015
Cited by 5 | PDF Full-text (2768 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
One new benzofuran, (2R)-(2',4'-dihydroxybenzyl)-6,7-methylenedioxy-2,3-dihydrobenzofuran (1), one new phenylisocoumarin, 3-(2'-hydroxyphenyl)-6,8-dihydroxy-7-methoxy-isocoumarin (2), and one new benzofuroisocoumarin, platyphyllarin C (3), were isolated from the ethanolic extract of Liriope platyphylla aerial parts, along with seventeen known compounds. The structures
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One new benzofuran, (2R)-(2',4'-dihydroxybenzyl)-6,7-methylenedioxy-2,3-dihydrobenzofuran (1), one new phenylisocoumarin, 3-(2'-hydroxyphenyl)-6,8-dihydroxy-7-methoxy-isocoumarin (2), and one new benzofuroisocoumarin, platyphyllarin C (3), were isolated from the ethanolic extract of Liriope platyphylla aerial parts, along with seventeen known compounds. The structures of the isolates were established by spectroscopic analysis and comparison with the literature data. The results indicated that structures 1–3 are uncommon in Nature. Benzofuroisocoumarin 4, flavonoids 9, 10, and 1315, and homoisoflavonoids 19 and 20 exhibited significant binding activity to estrogen-receptor α and/or β as demonstrated by the SEAP reporter assay system in an MCF-7 cell-line. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Efficient Synthesis of Readily Water-Soluble Sulfonic Acid Carbamates
Molecules 2015, 20(4), 6856-6865; doi:10.3390/molecules20046856
Received: 10 March 2015 / Revised: 5 April 2015 / Accepted: 8 April 2015 / Published: 16 April 2015
PDF Full-text (677 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A series of various readily water-soluble carbamates were synthesized with good yields. These compounds are useful chemical tracers for assessing the cooling progress in a georeservoir during geothermal power plant operation. Acylation of primary amines was carried out as well as using a
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A series of various readily water-soluble carbamates were synthesized with good yields. These compounds are useful chemical tracers for assessing the cooling progress in a georeservoir during geothermal power plant operation. Acylation of primary amines was carried out as well as using a solution of sodium bicarbonate and without the presence of salt. Products were characterized by 1H-NMR and 13C-NMR. Purity was confirmed through elemental analysis. Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessArticle Anti-Inflammatory Effect of Wogonin on RAW 264.7 Mouse Macrophages Induced with Polyinosinic-Polycytidylic Acid
Molecules 2015, 20(4), 6888-6900; doi:10.3390/molecules20046888
Received: 21 February 2015 / Revised: 6 April 2015 / Accepted: 10 April 2015 / Published: 16 April 2015
Cited by 16 | PDF Full-text (771 KB) | HTML Full-text | XML Full-text
Abstract
Wogonin (5,7-dihydroxy-8-methoxyflavone) is an active flavonoid compound originally isolated from Scutellaria radix, which has been used to treat lung inflammation in Korea, China, and Japan. Wogonin has been known to inhibit inducible nitric oxide synthase and have the anti-tumor properties. However, the
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Wogonin (5,7-dihydroxy-8-methoxyflavone) is an active flavonoid compound originally isolated from Scutellaria radix, which has been used to treat lung inflammation in Korea, China, and Japan. Wogonin has been known to inhibit inducible nitric oxide synthase and have the anti-tumor properties. However, the effects of wogonin on virus-induced macrophages are not fully reported. In this study, the anti-inflammatory effect of wogonin on double-stranded RNA (dsRNA)-induced macrophages was examined. Wogonin restored the cell viability in dsRNA [polyinosinic-polycytidylic acid]-induced RAW 264.7 mouse macrophages at concentrations of up to 50 μM. Wogonin significantly inhibited the production of nitric oxide, IL-1α, IL-1β, IL-6, IL-10, IP-10, G-CSF, GM-CSF, LIF (IL-6 class cytokine), LIX/CXCL5, MCP-1, M-CSF, MIP-1α, MIP-1β, MIP-2, RANTES/CCL5, TNF-α, and VEGF as well as calcium release and mRNA expression of signal transducer and activated transcription 1 (STAT1) and STAT3 in dsRNA-induced RAW 264.7 cells (P < 0.05). In conclusion, wogonin has anti-inflammatory properties related with its inhibition of nitric oxide, cytokines, chemokines, and growth factors in dsRNA-induced macrophages via the calcium-STAT pathway. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Simultaneous Quantification of Diazepam and Dexamethasone in Plasma by High-Performance Liquid Chromatography with Tandem Mass Spectrometry and Its Application to a Pharmacokinetic Comparison between Normoxic and Hypoxic Rats
Molecules 2015, 20(4), 6901-6912; doi:10.3390/molecules20046901
Received: 13 February 2015 / Revised: 7 April 2015 / Accepted: 13 April 2015 / Published: 16 April 2015
Cited by 6 | PDF Full-text (938 KB) | HTML Full-text | XML Full-text
Abstract
In order to investigate the pharmacokinetics of a combination of diazepam and dexamethasone under hypoxic conditions, a novel, sensitive and specific liquid chromatography with tandem mass spectrometry (LC-MS/MS) method for the simultaneous determination of diazepam and dexamethasone in rat plasma was developed and
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In order to investigate the pharmacokinetics of a combination of diazepam and dexamethasone under hypoxic conditions, a novel, sensitive and specific liquid chromatography with tandem mass spectrometry (LC-MS/MS) method for the simultaneous determination of diazepam and dexamethasone in rat plasma was developed and validated. The chromatographic separation of analytes was successfully achieved on an XTerra® MS C18 column using a gradient elution of methanol and water containing 0.1% formic acid at a flow rate of 0.5 mL/min. This method demonstrated good linearity and no endogenous material interferences. The linear ranges were 1.0–100 ng/mL for diazepam and 2.0–200 ng/mL for dexamethasone. The intra- and inter-day precision for the two compounds in plasma were lower than 10.0%, and the accuracy was between −7.9% and 11.5%. Our method was then successfully applied in a pharmacokinetic comparison between normoxic and hypoxic rats. The results indicated that there were significant differences in the main pharmacokinetics parameters of diazepam and dexamethasone between normoxic and hypoxic rats. The results provide the important and valuable information for discovering and developing novel anti-hypoxia drug combinations, as well as a better understanding of the safety and efficacy of these drugs. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Accumulation of GD1α Ganglioside in MDA-MB-231 Breast Cancer Cells Expressing ST6GalNAc V
Molecules 2015, 20(4), 6913-6924; doi:10.3390/molecules20046913
Received: 14 January 2015 / Revised: 9 April 2015 / Accepted: 14 April 2015 / Published: 16 April 2015
Cited by 4 | PDF Full-text (3807 KB) | HTML Full-text | XML Full-text
Abstract
α-Series gangliosides define a particular sub-class of glycosphingolipids containing sialic acid α2,6-linked to GalNAc residue that was isolated as a minor compound from the brain. The sialyltransferase ST6GalNAc V was cloned from mouse brain and showed α2,6-sialyltransferase activity almost exclusively for GM1b
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α-Series gangliosides define a particular sub-class of glycosphingolipids containing sialic acid α2,6-linked to GalNAc residue that was isolated as a minor compound from the brain. The sialyltransferase ST6GalNAc V was cloned from mouse brain and showed α2,6-sialyltransferase activity almost exclusively for GM1b, to form GD1α and is considered as the main enzyme involved in the biosynthesis of α-series gangliosides. Recently, ST6GALNAC5 was identified as one of the genes over-expressed in breast cancer cell populations selected for their ability to produce brain metastasis. However, the capacity of human breast cancer cells to produce α-series gangliosides has never been clearly demonstrated. Here, we show by stable transfection and MS-MS analysis of total glycosphingolipids that ST6GALNAC5 expressing MDA-MB-231 breast cancer cells accumulate GD1α ganglioside (IV3Neu5Ac1, III6Neu5Ac1Gg4-Cer). Full article
(This article belongs to the collection Advances in Carbohydrate Chemistry)
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Open AccessArticle Identification of the Chemical Constituents in Aqueous Extract of Zhi-Qiao and Evaluation of Its Antidepressant Effect
Molecules 2015, 20(4), 6925-6940; doi:10.3390/molecules20046925
Received: 30 January 2015 / Revised: 10 April 2015 / Accepted: 14 April 2015 / Published: 16 April 2015
Cited by 11 | PDF Full-text (1250 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The immature fruit of Citrus aurantium L. (Zhi-Qiao, ZQ) has been used as a traditional medicine in China. Our previous study has shown that ZQ decoction may contribute to the antidepressant-like action of Chaihu-Shu-Gan-San. However, there are no reports on the chemical constituents
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The immature fruit of Citrus aurantium L. (Zhi-Qiao, ZQ) has been used as a traditional medicine in China. Our previous study has shown that ZQ decoction may contribute to the antidepressant-like action of Chaihu-Shu-Gan-San. However, there are no reports on the chemical constituents of ZQ aqueous extract or its anti-depression effects. Firstly, this research reported the on-line identification of the chemical constituents in the aqueous extract of ZQ by coupling ultra-performance liquid chromatography/time-of-flight mass spectrometry (UPLC-Q-TOF/MS). A total of 31 chemical constituents were identified in ZQ aqueous extract, including one tannic acid, five flavones, 13 flavanones, one limonoid, three coumarins, three cyclic peptides, and five polymethoxylated flavonoids. The antidepressant effect of ZQ aqueous extract was evaluated in vivo and the results indicated that the mice immobility time during the forced swimming test and the tail suspension test were significantly reduced with ZQ treatment. MTT assays showed both ZQ aqueous extract and its major constituents (naringin, hesperidin, neohesperidin, and nobiletin) had neuroprotective effect on corticosterone-induced neurotoxicity in PC12 cells. The in vivo and in vitro results suggest that ZQ has an antidepressant effect. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle NKCS, a Mutant of the NK-2 Peptide, Causes Severe Distortions and Perforations in Bacterial, But Not Human Model Lipid Membranes
Molecules 2015, 20(4), 6941-6958; doi:10.3390/molecules20046941
Received: 30 January 2015 / Revised: 9 April 2015 / Accepted: 10 April 2015 / Published: 16 April 2015
Cited by 1 | PDF Full-text (3095 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
NKCS is an improved mutant of the bioactive peptide NK-2, which shows strong activity against Escherichia coli and low toxicity towards human cells. The different activity demonstrates the relevance of the physico-chemical nature of the target membrane for the biological effect of this
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NKCS is an improved mutant of the bioactive peptide NK-2, which shows strong activity against Escherichia coli and low toxicity towards human cells. The different activity demonstrates the relevance of the physico-chemical nature of the target membrane for the biological effect of this peptide. We studied the effect of this potent antimicrobial peptide on model membranes by activity studies, differential scanning calorimetry, single molecule tracking and tracer efflux experiments. We found that NKCS severely distorted, penetrated and perforated model lipid membranes that resembled bacterial membranes, but not those that were similar to human cell membranes. The interactions of NKCS with phosphatidylethanolamine, which is abundant in bacterial membranes, were especially strong and are probably responsible for its antimicrobial activity. Full article
(This article belongs to the Special Issue Cell Penetrating Peptides (CPPs))
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Open AccessArticle Alkylamides of Acmella oleracea
Molecules 2015, 20(4), 6970-6977; doi:10.3390/molecules20046970
Received: 10 February 2015 / Revised: 25 March 2015 / Accepted: 8 April 2015 / Published: 16 April 2015
Cited by 3 | PDF Full-text (800 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Phytochemical investigation of the flowers of Acmella oleracea had resulted in the isolation of one new alkylamide, (2E,5Z)-N-isobutylundeca-2,5-diene-8,10-diynamide (1), together with four known analogues (2-5). The structures of these compounds were
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Phytochemical investigation of the flowers of Acmella oleracea had resulted in the isolation of one new alkylamide, (2E,5Z)-N-isobutylundeca-2,5-diene-8,10-diynamide (1), together with four known analogues (2-5). The structures of these compounds were determined by the interpretation of spectroscopic methods, especially NMR technologies (COSY, HSQC, HMBC, and NOESY). In addition, a convenient method for concentrating the alkylamide-rich fraction and analyzing fingerprint profile of A. oleracea was established. Full article
(This article belongs to the collection Bioactive Compounds)
Open AccessArticle Discovery of Metal Ions Chelator Quercetin Derivatives with Potent Anti-HCV Activities
Molecules 2015, 20(4), 6978-6999; doi:10.3390/molecules20046978
Received: 3 March 2015 / Revised: 8 April 2015 / Accepted: 13 April 2015 / Published: 16 April 2015
PDF Full-text (780 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Analogues or isosteres of α,γ-diketoacid (DKA) 1a show potent inhibition of hepatitis C virus (HCV) NS5B polymerase through chelation of the two magnesium ions at the active site. The anti-HCV activity of the flavonoid quercetin (2) could partly be attributed to
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Analogues or isosteres of α,γ-diketoacid (DKA) 1a show potent inhibition of hepatitis C virus (HCV) NS5B polymerase through chelation of the two magnesium ions at the active site. The anti-HCV activity of the flavonoid quercetin (2) could partly be attributed to it being a structural mimic of DKAs. In order to delineate the structural features required for the inhibitory effect and improve the anti-HCV potency, two novel types of quercetin analogues, 7-O-arylmethylquercetins and quercetin-3-O-benzoic acid esters, were designed, synthesized and evaluated for their anti-HCV properties in cell-based assays. Among the 38 newly synthesized compounds, 7-O-substituted derivative 3i and 3-O-substituted derivative 4f were found to be the most active in the corresponding series (EC50 = 3.8 μM and 9.0 μΜ, respectively). Docking studies suggested that the quercetin analogues are capable of establishing key coordination with the two magnesium ions as well as interactions with residues at the active site of HCV NS5B. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Chilean Prosopis Mesocarp Flour: Phenolic Profiling and Antioxidant Activity
Molecules 2015, 20(4), 7017-7033; doi:10.3390/molecules20047017
Received: 18 January 2015 / Revised: 9 April 2015 / Accepted: 13 April 2015 / Published: 17 April 2015
Cited by 4 | PDF Full-text (2175 KB) | HTML Full-text | XML Full-text
Abstract
In South America, the mesocarp flour of Prosopis species plays a prominent role as a food resource in arid areas. The aim of this work was the characterization of the phenolic antioxidants occurring in the pod mesocarp flour of Chilean Prosopis. Samples
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In South America, the mesocarp flour of Prosopis species plays a prominent role as a food resource in arid areas. The aim of this work was the characterization of the phenolic antioxidants occurring in the pod mesocarp flour of Chilean Prosopis. Samples were collected in the Copiapo, Huasco and Elqui valleys from the north of Chile. The samples of P. chilensis flour exhibited a total phenolic content ranging between 0.82–2.57 g gallic acid equivalents/100 g fresh flour weight. The highest antioxidant activity, measured by the DPPH assay, was observed for samples from the Huasco valley. HPLC-MS/MS analysis allowed the tentative identification of eight anthocyanins and 13 phenolic compounds including flavonol glycosides, C-glycosyl flavones and ellagic acid derivatives. The antioxidant activity and the phenolic composition in the flour suggest that this ancient South American resource may have potential as a functional food. Full article
(This article belongs to the Section Molecular Diversity)
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Open AccessArticle Phytochemical Compositions and Biological Activities of Essential Oil from Xanthium strumarium L.
Molecules 2015, 20(4), 7034-7047; doi:10.3390/molecules20047034
Received: 5 February 2015 / Revised: 13 April 2015 / Accepted: 14 April 2015 / Published: 17 April 2015
Cited by 23 | PDF Full-text (741 KB) | HTML Full-text | XML Full-text
Abstract
The chemical composition of the essential oil (EO) from fresh cocklebur (Xanthium strumarium L.) leaves was investigated by GC-MS. The antimicrobial activity of the EO was tested against Gram-positive and Gram-negative bacteria and fungi. Scolicidal activity was assayed against Echinococcus granulosus protoscolices.
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The chemical composition of the essential oil (EO) from fresh cocklebur (Xanthium strumarium L.) leaves was investigated by GC-MS. The antimicrobial activity of the EO was tested against Gram-positive and Gram-negative bacteria and fungi. Scolicidal activity was assayed against Echinococcus granulosus protoscolices. In total, 34 compounds were identified, accounting for 98.96% of the EO. The main compounds in the EO were cis-β-guaiene (34.2%), limonene (20.3%), borneol (11.6%), bornyl acetate (4.5%), β-cubebene (3.8%), sabinene (3.6%), phytol (3.1%), β-selinene (2.8%), camphene (2.2%), α-cubebene (2.4%), β-caryophyllene (1.9%), α-pinene (1.8%) and xanthinin (1.04%). The antibacterial and antifungal screening of the EO showed that all assayed concentrations significantly inhibited the growth of Staphylococcus aureus, Bacillus subtilis, Klebsiella pneumoniae, Pseudomonas aeruginosa, Candida albicans and Aspergillus niger (MIC = 0.5 ± 0.1, 1.3 ± 0.0, 4.8 ± 0.0, 20.5 ± 0.3, 55.2 ± 0.0 and 34.3 ± 0.0 µg/mL, respectively). The scolicidal assay indicated that the EO exhibited a significant activity against E. granulosus protoscolices. To the best of our knowledge, this is the first report on the scolicidal activity of X. strumarium. Because of the emergence of antimicrobial drug resistance, the study of new effective natural chemotherapeutic agents, such as the X. strumarium EO, possibly with low side effects, represents a very promising approach in biomedical research. Full article
Open AccessArticle Preparative Isolation and Purification of Lignans from Justicia procumbens Using High-Speed Counter-Current Chromatography in Stepwise Elution Mode
Molecules 2015, 20(4), 7048-7058; doi:10.3390/molecules20047048
Received: 8 March 2015 / Revised: 3 April 2015 / Accepted: 8 April 2015 / Published: 20 April 2015
Cited by 4 | PDF Full-text (743 KB) | HTML Full-text | XML Full-text
Abstract
Lignans, which are recognized as main constituents in Justicia procumbens, have attracted considerable attention due to their pharmacological activities, including antitumor, anti-hepatitic, cytotoxic, anti-microbial, and anti-virus properties. Preparative high-speed counter-current chromatography (HSCCC) was successfully applied to the isolation and purification of four
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Lignans, which are recognized as main constituents in Justicia procumbens, have attracted considerable attention due to their pharmacological activities, including antitumor, anti-hepatitic, cytotoxic, anti-microbial, and anti-virus properties. Preparative high-speed counter-current chromatography (HSCCC) was successfully applied to the isolation and purification of four lignans (justicidin B (1), justicidin A (2), 6'-hydroxyjusticidin C (3) and lignan J1 (4)) from J. procumbens using stepwise elution with a pair of two-phase solvent systems composed of n-hexane–ethyl acetate–methanol–water at (1.3:1:1.3:1, v/v) and (2.5:1:2.5:1, v/v). The preparative HSCCC separation was performed on 300 mg of crude sample yielding compounds 1 (19.7 mg), 2 (9.86 mg), 3 (11.26 mg), and 4 (2.54 mg) in a one-step separation, with purities over 95% as determined by HPLC. The structures of these compounds were identified by MS, 1H-NMR and 13C-NMR. This is the first report on the application of HSCCC to the efficient separation of lignans from J. procumbens. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Glycodendrimers and Modified ELISAs: Tools to Elucidate Multivalent Interactions of Galectins 1 and 3
Molecules 2015, 20(4), 7059-7096; doi:10.3390/molecules20047059
Received: 5 March 2015 / Revised: 29 March 2015 / Accepted: 1 April 2015 / Published: 20 April 2015
Cited by 4 | PDF Full-text (2718 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Multivalent protein-carbohydrate interactions that are mediated by sugar-binding proteins, i.e., lectins, have been implicated in a myriad of intercellular recognition processes associated with tumor progression such as galectin-mediated cancer cellular migration/metastatic processes. Here, using a modified ELISA, we show that glycodendrimers bearing
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Multivalent protein-carbohydrate interactions that are mediated by sugar-binding proteins, i.e., lectins, have been implicated in a myriad of intercellular recognition processes associated with tumor progression such as galectin-mediated cancer cellular migration/metastatic processes. Here, using a modified ELISA, we show that glycodendrimers bearing mixtures of galactosides, lactosides, and N-acetylgalactosaminosides, galectin-3 ligands, multivalently affect galectin-3 functions. We further demonstrate that lactose functionalized glycodendrimers multivalently bind a different member of the galectin family, i.e., galectin-1. In a modified ELISA, galectin-3 recruitment by glycodendrimers was shown to directly depend on the ratio of low to high affinity ligands on the dendrimers, with lactose-functionalized dendrimers having the highest activity and also binding well to galectin-1. The results depicted here indicate that synthetic multivalent systems and upfront assay formats will improve the understanding of the multivalent function of galectins during multivalent protein carbohydrate recognition/interaction. Full article
(This article belongs to the Special Issue Protein-Carbohydrate Interactions, and Beyond)
Open AccessArticle Inhibition of Oxidative Stress and Skin Aging-Related Enzymes by Prenylated Chalcones and Other Flavonoids from Helichrysum teretifolium
Molecules 2015, 20(4), 7143-7155; doi:10.3390/molecules20047143
Received: 8 March 2015 / Revised: 9 April 2015 / Accepted: 14 April 2015 / Published: 20 April 2015
Cited by 10 | PDF Full-text (736 KB) | HTML Full-text | XML Full-text
Abstract
Ten flavonoid-related structures viz. heliteretifolin (1), isoxanthohumol (2), 2',4',6'-trihydroxy-3'-prenylchalcone (3), isoglabranin (4), glabranin (5), 7-methoxy-isoglabranin (6), quercetin (7), 4'-methoxyquercetin (8), 4'-methoxykaempferol (9) and mosloflavone (
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Ten flavonoid-related structures viz. heliteretifolin (1), isoxanthohumol (2), 2',4',6'-trihydroxy-3'-prenylchalcone (3), isoglabranin (4), glabranin (5), 7-methoxy-isoglabranin (6), quercetin (7), 4'-methoxyquercetin (8), 4'-methoxykaempferol (9) and mosloflavone (10) were isolated from a H. teretifolium methanolic extract and identified. One of them (compound 1) is reported for the first time from a natural source, while compounds 6, 810 were isolated for the first time from the genus Helichrysum. The total extract of H. teretifolium showed potent antioxidant activity. When tested for total antioxidant capacity compound 3 possesses moderate biological activity compared to 2, which displayed some of the highest TEAC values (4529.01 ± 2.44; 4170.66 ± 6.72) µM TE/g, respectively. Compounds 7 and 8 demonstrated the highest inhibitory activities on Fe2+-induced lipid peroxidation (IC50 = 2.931; 6.449 µg/mL); tyrosinase (8.092; 27.573) and elastase (43.342; 86.548). Additionally, the total antioxidant capacities measured as FRAP (4816.31 ± 7.42; 3584.17 ± 0.54) µM AAE/g, and ORAC for hydroxyl radical (7.265 ± 0.71; 6.779 ± 3.40) × 106 and peroxyl radical (17.836 ± 2.90; 12.545 ± 5.07) × 103 µM TE/g were also observed for compounds 7 and 8, respectively. In conclusion, H. teretifolium total extract represents a rich source of bioactive constituents with potent antioxidant and moderate anti-tyrosinase and anti-elastase activities that can help to avert accumulation of free radicals in the body, and could therefore be good candidates for the prevention and/or treatment of skin-related conditions, such as aging. This is the first scientific report on the chemical and biological profile of H. teretifolium. Full article
(This article belongs to the collection Bioactive Compounds)
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Open AccessArticle Characterization of a (2R,3R)-2,3-Butanediol Dehydrogenase from Rhodococcus erythropolis WZ010
Molecules 2015, 20(4), 7156-7173; doi:10.3390/molecules20047156
Received: 12 March 2015 / Revised: 13 April 2015 / Accepted: 14 April 2015 / Published: 20 April 2015
Cited by 5 | PDF Full-text (1915 KB) | HTML Full-text | XML Full-text
Abstract
The gene encoding a (2R,3R)-2,3-butanediol dehydrogenase from Rhodococcus erythropolis WZ010 (ReBDH) was over-expressed in Escherichia coli and the resulting recombinant ReBDH was successfully purified by Ni-affinity chromatography. The purified ReBDH in the native form was found to exist as
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The gene encoding a (2R,3R)-2,3-butanediol dehydrogenase from Rhodococcus erythropolis WZ010 (ReBDH) was over-expressed in Escherichia coli and the resulting recombinant ReBDH was successfully purified by Ni-affinity chromatography. The purified ReBDH in the native form was found to exist as a monomer with a calculated subunit size of 37180, belonging to the family of the zinc-containing alcohol dehydrogenases. The enzyme was NAD(H)-specific and its optimal activity for acetoin reduction was observed at pH 6.5 and 55 °C. The optimal pH and temperature for 2,3-butanediol oxidation were pH 10 and 45 °C, respectively. The enzyme activity was inhibited by ethylenediaminetetraacetic acid (EDTA) or metal ions Al3+, Zn2+, Fe2+, Cu2+ and Ag+, while the addition of 10% (v/v) dimethyl sulfoxide (DMSO) in the reaction mixture increased the activity by 161.2%. Kinetic parameters of the enzyme showed lower Km values and higher catalytic efficiency for diacetyl and NADH in comparison to those for (2R,3R)-2,3-butanediol and NAD+. The activity of acetoin reduction was 7.7 times higher than that of (2R,3R)-2,3-butanediol oxidation when ReBDH was assayed at pH 7.0, suggesting that ReBDH-catalyzed reaction in vivo might favor (2R,3R)-2,3-butanediol formation rather than (2R,3R)-2,3-butanediol oxidation. The enzyme displayed absolute stereospecificity in the reduction of diacetyl to (2R,3R)-2,3-butanediol via (R)-acetoin, demonstrating its potential application on the synthesis of (R)-chiral alcohols. Full article
(This article belongs to the Special Issue Enzyme-Catalyzed Reactions)
Open AccessArticle Synthesis and Antiplatelet Activity of Antithrombotic Thiourea Compounds: Biological and Structure-Activity Relationship Studies
Molecules 2015, 20(4), 7174-7200; doi:10.3390/molecules20047174
Received: 27 February 2015 / Revised: 8 April 2015 / Accepted: 13 April 2015 / Published: 20 April 2015
Cited by 5 | PDF Full-text (3703 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The incidence of hematological disorders has increased steadily in Western countries despite the advances in drug development. The high expression of the multi-resistance protein 4 in patients with transitory aspirin resistance, points to the importance of finding new molecules, including those that are
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The incidence of hematological disorders has increased steadily in Western countries despite the advances in drug development. The high expression of the multi-resistance protein 4 in patients with transitory aspirin resistance, points to the importance of finding new molecules, including those that are not affected by these proteins. In this work, we describe the synthesis and biological evaluation of a series of N,N'-disubstituted thioureas derivatives using in vitro and in silico approaches. New designed compounds inhibit the arachidonic acid pathway in human platelets. The most active thioureas (compounds 3d, 3i, 3m and 3p) displayed IC50 values ranging from 29 to 84 µM with direct influence over in vitro PGE2 and TXA2 formation. In silico evaluation of these compounds suggests that direct blockage of the tyrosyl-radical at the COX-1 active site is achieved by strong hydrophobic contacts as well as electrostatic interactions. A low toxicity profile of this series was observed through hemolytic, genotoxic and mutagenic assays. The most active thioureas were able to reduce both PGE2 and TXB2 production in human platelets, suggesting a direct inhibition of COX-1. These results reinforce their promising profile as lead antiplatelet agents for further in vivo experimental investigations. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Evaluation of New Dihydrophthalazine-Appended 2,4-Diaminopyrimidines against Bacillus anthracis: Improved Syntheses Using a New Pincer Complex
Molecules 2015, 20(4), 7222-7244; doi:10.3390/molecules20047222
Received: 20 March 2015 / Revised: 14 April 2015 / Accepted: 15 April 2015 / Published: 21 April 2015
Cited by 3 | PDF Full-text (1999 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The synthesis and evaluation of ten new dihydrophthalazine-appended 2,4-diaminopyrimidines as potential drugs to treat Bacillus anthracis is reported. An improved synthesis utilizing a new pincer catalyst, dichlorobis[1-(dicyclohexylphosphanyl)-piperidine]palladium(II), allows the final Heck coupling to be performed at 90 °C using triethylamine as the base.
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The synthesis and evaluation of ten new dihydrophthalazine-appended 2,4-diaminopyrimidines as potential drugs to treat Bacillus anthracis is reported. An improved synthesis utilizing a new pincer catalyst, dichlorobis[1-(dicyclohexylphosphanyl)-piperidine]palladium(II), allows the final Heck coupling to be performed at 90 °C using triethylamine as the base. These milder conditions have been used to achieve improved yields for new and previously reported substrates with functional groups that degrade or react at the normal 140 °C reaction temperature. An analytical protocol for separating the S and R enantiomers of two of the most active compounds is also disclosed. Finally, the X-ray structure for the most active enantiomer of the lead compound, (S)-RAB1, is given. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Diterpenes Synthesized from the Natural Serrulatane Leubethanol and Their in Vitro Activities against Mycobacterium tuberculosis
Molecules 2015, 20(4), 7245-7262; doi:10.3390/molecules20047245
Received: 2 February 2015 / Revised: 30 March 2015 / Accepted: 13 April 2015 / Published: 21 April 2015
Cited by 4 | PDF Full-text (805 KB) | HTML Full-text | XML Full-text
Abstract
Seventeen new derivatives of the natural diterpene leubethanol, including some potential pro-drugs, with changes in the functionality of the aliphatic chain or modifications of aromatic ring and the phenolic group, were synthesized and tested in vitro by the MABA technique for their activity
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Seventeen new derivatives of the natural diterpene leubethanol, including some potential pro-drugs, with changes in the functionality of the aliphatic chain or modifications of aromatic ring and the phenolic group, were synthesized and tested in vitro by the MABA technique for their activity against the H37Rv strain of Mycobacterium tuberculosis. Some compounds showed antimycobacterial selectivity indices higher than leubethanol. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Bifunctionalized Allenes. Part XVI. Synthesis of 3-Phosphoryl-2,5-dihydrofurans by Coinage Metal-Catalyzed Cyclo-isomerization of Phosphorylated α-Hydroxyallenes
Molecules 2015, 20(4), 7263-7275; doi:10.3390/molecules20047263
Received: 23 March 2015 / Revised: 15 April 2015 / Accepted: 17 April 2015 / Published: 21 April 2015
Cited by 4 | PDF Full-text (733 KB) | HTML Full-text | XML Full-text
Abstract
Phosphorylated α-hydroxyallenes 1 and 2 were smoothly converted into the corresponding 2,5-dihydrofurans 3 and 4 in an 5-endo-trig cycloisomerization reaction by using 5 mol % of coinage metal salts as catalyst. Experimental conditions such as the type of the solvent, the reaction
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Phosphorylated α-hydroxyallenes 1 and 2 were smoothly converted into the corresponding 2,5-dihydrofurans 3 and 4 in an 5-endo-trig cycloisomerization reaction by using 5 mol % of coinage metal salts as catalyst. Experimental conditions such as the type of the solvent, the reaction temperature, the mol % and the type of the catalyst were optimized. This mild and efficient cyclization method can be applied to dimethyl 1-hydroxyalkyl-alka-1,2-dienephosphonates 1 and 2-diphenylphosphinoyl-2,3-dien-1-ols 2ac and 3-diphenylphosphinoyl-3,4-dien-2-ols 2d,e, furnishing 3-phosphorylated 2,5-dihydrofurans 3 and 4 in very good yields. Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessArticle Photorelease of Pyridyl Esters in Organometallic Ru(II) Arene Complexes
Molecules 2015, 20(4), 7276-7291; doi:10.3390/molecules20047276
Received: 20 February 2015 / Revised: 14 April 2015 / Accepted: 15 April 2015 / Published: 21 April 2015
Cited by 7 | PDF Full-text (2581 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
New Ru(II) arene complexes of formula [(η6-p-cym)Ru(N-N)(X)]2+ (where p-cym = para-cymene, N-N = 2,2'-bipyrimidine (bpm) or 2,2'-bipyridine (bpy) and X = m/p-COOMe-Py, 14) were synthesised and characterized, including the molecular structure
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New Ru(II) arene complexes of formula [(η6-p-cym)Ru(N-N)(X)]2+ (where p-cym = para-cymene, N-N = 2,2'-bipyrimidine (bpm) or 2,2'-bipyridine (bpy) and X = m/p-COOMe-Py, 14) were synthesised and characterized, including the molecular structure of complexes [(η6-p-cym)Ru(bpy)(m-COOMe-Py)]2+ (3) and [(η6-p-cym)Ru(bpy) (p-COOMe-Py)]2+ (4) by single-crystal X-ray diffraction. Complexes 14 are stable in the dark in aqueous solution over 48 h and photolysis studies indicate that they can photodissociate the monodentate m/p-COOMe-Py ligands selectively with yields lower than 1%. DFT and TD-DFT calculations (B3LYP/LanL2DZ/6-31G**) performed on singlet and triplet states pinpoint a low-energy triplet state as the reactive state responsible for the selective dissociation of the monodentate pyridyl ligands. Full article
(This article belongs to the Special Issue Practical Applications of Metal Complexes)
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Open AccessArticle Evaluation of Novel Antibacterial N-Halamine Nanoparticles Prodrugs towards Susceptibility of Escherichia coli Induced by DksA Protein
Molecules 2015, 20(4), 7292-7308; doi:10.3390/molecules20047292
Received: 12 March 2015 / Revised: 3 April 2015 / Accepted: 7 April 2015 / Published: 21 April 2015
Cited by 4 | PDF Full-text (3664 KB) | HTML Full-text | XML Full-text
Abstract
Novel N-halamine nanoparticles potentially useful for killing pathogenic bacteria, i.e., SiO2@PS/N-halamine NPs, were successfully synthesized via the immobilization of N-halamines onto the polystyrene-coated silica nanoparticles (SiO2@PS NPs). The effect of reaction conditions, i.e.,
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Novel N-halamine nanoparticles potentially useful for killing pathogenic bacteria, i.e., SiO2@PS/N-halamine NPs, were successfully synthesized via the immobilization of N-halamines onto the polystyrene-coated silica nanoparticles (SiO2@PS NPs). The effect of reaction conditions, i.e., chlorination temperature, bleaching concentration, chlorination time, on the oxidative chlorine content in the products was systematically investigated. The antibacterial activity of the products was tested via the modified plate counting methd using Escherichia coli (E. coli) as a model bacterium. The possible mechanism of the antibacterial action of the products was also studied using scanning electron microscopy combined with a inhibition zone study. The antimicrobial capability of the products was well controlled by tuning the oxidative chlorine content in the products. More importantly, the role of DksA protein in the susceptibility of E. coli against the products was proven using a time-kill assay. This in-depth investigation of the sensitivity of E. coli towards N-halamine NPs provides a systematic understanding of the utility of N-halamines for deactivating bacteria or even disease control. Full article
(This article belongs to the Special Issue Prodrugs)
Open AccessArticle Synthesis, Anti-Tumor and Anti-Angiogenic Activity Evaluations of Asiatic Acid Amino Acid Derivatives
Molecules 2015, 20(4), 7309-7324; doi:10.3390/molecules20047309
Received: 6 March 2015 / Revised: 15 April 2015 / Accepted: 17 April 2015 / Published: 21 April 2015
Cited by 7 | PDF Full-text (1662 KB) | HTML Full-text | XML Full-text
Abstract
Fifteen semi-synthetic derivatives of asiatic acid (AA) have been synthesized and evaluated for their biological activities. The successful modification of these compounds at the C-2, C-3, C-23 and C-28 positions was confirmed using NMR, MS and IR spectra. Further, their anti-tumor effects were
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Fifteen semi-synthetic derivatives of asiatic acid (AA) have been synthesized and evaluated for their biological activities. The successful modification of these compounds at the C-2, C-3, C-23 and C-28 positions was confirmed using NMR, MS and IR spectra. Further, their anti-tumor effects were evaluated in vitro using different cancer cell lines (HeLa, HepG2, B16F10, SGC7901, A549, MCF7 and PC3), while their anti-angiogenic activities were evaluated in vivo using a larval zebrafish model. Among the derivatives, compounds 410 showed more potent cytotoxic and anti-angiogenic effects than AA, while compounds 1117 had significantly less effects. The new derivative 10 was also included in finished formulations to evaluate its stability using HPLC due to its potential topical use. The derivative 10 had markedly better anti-tumor activities than both AA and other derivatives, with similar stability as its parent compound AA. Full article
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Open AccessArticle Investigation of a Quantitative Method for the Analysis of Chiral Monoterpenes in White Wine by HS-SPME-MDGC-MS of Different Wine Matrices
Molecules 2015, 20(4), 7359-7378; doi:10.3390/molecules20047359
Received: 16 March 2015 / Revised: 16 April 2015 / Accepted: 16 April 2015 / Published: 22 April 2015
Cited by 4 | PDF Full-text (829 KB) | HTML Full-text | XML Full-text
Abstract
A valid quantitative method for the analysis of chiral monoterpenes in white wine using head-space solid phase micro-extraction-MDGC-MS (HS-SPME-MDGC-MS) with stable isotope dilution analysis was established. Fifteen compounds: (S)-(−)-limonene, (R)-(+)-limonene, (+)-(2R,4S)-cis-rose oxide, (−)-(2S,4R)-cis-rose oxide, (−)-(2R,4R)-trans-rose oxide, (+)-(2S,4S)-
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A valid quantitative method for the analysis of chiral monoterpenes in white wine using head-space solid phase micro-extraction-MDGC-MS (HS-SPME-MDGC-MS) with stable isotope dilution analysis was established. Fifteen compounds: (S)-(−)-limonene, (R)-(+)-limonene, (+)-(2R,4S)-cis-rose oxide, (−)-(2S,4R)-cis-rose oxide, (−)-(2R,4R)-trans-rose oxide, (+)-(2S,4S)-cis-rose oxide, furanoid (+)-trans-linalool oxide, furanoid (−)-cis-linalool oxide, furanoid (−)-trans-linalool oxide, furanoid (+)-cis-linalool oxide, (−)-linalool, (+)-linalool, (−)-α-terpineol, (+)-α-terpineol and (R)-(+)-β-citronellol were quantified. Two calibration curves were plotted for different wine bases, with varying residual sugar content, and three calibration curves for each wine base were investigated during a single fiber’s lifetime. This was needed as both sugar content and fiber life impacted the quantification of the chiral terpenes. The chiral monoterpene content of six Pinot Gris wines and six Riesling wines was then analyzed using the verified method. ANOVA with Tukey multiple comparisons showed significant differences for each of the detected chiral compounds in all 12 wines. PCA score plots showed a clear separation between the Riesling and Pinot Gris wines. Riesling wines had greater number of chiral terpenes in comparison to Pinot Gris wines. Beyond total terpene content it is possible that the differences in chiral terpene content may be driving the aromatic differences in white wines. Full article
(This article belongs to the collection Wine Chemistry)
Open AccessArticle Copper(I) Complexes of Mesoionic Carbene: Structural Characterization and Catalytic Hydrosilylation Reactions
Molecules 2015, 20(4), 7379-7395; doi:10.3390/molecules20047379
Received: 24 February 2015 / Revised: 20 March 2015 / Accepted: 23 March 2015 / Published: 22 April 2015
Cited by 8 | PDF Full-text (926 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Two series of different Cu(I)-complexes of “click” derived mesoionic carbenes are reported. Halide complexes of the type (MIC)CuI (with MIC = 1,4-(2,6-diisopropyl)-phenyl-3-methyl-1,2,3-triazol-5-ylidene (for 1b), 1-benzyl-3-methyl-4-phenyl-1,2,3-triazol-5-ylidene (for 1c)) and cationic complexes of the general formula [Cu(MIC)2]X (with MIC =1,4-dimesityl-3-methyl-1,2,3-triazol-5-ylidene, X
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Two series of different Cu(I)-complexes of “click” derived mesoionic carbenes are reported. Halide complexes of the type (MIC)CuI (with MIC = 1,4-(2,6-diisopropyl)-phenyl-3-methyl-1,2,3-triazol-5-ylidene (for 1b), 1-benzyl-3-methyl-4-phenyl-1,2,3-triazol-5-ylidene (for 1c)) and cationic complexes of the general formula [Cu(MIC)2]X (with MIC =1,4-dimesityl-3-methyl-1,2,3-triazol-5-ylidene, X = CuI2 (for ), 1,4-dimesityl-3-methyl-1,2,3-triazol-5-ylidene, X = BF4 (for 2a), 1,4-(2,6-diisopropyl)phenyl-3-methyl-1,2,3-triazol-5-ylidene, X = BF4 (for 2b), 1-benzyl-3-methyl-4-phenyl-1,2,3-triazol-5-ylidene, X = BF4 (for 2c)) have been prepared from CuI or [Cu(CH3CN)4](BF4) and the corresponding ligands, respectively. All complexes were characterized by elemental analysis and standard spectroscopic methods. Complexes 2á and 1b were studied by single-crystal X-ray diffraction analysis. Structural analysis revealed 2á to adopt a cationic form as [Cu(MIC)2](CuI2) and comparison of the NMR spectra of 2á and 2a confirmed this conformation in solution. In contrast, after crystallization complex 1b was found to adopt the desired neutral form. All complexes were tested for the reduction of cyclohexanone under hydrosilylation condition at elevated temperatures. These complexes were found to be efficient catalysts for this reaction. 2c was also found to catalyze this reaction at room temperature. Mechanistic studies have been carried out as well. Full article
(This article belongs to the Special Issue Advances in Click Chemistry)
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Open AccessReview Antibiotic Discovery: Combatting Bacterial Resistance in Cells and in Biofilm Communities
Molecules 2015, 20(4), 5286-5298; doi:10.3390/molecules20045286
Received: 12 February 2015 / Revised: 11 March 2015 / Accepted: 18 March 2015 / Published: 24 March 2015
Cited by 52 | PDF Full-text (1301 KB) | HTML Full-text | XML Full-text
Abstract
Bacterial resistance is a rapidly escalating threat to public health as our arsenal of effective antibiotics dwindles. Therefore, there is an urgent need for new antibiotics. Drug discovery has historically focused on bacteria growing in planktonic cultures. Many antibiotics were originally developed to
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Bacterial resistance is a rapidly escalating threat to public health as our arsenal of effective antibiotics dwindles. Therefore, there is an urgent need for new antibiotics. Drug discovery has historically focused on bacteria growing in planktonic cultures. Many antibiotics were originally developed to target individual bacterial cells, being assessed in vitro against microorganisms in a planktonic mode of life. However, towards the end of the 20th century it became clear that many bacteria live as complex communities called biofilms in their natural habitat, and this includes habitats within a human host. The biofilm mode of life provides advantages to microorganisms, such as enhanced resistance towards environmental stresses, including antibiotic challenge. The community level resistance provided by biofilms is distinct from resistance mechanisms that operate at a cellular level, and cannot be overlooked in the development of novel strategies to combat infectious diseases. The review compares mechanisms of antibiotic resistance at cellular and community levels in the light of past and present antibiotic discovery efforts. Future perspectives on novel strategies for treatment of biofilm-related infectious diseases are explored. Full article
Open AccessReview Functional Thermoplastic Materials from Derivatives of Cellulose and Related Structural Polysaccharides
Molecules 2015, 20(4), 5487-5527; doi:10.3390/molecules20045487
Received: 22 November 2014 / Revised: 10 March 2015 / Accepted: 19 March 2015 / Published: 27 March 2015
Cited by 5 | PDF Full-text (7419 KB) | HTML Full-text | XML Full-text
Abstract
This review surveys advances in the development of various material functionalities based on thermoplastic cellulose and related structural polysaccharide derivatives. First, the dependence of thermal (phase) transition behavior on the molecular composition of simple derivatives is rationalized. Next, approaches enabling effective thermoplasticization and
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This review surveys advances in the development of various material functionalities based on thermoplastic cellulose and related structural polysaccharide derivatives. First, the dependence of thermal (phase) transition behavior on the molecular composition of simple derivatives is rationalized. Next, approaches enabling effective thermoplasticization and further incorporation of material functionalities into structural polysaccharides are discussed. These approaches include: (a) single-substituent derivatization, (b) derivatization with multi-substituents, (c) blending of simple derivatives with synthetic polymers, and (d) graft copolymerization. Some examples addressing the control of supramolecular structures and the regulation of molecular and segmental orientations for functional materials fabrication, which have especially progressed over the past decade, are also addressed. Attractive material functions include improved mechanical performance, controlled biodegradability, cytocompatiblity, and optical functions. Full article
(This article belongs to the Special Issue New Trends in Cellulose and Chitin Chemistry)
Open AccessReview Tetrazolium Compounds: Synthesis and Applications in Medicine
Molecules 2015, 20(4), 5528-5553; doi:10.3390/molecules20045528
Received: 9 December 2014 / Revised: 3 March 2015 / Accepted: 4 March 2015 / Published: 27 March 2015
Cited by 18 | PDF Full-text (568 KB) | HTML Full-text | XML Full-text
Abstract
Tetrazoles represent a class of five-membered heterocyclic compounds with polynitrogen electron-rich planar structural features. This special structure makes tetrazole derivatives useful drugs, explosives, and other functional materials with a wide range of applications in many fields of medicine, agriculture, material science, etc. Based
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Tetrazoles represent a class of five-membered heterocyclic compounds with polynitrogen electron-rich planar structural features. This special structure makes tetrazole derivatives useful drugs, explosives, and other functional materials with a wide range of applications in many fields of medicine, agriculture, material science, etc. Based on our research works on azoles and other references in recent years, this review covers reported work on the synthesis and biological activities of tetrazole derivatives. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessReview A Review of Heterogeneous Photocatalysis for Water and Surface Disinfection
Molecules 2015, 20(4), 5574-5615; doi:10.3390/molecules20045574
Received: 29 December 2014 / Revised: 16 March 2015 / Accepted: 18 March 2015 / Published: 30 March 2015
Cited by 38 | PDF Full-text (2981 KB) | HTML Full-text | XML Full-text
Abstract
Photo-excitation of certain semiconductors can lead to the production of reactive oxygen species that can inactivate microorganisms. The mechanisms involved are reviewed, along with two important applications. The first is the use of photocatalysis to enhance the solar disinfection of water. It is
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Photo-excitation of certain semiconductors can lead to the production of reactive oxygen species that can inactivate microorganisms. The mechanisms involved are reviewed, along with two important applications. The first is the use of photocatalysis to enhance the solar disinfection of water. It is estimated that 750 million people do not have accessed to an improved source for drinking and many more rely on sources that are not safe. If one can utilize photocatalysis to enhance the solar disinfection of water and provide an inexpensive, simple method of water disinfection, then it could help reduce the risk of waterborne disease. The second application is the use of photocatalytic coatings to combat healthcare associated infections. Two challenges are considered, i.e., the use of photocatalytic coatings to give “self-disinfecting” surfaces to reduce the risk of transmission of infection via environmental surfaces, and the use of photocatalytic coatings for the decontamination and disinfection of medical devices. In the final section, the development of novel photocatalytic materials for use in disinfection applications is reviewed, taking account of materials, developed for other photocatalytic applications, but which may be transferable for disinfection purposes. Full article
(This article belongs to the Special Issue Photocatalysis) Printed Edition available
Open AccessReview Nanoporous Materials as New Engineered Catalysts for the Synthesis of Green Fuels
Molecules 2015, 20(4), 5638-5666; doi:10.3390/molecules20045638
Received: 4 February 2015 / Revised: 18 March 2015 / Accepted: 23 March 2015 / Published: 31 March 2015
Cited by 18 | PDF Full-text (828 KB) | HTML Full-text | XML Full-text
Abstract
This review summarizes the importance of nanoporous materials and their fascinating structural properties with respect to the catalytic and photocatalytic reduction of CO2 to methane, toward achieving a sustainable energy supply. The importance of catalysis as a bridge step for advanced energy
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This review summarizes the importance of nanoporous materials and their fascinating structural properties with respect to the catalytic and photocatalytic reduction of CO2 to methane, toward achieving a sustainable energy supply. The importance of catalysis as a bridge step for advanced energy systems and the associated environmental issues are stressed. A deep understanding of the fundamentals of these nanoporous solids is necessary to improve the design and efficiency of CO2 methanation. The role of the support dominates the design in terms of developing an efficient methanation catalyst, specifically with respect to ensuring enhanced metal dispersion and a long catalyst lifetime. Nanoporous materials provide the best supports for Ni, Ru, Rh, Co, Fe particles because they can prevent sintering and deactivation through coking, which otherwise blocks the metal surface as carbon accumulates. This review concludes with the major challenges facing the CO2 methanation by nanoporous materials for fuel applications. Full article
(This article belongs to the Special Issue Zeolite Chemistry)
Open AccessReview Nitric Oxide Donors and Selective Carbonic Anhydrase Inhibitors: A Dual Pharmacological Approach for the Treatment of Glaucoma, Cancer and Osteoporosis
Molecules 2015, 20(4), 5667-5679; doi:10.3390/molecules20045667
Received: 23 February 2015 / Revised: 15 March 2015 / Accepted: 24 March 2015 / Published: 31 March 2015
Cited by 15 | PDF Full-text (658 KB) | HTML Full-text | XML Full-text
Abstract
Due to the recognized biological role of nitric oxide (NO) donating derivatives and of selective inhibitors of specific human carbonic anhydrase isoforms (CA, EC 4.2.1.1), promising compounds having an aromatic/heterocyclic primary sulfonamide and functionalized with NO-releasing moieties have been designed. These bifunctional agents
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Due to the recognized biological role of nitric oxide (NO) donating derivatives and of selective inhibitors of specific human carbonic anhydrase isoforms (CA, EC 4.2.1.1), promising compounds having an aromatic/heterocyclic primary sulfonamide and functionalized with NO-releasing moieties have been designed. These bifunctional agents have been tested in vitro and in vivo to assess their dual pharmacological activity. According to the encouraging results they could be proposed for the treatment of angle-open glaucoma, cancer regression and osteoporosis, in which both NO and CA activities are involved. Full article
(This article belongs to the Special Issue Nitric Oxide (NO) Release Chemistry)
Open AccessReview The Encapsulation of Anthocyanins from Berry-Type Fruits. Trends in Foods
Molecules 2015, 20(4), 5875-5888; doi:10.3390/molecules20045875
Received: 15 December 2014 / Revised: 6 March 2015 / Accepted: 9 March 2015 / Published: 3 April 2015
Cited by 7 | PDF Full-text (907 KB) | HTML Full-text | XML Full-text
Abstract
During the last decade, many berry-type fruits have been recognised as good sources of anthocyanins. Nevertheless, the use of anthocyanins in the development of food colourants and healthy and/or functional ingredients has been limited because of their low stability under given environmental conditions
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During the last decade, many berry-type fruits have been recognised as good sources of anthocyanins. Nevertheless, the use of anthocyanins in the development of food colourants and healthy and/or functional ingredients has been limited because of their low stability under given environmental conditions and interaction with other compounds in the food matrix. This review compiles information about the encapsulation of anthocyanins from twelve different berry-type fruit species as a technology for improving the stability and/or bioavailability of anthocyanins. Encapsulation by spray drying has been the primary method used to encapsulate anthocyanins, and some studies attempt to keep anthocyanin microparticles stable during storage. Nevertheless, more studies are needed to determine the stability of anthocyanin microparticles in food matrices over the product shelf life in the development of food colourants. Studies about encapsulated anthocyanins in simulated gastrointestinal models have primarily been conducted on the release of anthocyanins from microparticles to evaluate their bioavailability. However, adding anthocyanin microparticles to a food vehicle must guarantee the health properties attributed to the specific anthocyanins present in berry-type fruits. Full article
(This article belongs to the Special Issue Anthocyanins) Printed Edition available
Open AccessReview Appropriate First-Line Regimens to Combat Helicobacter pylori Antibiotic Resistance: An Asian Perspective
Molecules 2015, 20(4), 6068-6092; doi:10.3390/molecules20046068
Received: 25 February 2015 / Revised: 20 March 2015 / Accepted: 2 April 2015 / Published: 8 April 2015
Cited by 12 | PDF Full-text (775 KB) | HTML Full-text | XML Full-text
Abstract
Asia has the largest population of any continent and the highest incidence of gastric cancer in the world, making it very important in the context of Helicobacter pylori infection. According to current guidelines, standard triple therapy containing a proton pump inhibitor (PPI) and
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Asia has the largest population of any continent and the highest incidence of gastric cancer in the world, making it very important in the context of Helicobacter pylori infection. According to current guidelines, standard triple therapy containing a proton pump inhibitor (PPI) and two antibiotics; amoxicillin (AMX) and clarithromycin (CAM) or metronidazole (MNZ), is still the preferred first-line regimen for treatment of H. pylori infection. However, the efficacy of legacy triple regimens has been seriously challenged, and they are gradually becoming ineffective. Moreover, some regions in Asia show patterns of emerging antimicrobial resistance. More effective regimens including the bismuth and non-bismuth quadruple, sequential, and dual-concomitant (hybrid) regimens are now replacing standard triple therapies as empirical first-line treatments on the basis of the understanding of the local prevalence of H. pylori antimicrobial resistance. Selection of PPI metabolized by the non-enzymatic pathway or minimal first pass metabolism and/or increasing dose of PPI are important to increase H. pylori eradication rates. Therefore, local antibiotic resistance surveillance updates, selection of appropriate first-line regimens with non-enzymatic PPI and/or increased doses of PPI, and detailed evaluation of patients’ prior antibiotic usage are all essential information to combat H. pylori antibiotic resistance in Asia. Full article
Open AccessReview Thapsigargin—From Thapsia L. to Mipsagargin
Molecules 2015, 20(4), 6113-6127; doi:10.3390/molecules20046113
Received: 25 February 2015 / Revised: 26 March 2015 / Accepted: 30 March 2015 / Published: 8 April 2015
Cited by 16 | PDF Full-text (1541 KB) | HTML Full-text | XML Full-text
Abstract
The sesquiterpene lactone thapsigargin is found in the plant Thapsia garganica L., and is one of the major constituents of the roots and fruits of this Mediterranean species. In 1978, the first pharmacological effects of thapsigargin were established and the full structure was
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The sesquiterpene lactone thapsigargin is found in the plant Thapsia garganica L., and is one of the major constituents of the roots and fruits of this Mediterranean species. In 1978, the first pharmacological effects of thapsigargin were established and the full structure was elucidated in 1985. Shortly after, the overall mechanism of the Sarco-endoplasmic reticulum Ca2+-ATPase (SERCA) inhibition that leads to apoptosis was discovered. Thapsigargin has a potent antagonistic effect on the SERCA and is widely used to study Ca2+-signaling. The effect on SERCA has also been utilized in the treatment of solid tumors. A prodrug has been designed to target the blood vessels of cancer cells; the death of these blood vessels then leads to tumor necrosis. The first clinical trials of this drug were initiated in 2008, and the potent drug is expected to enter the market in the near future under the generic name Mipsagargin (G-202). This review will describe the discovery of the new drug, the on-going elucidation of the biosynthesis of thapsigargin in the plant and attempts to supply the global market with a novel potent anti-cancer drug. Full article
Open AccessReview Model Organisms in the Fight against Muscular Dystrophy: Lessons from Drosophila and Zebrafish
Molecules 2015, 20(4), 6237-6253; doi:10.3390/molecules20046237
Received: 24 February 2015 / Revised: 31 March 2015 / Accepted: 1 April 2015 / Published: 9 April 2015
Cited by 10 | PDF Full-text (765 KB) | HTML Full-text | XML Full-text
Abstract
Muscular dystrophies (MD) are a heterogeneous group of genetic disorders that cause muscle weakness, abnormal contractions and muscle wasting, often leading to premature death. More than 30 types of MD have been described so far; those most thoroughly studied are Duchenne muscular dystrophy
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Muscular dystrophies (MD) are a heterogeneous group of genetic disorders that cause muscle weakness, abnormal contractions and muscle wasting, often leading to premature death. More than 30 types of MD have been described so far; those most thoroughly studied are Duchenne muscular dystrophy (DMD), myotonic dystrophy type 1 (DM1) and congenital MDs. Structurally, physiologically and biochemically, MDs affect different types of muscles and cause individual symptoms such that genetic and molecular pathways underlying their pathogenesis thus remain poorly understood. To improve our knowledge of how MD-caused muscle defects arise and to find efficacious therapeutic treatments, different animal models have been generated and applied. Among these, simple non-mammalian Drosophila and zebrafish models have proved most useful. This review discusses how zebrafish and Drosophila MD have helped to identify genetic determinants of MDs and design innovative therapeutic strategies with a special focus on DMD, DM1 and congenital MDs. Full article
Open AccessReview Insights into the Antimicrobial Properties of Hepcidins: Advantages and Drawbacks as Potential Therapeutic Agents
Molecules 2015, 20(4), 6319-6341; doi:10.3390/molecules20046319
Received: 6 March 2015 / Revised: 30 March 2015 / Accepted: 3 April 2015 / Published: 10 April 2015
Cited by 11 | PDF Full-text (1680 KB) | HTML Full-text | XML Full-text
Abstract
The increasing frequency of multi-drug resistant microorganisms has driven research into alternative therapeutic strategies. In this respect, natural antimicrobial peptides (AMPs) hold much promise as candidates for the development of novel antibiotics. However, AMPs have some intrinsic drawbacks, such as partial degradation by
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The increasing frequency of multi-drug resistant microorganisms has driven research into alternative therapeutic strategies. In this respect, natural antimicrobial peptides (AMPs) hold much promise as candidates for the development of novel antibiotics. However, AMPs have some intrinsic drawbacks, such as partial degradation by host proteases or inhibition by host body fluid composition, potential toxicity, and high production costs. This review focuses on the hepcidins, which are peptides produced by the human liver with a known role in iron homeostasis, as well by numerous other organisms (including fish, reptiles, other mammals), and their potential as antibacterial and antifungal agents. Interestingly, the antimicrobial properties of human hepcidins are enhanced at acidic pH, rendering these peptides appealing for the design of new drugs targeting infections that occur in body areas with acidic physiological pH. This review not only considers current research on the direct killing activity of these peptides, but evaluates the potential application of these molecules as coating agents preventing biofilm formation and critically assesses technical obstacles preventing their therapeutic application. Full article
Open AccessReview Heparin/Heparan Sulfate Proteoglycans Glycomic Interactome in Angiogenesis: Biological Implications and Therapeutical Use
Molecules 2015, 20(4), 6342-6388; doi:10.3390/molecules20046342
Received: 26 February 2015 / Revised: 31 March 2015 / Accepted: 1 April 2015 / Published: 10 April 2015
Cited by 27 | PDF Full-text (1610 KB) | HTML Full-text | XML Full-text
Abstract
Angiogenesis, the process of formation of new blood vessel from pre-existing ones, is involved in various intertwined pathological processes including virus infection, inflammation and oncogenesis, making it a promising target for the development of novel strategies for various interventions. To induce angiogenesis, angiogenic
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Angiogenesis, the process of formation of new blood vessel from pre-existing ones, is involved in various intertwined pathological processes including virus infection, inflammation and oncogenesis, making it a promising target for the development of novel strategies for various interventions. To induce angiogenesis, angiogenic growth factors (AGFs) must interact with pro-angiogenic receptors to induce proliferation, protease production and migration of endothelial cells (ECs). The action of AGFs is counteracted by antiangiogenic modulators whose main mechanism of action is to bind (thus sequestering or masking) AGFs or their receptors. Many sugars, either free or associated to proteins, are involved in these interactions, thus exerting a tight regulation of the neovascularization process. Heparin and heparan sulfate proteoglycans undoubtedly play a pivotal role in this context since they bind to almost all the known AGFs, to several pro-angiogenic receptors and even to angiogenic inhibitors, originating an intricate network of interaction, the so called “angiogenesis glycomic interactome”. The decoding of the angiogenesis glycomic interactome, achievable by a systematic study of the interactions occurring among angiogenic modulators and sugars, may help to design novel antiangiogenic therapies with implications in the cure of angiogenesis-dependent diseases. Full article
(This article belongs to the Special Issue Protein-Carbohydrate Interactions, and Beyond)
Open AccessReview Exploiting Protected Maleimides to Modify Oligonucleotides, Peptides and Peptide Nucleic Acids
Molecules 2015, 20(4), 6389-6408; doi:10.3390/molecules20046389
Received: 12 February 2015 / Revised: 27 March 2015 / Accepted: 31 March 2015 / Published: 10 April 2015
Cited by 9 | PDF Full-text (382 KB) | HTML Full-text | XML Full-text
Abstract
This manuscript reviews the possibilities offered by 2,5-dimethylfuran-protected maleimides. Suitably derivatized building blocks incorporating the exo Diels-Alder cycloadduct can be introduced at any position of oligonucleotides, peptide nucleic acids, peptides and peptoids, making use of standard solid-phase procedures. Maleimide deprotection takes place upon
[...] Read more.
This manuscript reviews the possibilities offered by 2,5-dimethylfuran-protected maleimides. Suitably derivatized building blocks incorporating the exo Diels-Alder cycloadduct can be introduced at any position of oligonucleotides, peptide nucleic acids, peptides and peptoids, making use of standard solid-phase procedures. Maleimide deprotection takes place upon heating, which can be followed by either Michael-type or Diels-Alder click conjugation reactions. However, the one-pot procedure in which maleimide deprotection and conjugation are simultaneously carried out provides the target conjugate more quickly and, more importantly, in better yield. This procedure is compatible with conjugates involving oligonucleotides, peptides and peptide nucleic acids. A variety of cyclic peptides and oligonucleotides can be obtained from peptide and oligonucleotide precursors incorporating protected maleimides and thiols. Full article
(This article belongs to the Special Issue Bioconjugations)
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Open AccessReview Longevity Extension by Phytochemicals
Molecules 2015, 20(4), 6544-6572; doi:10.3390/molecules20046544
Received: 2 March 2015 / Revised: 7 April 2015 / Accepted: 8 April 2015 / Published: 13 April 2015
Cited by 18 | PDF Full-text (741 KB) | HTML Full-text | XML Full-text
Abstract
Phytochemicals are structurally diverse secondary metabolites synthesized by plants and also by non-pathogenic endophytic microorganisms living within plants. Phytochemicals help plants to survive environmental stresses, protect plants from microbial infections and environmental pollutants, provide them with a defense from herbivorous organisms and attract
[...] Read more.
Phytochemicals are structurally diverse secondary metabolites synthesized by plants and also by non-pathogenic endophytic microorganisms living within plants. Phytochemicals help plants to survive environmental stresses, protect plants from microbial infections and environmental pollutants, provide them with a defense from herbivorous organisms and attract natural predators of such organisms, as well as lure pollinators and other symbiotes of these plants. In addition, many phytochemicals can extend longevity in heterotrophic organisms across phyla via evolutionarily conserved mechanisms. In this review, we discuss such mechanisms. We outline how structurally diverse phytochemicals modulate a complex network of signaling pathways that orchestrate a distinct set of longevity-defining cellular processes. This review also reflects on how the release of phytochemicals by plants into a natural ecosystem may create selective forces that drive the evolution of longevity regulation mechanisms in heterotrophic organisms inhabiting this ecosystem. We outline the most important unanswered questions and directions for future research in this vibrant and rapidly evolving field. Full article
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Open AccessReview Studies on the Alkaloids of the Calycanthaceae and Their Syntheses
Molecules 2015, 20(4), 6715-6738; doi:10.3390/molecules20046715
Received: 14 February 2015 / Revised: 18 March 2015 / Accepted: 3 April 2015 / Published: 15 April 2015
Cited by 7 | PDF Full-text (1388 KB) | HTML Full-text | XML Full-text
Abstract
Plants of the Calycanthaceae family, which possesses four genera and about 15 species, are mainly distributed in China, North America and Australia. Chemical studies on the Calycanthaceae have led to the discovery of about 14 alkaloids of different skeletons, including dimeric piperidinoquinoline, dimeric
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Plants of the Calycanthaceae family, which possesses four genera and about 15 species, are mainly distributed in China, North America and Australia. Chemical studies on the Calycanthaceae have led to the discovery of about 14 alkaloids of different skeletons, including dimeric piperidinoquinoline, dimeric pyrrolidinoindoline and/or trimeric pyrrolidinoindolines, which exhibit significant anti-convulsant, anti-fungal, anti-viral analgesic, anti-tumor, and anti-melanogenesis activities. As some of complex tryptamine-derived alkaloids exhibit promising biological activities, the syntheses of these alkaloids have also been a topic of interest in synthetic chemistry during the last decades. This review will focus on the structures and total syntheses of these alkaloids. Full article
(This article belongs to the collection Bioactive Compounds)
Open AccessReview Advances and Recent Trends in Heterogeneous Photo(Electro)-Catalysis for Solar Fuels and Chemicals
Molecules 2015, 20(4), 6739-6793; doi:10.3390/molecules20046739
Received: 20 January 2015 / Revised: 20 March 2015 / Accepted: 20 March 2015 / Published: 15 April 2015
Cited by 18 | PDF Full-text (5870 KB) | HTML Full-text | XML Full-text
Abstract
In the context of a future renewable energy system based on hydrogen storage as energy-dense liquid alcohols co-synthesized from recycled CO2, this article reviews advances in photocatalysis and photoelectrocatalysis that exploit solar (photonic) primary energy in relevant endergonic processes, viz., H
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In the context of a future renewable energy system based on hydrogen storage as energy-dense liquid alcohols co-synthesized from recycled CO2, this article reviews advances in photocatalysis and photoelectrocatalysis that exploit solar (photonic) primary energy in relevant endergonic processes, viz., H2 generation by water splitting, bio-oxygenate photoreforming, and artificial photosynthesis (CO2 reduction). Attainment of the efficiency (>10%) mandated for viable techno-economics (USD 2.00–4.00 per kg H2) and implementation on a global scale hinges on the development of photo(electro)catalysts and co-catalysts composed of earth-abundant elements offering visible-light-driven charge separation and surface redox chemistry in high quantum yield, while retaining the chemical and photo-stability typical of titanium dioxide, a ubiquitous oxide semiconductor and performance “benchmark”. The dye-sensitized TiO2 solar cell and multi-junction Si are key “voltage-biasing” components in hybrid photovoltaic/photoelectrochemical (PV/PEC) devices that currently lead the field in performance. Prospects and limitations of visible-absorbing particulates, e.g., nanotextured crystalline α-Fe2O3, g-C3N4, and TiO2 sensitized by C/N-based dopants, multilayer composites, and plasmonic metals, are also considered. An interesting trend in water splitting is towards hydrogen peroxide as a solar fuel and value-added green reagent. Fundamental and technical hurdles impeding the advance towards pre-commercial solar fuels demonstration units are considered. Full article
(This article belongs to the Special Issue Photocatalysis) Printed Edition available
Open AccessReview Predicting the Uncertain Future of Aptamer-Based Diagnostics and Therapeutics
Molecules 2015, 20(4), 6866-6887; doi:10.3390/molecules20046866
Received: 19 March 2015 / Revised: 4 April 2015 / Accepted: 7 April 2015 / Published: 16 April 2015
Cited by 34 | PDF Full-text (1435 KB) | HTML Full-text | XML Full-text
Abstract
Despite the great promise of nucleic acid aptamers in the areas of diagnostics and therapeutics for their facile in vitro development, lack of immunogenicity and other desirable properties, few truly successful aptamer-based products exist in the clinical or other markets. Core reasons for
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Despite the great promise of nucleic acid aptamers in the areas of diagnostics and therapeutics for their facile in vitro development, lack of immunogenicity and other desirable properties, few truly successful aptamer-based products exist in the clinical or other markets. Core reasons for these commercial deficiencies probably stem from industrial commitment to antibodies including a huge financial investment in humanized monoclonal antibodies and a general ignorance about aptamers and their performance among the research and development community. Given the early failures of some strong commercial efforts to gain government approval and bring aptamer-based products to market, it may seem that aptamers are doomed to take a backseat to antibodies forever. However, the key advantages of aptamers over antibodies coupled with niche market needs that only aptamers can fill and more recent published data still point to a bright commercial future for aptamers in areas such as infectious disease and cancer diagnostics and therapeutics. As more researchers and entrepreneurs become familiar with aptamers, it seems inevitable that aptamers will at least be considered for expanded roles in diagnostics and therapeutics. This review also examines new aptamer modifications and attempts to predict new aptamer applications that could revolutionize biomedical technology in the future and lead to marketed products. Full article
(This article belongs to the Special Issue Aptamers: Past, Present, and Future)
Open AccessReview Kinugasa Reactions in Water: From Green Chemistry to Bioorthogonal Labelling
Molecules 2015, 20(4), 6959-6969; doi:10.3390/molecules20046959
Received: 30 March 2015 / Revised: 12 April 2015 / Accepted: 13 April 2015 / Published: 16 April 2015
Cited by 12 | PDF Full-text (593 KB) | HTML Full-text | XML Full-text | Correction
Abstract
The Kinugasa reaction has become an efficient method for the direct synthesis of β-lactams from substituted nitrones and copper(I) acetylides. In recent years, the reaction scope has been expanded to include the use of water as the solvent, and with micelle-promoted [3+2] cycloadditions
[...] Read more.
The Kinugasa reaction has become an efficient method for the direct synthesis of β-lactams from substituted nitrones and copper(I) acetylides. In recent years, the reaction scope has been expanded to include the use of water as the solvent, and with micelle-promoted [3+2] cycloadditions followed by rearrangement furnishing high yields of β-lactams. The high yields of stable products under aqueous conditions render the modified Kinugasa reaction amenable to metabolic labelling and bioorthogonal applications. Herein, the development of methods for use of the Kinugasa reaction in aqueous media is reviewed, with emphasis on its potential use as a bioorthogonal coupling strategy. Full article
(This article belongs to the Special Issue Recent Developments of the Kinugasa Reaction)
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Open AccessReview Perinatal Asphyxia: A Review from a Metabolomics Perspective
Molecules 2015, 20(4), 7000-7016; doi:10.3390/molecules20047000
Received: 19 February 2015 / Revised: 1 April 2015 / Accepted: 13 April 2015 / Published: 17 April 2015
Cited by 11 | PDF Full-text (690 KB) | HTML Full-text | XML Full-text
Abstract
Perinatal asphyxia is defined as an oxygen deprivation that occurs around the time of birth, and may be caused by several perinatal events. This medical condition affects some four million neonates worldwide per year, causing the death of one million subjects. In most
[...] Read more.
Perinatal asphyxia is defined as an oxygen deprivation that occurs around the time of birth, and may be caused by several perinatal events. This medical condition affects some four million neonates worldwide per year, causing the death of one million subjects. In most cases, infants successfully recover from hypoxia episodes; however, some patients may develop HIE, leading to permanent neurological conditions or impairment of different organs and systems. Given its multifactor dependency, the timing, severity and outcome of this disease, mainly assessed through Sarnat staging, are of difficult evaluation. Moreover, although the latest newborn resuscitation guideline suggests the use of a 21% oxygen concentration or room air, such an approach is still under debate. Therefore, the pathological mechanism is still not clear and a golden standard treatment has yet to be defined. In this context, metabolomics, a new discipline that has described important perinatal issues over the last years, proved to be a useful tool for the monitoring, the assessment, and the identification of potential biomarkers associated with asphyxia events. This review covers metabolomics research on perinatal asphyxia condition, examining in detail the studies reported both on animal and human models. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessReview A Survey of Marine Natural Compounds and Their Derivatives with Anti-Cancer Activity Reported in 2012
Molecules 2015, 20(4), 7097-7142; doi:10.3390/molecules20047097
Received: 21 January 2015 / Revised: 1 April 2015 / Accepted: 3 April 2015 / Published: 20 April 2015
Cited by 17 | PDF Full-text (1111 KB) | HTML Full-text | XML Full-text
Abstract
Although considerable effort and progress has been made in the search for new anticancer drugs and treatments in the last several decades, cancer remains a major public health problem and one of the major causes of death worldwide. Many sources, including plants, animals,
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Although considerable effort and progress has been made in the search for new anticancer drugs and treatments in the last several decades, cancer remains a major public health problem and one of the major causes of death worldwide. Many sources, including plants, animals, and minerals, are of interest in cancer research because of the possibility of identifying novel molecular therapeutics. Moreover, structure-activity-relationship (SAR) investigations have become a common way to develop naturally derived or semi-synthetic molecular analogues with improved efficacy and decreased toxicity. In 2012, approximately 138 molecules from marine sources, including isolated compounds and their associated analogues, were shown to be promising anticancer drugs. Among these, 62% are novel compounds. In this report, we review the marine compounds identified in 2012 that may serve as novel anticancer drugs. Full article
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Open AccessReview Recent Developments of Versatile Photoinitiating Systems for Cationic Ring Opening Polymerization Operating at Any Wavelengths and under Low Light Intensity Sources
Molecules 2015, 20(4), 7201-7221; doi:10.3390/molecules20047201
Received: 25 February 2015 / Revised: 27 March 2015 / Accepted: 30 March 2015 / Published: 20 April 2015
Cited by 16 | PDF Full-text (2276 KB) | HTML Full-text | XML Full-text
Abstract
Photoinitiators (PI) or photoinitiating systems (PIS) usable in light induced cationic polymerization (CP) and free radical promoted cationic polymerization (FRPCP) reactions (more specifically for cationic ring opening polymerization (ROP)) together with the involved mechanisms are briefly reviewed. The recent developments of novel two-
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Photoinitiators (PI) or photoinitiating systems (PIS) usable in light induced cationic polymerization (CP) and free radical promoted cationic polymerization (FRPCP) reactions (more specifically for cationic ring opening polymerization (ROP)) together with the involved mechanisms are briefly reviewed. The recent developments of novel two- and three-component PISs for CP and FRPCP upon exposure to low intensity blue to red lights is emphasized in details. Examples of such reactions under various experimental conditions are provided. Full article
(This article belongs to the Special Issue Ring-Opening Polymerization)
Open AccessReview Antibacterial Activity of Essential Oils and Their Isolated Constituents against Cariogenic Bacteria: A Systematic Review
Molecules 2015, 20(4), 7329-7358; doi:10.3390/molecules20047329
Received: 24 February 2015 / Revised: 4 April 2015 / Accepted: 10 April 2015 / Published: 22 April 2015
Cited by 32 | PDF Full-text (1033 KB) | HTML Full-text | XML Full-text
Abstract
Dental caries remains the most prevalent and costly oral infectious disease worldwide. Several methods have been employed to prevent this biofilm-dependent disease, including the use of essential oils (EOs). In this systematic review, we discuss the antibacterial activity of EOs and their isolated
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Dental caries remains the most prevalent and costly oral infectious disease worldwide. Several methods have been employed to prevent this biofilm-dependent disease, including the use of essential oils (EOs). In this systematic review, we discuss the antibacterial activity of EOs and their isolated constituents in view of a potential applicability in novel dental formulations. Seven databases were systematically searched for clinical trials, in situ, in vivo and in vitro studies addressing the topic published up to date. Most of the knowledge in the literature is based on in vitro studies assessing the effects of EOs on caries-related streptococci (mainly Streptococcus mutans) and lactobacilli, and on a limited number of clinical trials. The most promising species with antibacterial potential against cariogenic bacteria are: Achillea ligustica, Baccharis dracunculifolia, Croton cajucara, Cryptomeria japonica, Coriandrum sativum, Eugenia caryophyllata, Lippia sidoides, Ocimum americanum, and Rosmarinus officinalis. In some cases, the major phytochemical compounds determine the biological properties of EOs. Menthol and eugenol were considered outstanding compounds demonstrating an antibacterial potential. Only L. sidoides mouthwash (1%) has shown clinical antimicrobial effects against oral pathogens thus far. This review suggests avenues for further non-clinical and clinical studies with the most promising EOs and their isolated constituents bioprospected worldwide. Full article
(This article belongs to the Section Metabolites)
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Open AccessReview Phytomelatonin: Assisting Plants to Survive and Thrive
Molecules 2015, 20(4), 7396-7437; doi:10.3390/molecules20047396
Received: 25 February 2015 / Revised: 27 March 2015 / Accepted: 27 March 2015 / Published: 22 April 2015
Cited by 71 | PDF Full-text (2355 KB) | HTML Full-text | XML Full-text
Abstract
This review summarizes the advances that have been made in terms of the identified functions of melatonin in plants. Melatonin is an endogenously-produced molecule in all plant species that have been investigated. Its concentration in plant organs varies in different tissues, e.g., roots
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This review summarizes the advances that have been made in terms of the identified functions of melatonin in plants. Melatonin is an endogenously-produced molecule in all plant species that have been investigated. Its concentration in plant organs varies in different tissues, e.g., roots versus leaves, and with their developmental stage. As in animals, the pathway of melatonin synthesis in plants utilizes tryptophan as an essential precursor molecule. Melatonin synthesis is inducible in plants when they are exposed to abiotic stresses (extremes of temperature, toxins, increased soil salinity, drought, etc.) as well as to biotic stresses (fungal infection). Melatonin aids plants in terms of root growth, leaf morphology, chlorophyll preservation and fruit development. There is also evidence that exogenously-applied melatonin improves seed germination, plant growth and crop yield and its application to plant products post-harvest shows that melatonin advances fruit ripening and may improve food quality. Since melatonin was only discovered in plants two decades ago, there is still a great deal to learn about the functional significance of melatonin in plants. It is the hope of the authors that the current review will serve as a stimulus for scientists to join the endeavor of clarifying the function of this phylogenetically-ancient molecule in plants and particularly in reference to the mechanisms by which melatonin mediates its multiple actions. Full article

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Open AccessCorrection Correction: Huang, W.-H., et al. Anticancer Activities of Polyynes from the Root Bark of Oplopanax horridus and Their Acetylated Derivatives. Molecules 2014, 19, 6142-6162
Molecules 2015, 20(4), 5438-5439; doi:10.3390/molecules20045438
Received: 30 January 2015 / Accepted: 26 March 2015 / Published: 26 March 2015
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Abstract
We wish to make the following changes to the published article [1], agreed upon by all authors: [...] Full article
(This article belongs to the Section Natural Products)
Open AccessCorrection Correction: Yang, C.-H., et al. Immobilization of Brassica oleracea Chlorophyllase 1 (BoCLH1) and Candida rugosa Lipase (CRL) in Magnetic Alginate Beads: An Enzymatic Evaluation in the Corresponding Proteins. Molecules 2014, 19, 11800-11815
Molecules 2015, 20(4), 7325-7328; doi:10.3390/molecules20047325
Received: 2 April 2015 / Accepted: 2 April 2015 / Published: 21 April 2015
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Abstract
The authors wish to correct Scheme 1, and Figures 1, 4 and 7 in [1] as follows. Scheme 1 should include phytol and fatty acid. [...] Full article
(This article belongs to the Special Issue Bio and Nanomaterials Based on Fe3O4)

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