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Molecules, Volume 20, Issue 6 (June 2015), Pages 9487-11631

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Open AccessArticle A Comparison of In-House Real-Time LAMP Assays with a Commercial Assay for the Detection of Pathogenic Bacteria
Molecules 2015, 20(6), 9487-9495; doi:10.3390/molecules20069487
Received: 12 April 2015 / Accepted: 20 May 2015 / Published: 25 May 2015
Cited by 4 | PDF Full-text (658 KB) | HTML Full-text | XML Full-text
Abstract
Molecular detection of bacterial pathogens based on LAMP methods is a faster and simpler approach than conventional culture methods. Although different LAMP-based methods for pathogenic bacterial detection are available, a systematic comparison of these different LAMP assays has not been performed. In this
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Molecular detection of bacterial pathogens based on LAMP methods is a faster and simpler approach than conventional culture methods. Although different LAMP-based methods for pathogenic bacterial detection are available, a systematic comparison of these different LAMP assays has not been performed. In this paper, we compared 12 in-house real-time LAMP assays with a commercialized kit (Isothermal Master Mix) for the detection of Listeria monocytogenes, Salmonella spp, Staphylococcus aureus, Escherichia coli O157, E. coli O26, E. coli O45, E. coli O103, E. coli O111, E. coli O121, E. coli O145 and Streptococcus agalactiae. False-positive results were observed in all 12 in-house real-time LAMP assays, while all the negative controls of Isothermal Master Mix remained negative after amplification. The detection limit of Isothermal Master Mix for Listeria monocytogenes, Salmonella spp, Staphylococcus aureus, Escherichia coli O157, E. coli O26, E. coli O45, E. coli O103, E. coli O111, E. coli O121 and Streptococcus agalactiae was 1 pg, whereas the sensitivity of the commercialized kit for E. coli O145 was 100 pg. In conclusion, the 12 in-house real-time LAMP assays were impractical to use, while the commercialized kit Isothermal Master Mix was useful for the detection of most bacterial pathogens. Full article
(This article belongs to the Section Molecular Diversity)
Open AccessArticle Enhanced Supersaturation and Oral Absorption of Sirolimus Using an Amorphous Solid Dispersion Based on Eudragit® E
Molecules 2015, 20(6), 9496-9509; doi:10.3390/molecules20069496
Received: 10 April 2015 / Accepted: 20 May 2015 / Published: 25 May 2015
Cited by 6 | PDF Full-text (2647 KB) | HTML Full-text | XML Full-text
Abstract
The present study aimed to investigate the effect of Eudragit® E/HCl (E-SD) on the degradation of sirolimus in simulated gastric fluid (pH 1.2) and to develop a new oral formulation of sirolimus using E-SD solid dispersions to enhance oral bioavailability. Sirolimus-loaded solid
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The present study aimed to investigate the effect of Eudragit® E/HCl (E-SD) on the degradation of sirolimus in simulated gastric fluid (pH 1.2) and to develop a new oral formulation of sirolimus using E-SD solid dispersions to enhance oral bioavailability. Sirolimus-loaded solid dispersions were fabricated by a spray drying process. A kinetic solubility test demonstrated that the sirolimus/E-SD/TPGS (1/8/1) solid dispersion had a maximum solubility of 196.7 μg/mL within 0.5 h that gradually decreased to 173.4 μg/mL after 12 h. According to the dissolution study, the most suitable formulation was the sirolimus/E-SD/TPGS (1/8/1) solid dispersion in simulated gastric fluid (pH 1.2), owing to enhanced stability and degree of supersaturation of E-SD and TPGS. Furthermore, pharmacokinetic studies in rats indicated that compared to the physical mixture and sirolimus/HPMC/TPGS (1/8/1) solid dispersion, the sirolimus/E-SD/TPGS (1/8/1) solid dispersion significantly improved oral absorption of sirolimus. E-SD significantly inhibited the degradation of sirolimus in a dose-dependent manner. E-SD also significantly inhibited the precipitation of sirolimus compared to hydroxypropylmethyl cellulose (HPMC). Therefore, the results from the present study suggest that the sirolimus-loaded E-SD/TPGS solid dispersion has great potential in clinical applications. Full article
(This article belongs to the collection Poorly Soluble Drugs)
Open AccessArticle Combine Use of Selected Schizosaccharomyces pombe and Lachancea thermotolerans Yeast Strains as an Alternative to theTraditional Malolactic Fermentation in Red Wine Production
Molecules 2015, 20(6), 9510-9523; doi:10.3390/molecules20069510
Received: 17 February 2015 / Revised: 11 May 2015 / Accepted: 12 May 2015 / Published: 26 May 2015
Cited by 25 | PDF Full-text (2223 KB) | HTML Full-text | XML Full-text
Abstract
Most red wines commercialized in the market use the malolactic fermentationprocess in order to ensure stability from a microbiological point of view. In this secondfermentation, malic acid is converted into L-lactic acid under controlled setups. Howeverthis process is not free from possible collateral
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Most red wines commercialized in the market use the malolactic fermentationprocess in order to ensure stability from a microbiological point of view. In this secondfermentation, malic acid is converted into L-lactic acid under controlled setups. Howeverthis process is not free from possible collateral effects that on some occasions produceoff-flavors, wine quality loss and human health problems. In warm viticulture regions suchas the south of Spain, the risk of suffering a deviation during the malolactic fermentationprocess increases due to the high must pH. This contributes to produce wines with highvolatile acidity and biogenic amine values. This manuscript develops a new red winemakingmethodology that consists of combining the use of two non-Saccharomyces yeast strains asan alternative to the traditional malolactic fermentation. In this method, malic acid is totallyconsumed by Schizosaccharomyces pombe, thus achieving the microbiological stabilizationobjective, while Lachancea thermotolerans produces lactic acid in order not to reduce andeven increase the acidity of wines produced from low acidity musts. This technique reducesthe risks inherent to the malolactic fermentation process when performed in warm regions.The result is more fruity wines that contain less acetic acid and biogenic amines than thetraditional controls that have undergone the classical malolactic fermentation. Full article
(This article belongs to the collection Wine Chemistry)
Open AccessArticle Pretreatment with Relaxin Does Not Restore NO-Mediated Modulation of Calcium Signal in Coronary Endothelial Cells Isolated from Spontaneously Hypertensive Rats
Molecules 2015, 20(6), 9524-9535; doi:10.3390/molecules20069524
Received: 18 March 2015 / Revised: 11 May 2015 / Accepted: 15 May 2015 / Published: 26 May 2015
Cited by 2 | PDF Full-text (717 KB) | HTML Full-text | XML Full-text
Abstract
We demonstrated that in coronary endothelial cells (RCEs) from normotensive Wistar Kyoto rats (WKY), the hormone relaxin (RLX) increases NO production and reduces calcium transients by a NO-related mechanism. Since an impairment of the NO pathway has been described in spontaneously hypertensive rats
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We demonstrated that in coronary endothelial cells (RCEs) from normotensive Wistar Kyoto rats (WKY), the hormone relaxin (RLX) increases NO production and reduces calcium transients by a NO-related mechanism. Since an impairment of the NO pathway has been described in spontaneously hypertensive rats (SHR), the present study was aimed at exploring RLX effects on RCEs from SHR, hypothesizing that RLX could restore calcium responsiveness to NO. RCEs were isolated from WKY and SHR. Calcium transients were evaluated by image analysis after the administration of angiotensin II or α-thrombin. Angiotensin II (1 µM) caused a prompt rise of [Ca2+]i in WKY and SHR RCEs and a rapid decrease, being the decay time higher in SHR than in WKY. NOS inhibition increased calcium transient in WKY, but not in SHR RCEs. Whereas RLX pretreatment (24 h, 60 ng/mL) was ineffective in SHR, it strongly reduced calcium transient in WKY in a NO-dependent way. A similar behavior was measured using 30 U/mL α-thrombin. The current study offers evidence that RLX cannot restore NO responsiveness in SHR, suggesting an accurate selection of patients eligible for RLX treatment of cardiovascular diseases. Full article
(This article belongs to the Special Issue Nitric Oxide (NO) Release Chemistry)
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Open AccessArticle The Effect of Phenol Composition on the Sensory Profile of Smoke Affected Wines
Molecules 2015, 20(6), 9536-9549; doi:10.3390/molecules20069536
Received: 16 March 2015 / Revised: 19 May 2015 / Accepted: 19 May 2015 / Published: 26 May 2015
PDF Full-text (1784 KB) | HTML Full-text | XML Full-text
Abstract
Vineyards exposed to wildfire generated smoke can produce wines with elevated levels of lignin derived phenols that have acrid, metallic and smoky aromas and flavour attributes. While a large number of phenols are present in smoke affected wines, the effect of smoke vegetation
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Vineyards exposed to wildfire generated smoke can produce wines with elevated levels of lignin derived phenols that have acrid, metallic and smoky aromas and flavour attributes. While a large number of phenols are present in smoke affected wines, the effect of smoke vegetation source on the sensory descriptors has not been reported. Here we report on a descriptive sensory analysis of wines made from grapes exposed to different vegetation sources of smoke to examine: (1) the effect vegetation source has on wine sensory attribute ratings and; (2) associations between volatile and glycoconjugated phenol composition and sensory attributes. Sensory attribute ratings were determined by a trained sensory panel and phenol concentrations determined by gas chromatography-mass spectroscopy. Analysis of variance, principal component analysis and partial least squares regressions were used to evaluate the interrelationships between the phenol composition and sensory attributes. The results showed that vegetation source of smoke significantly affected sensory attribute intensity, especially the taste descriptors. Differences in aroma and taste from smoke exposure were not limited to an elevation in a range of detractive descriptors but also a masking of positive fruit descriptors. Sensory differences due to vegetation type were driven by phenol composition and concentration. In particular, the glycoconjugates of 4-hydroxy-3-methoxybenzaldehyde (vanillin), 1-(4-hydroxy-3-methoxyphenyl)ethanone (acetovanillone), 4-hydroxy-3,5-dimethoxybenzaldehyde (syringaldehyde) and 1-(4-hydroxy-3,5-dimethoxyphenyl)ethanone (acetosyringone) concentrations were influential in separating the vegetation sources of smoke. It is concluded that the detractive aroma attributes of smoke affected wine, especially of smoke and ash, were associated with volatile phenols while the detractive flavour descriptors were correlated with glycoconjugated phenols. Full article
(This article belongs to the collection Wine Chemistry)
Open AccessCommunication Practical Radiosynthesis and Preclinical Neuroimaging of [11C]isradipine, a Calcium Channel Antagonist
Molecules 2015, 20(6), 9550-9559; doi:10.3390/molecules20069550
Received: 28 April 2015 / Revised: 19 May 2015 / Accepted: 20 May 2015 / Published: 26 May 2015
Cited by 1 | PDF Full-text (1179 KB) | HTML Full-text | XML Full-text
Abstract
In the interest of developing in vivo positron emission tomography (PET) probes for neuroimaging of calcium channels, we have prepared a carbon-11 isotopologue of a dihydropyridine Ca2+-channel antagonist, isradipine. Desmethyl isradipine (4-(benzo[c][1,2,5]oxadiazol-4-yl)-5-(isopropoxycarbonyl)-2,6-dimethyl-1,4-dihydropyridine -3-carboxylic acid) was reacted with [11
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In the interest of developing in vivo positron emission tomography (PET) probes for neuroimaging of calcium channels, we have prepared a carbon-11 isotopologue of a dihydropyridine Ca2+-channel antagonist, isradipine. Desmethyl isradipine (4-(benzo[c][1,2,5]oxadiazol-4-yl)-5-(isopropoxycarbonyl)-2,6-dimethyl-1,4-dihydropyridine -3-carboxylic acid) was reacted with [11C]CH3I in the presence of tetrabutylammonium hydroxide in DMF in an HPLC injector loop to produce the radiotracer in a good yield (6 ± 3% uncorrected radiochemical yield) and high specific activity (143 ± 90 GBq·µmol−1 at end-of-synthesis). PET imaging of normal rats revealed rapid brain uptake at baseline (0.37 ± 0.08% ID/cc (percent of injected dose per cubic centimeter) at peak, 15–60 s), which was followed by fast washout. After pretreatment with isradipine (2 mg·kg−1, i.p.), whole brain radioactivity uptake was diminished by 25%–40%. This preliminary study confirms that [11C]isradipine can be synthesized routinely for research studies and is brain penetrating. Further work on Ca2+-channel radiotracer development is planned. Full article
(This article belongs to the Special Issue Preparation of Radiopharmaceuticals and Their Use in Drug Development)
Open AccessArticle Comparative Studies on Polyphenolic Composition, Antioxidant and Diuretic Effects of Nigella sativa L. (Black Cumin) and Nigella damascena L. (Lady-in-a-Mist) Seeds
Molecules 2015, 20(6), 9560-9574; doi:10.3390/molecules20069560
Received: 20 April 2015 / Revised: 17 May 2015 / Accepted: 18 May 2015 / Published: 26 May 2015
Cited by 14 | PDF Full-text (730 KB) | HTML Full-text | XML Full-text
Abstract
This study was performed to evaluate the phenolic profile, antioxidant and diuretic effects of black cumin and lady-in-a-mist seeds. In the phenolic profile, differences between the two species are significant. Qualitative and quantitative analyses of the phenolic compounds were performed using a HPLC-UV/MS
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This study was performed to evaluate the phenolic profile, antioxidant and diuretic effects of black cumin and lady-in-a-mist seeds. In the phenolic profile, differences between the two species are significant. Qualitative and quantitative analyses of the phenolic compounds were performed using a HPLC-UV/MS method. Hyperoside was the only identified flavonoid glycoside (1.08 ± 0.01 μg∙g−1 dw plant material), in the N. damascena extract. Regarding the flavonol profile, kaempferol was identified before the hydrolysis, only in the N. sativa extract (6.06 ± 0.02 μg∙g−1 dw plant material) and quercetin only in N. damascena seeds (14.35 ± 0.02 μg∙g−1 dw plant material). The antioxidant potential of the two species was tested through several electron transfer assays, which indicated, excepting for the FRAP assay, N. damascena as exhibiting a higher free radical scavenging activity. The diuretic activity of the two extracts was tested using a rat-experimental model on acute diuresis. Administration of the ethanolic extract of N. sativa (100 mg∙kg−1) resulted in a significant increase in urine volume, although less than found with the reference drug; in addition N. damascena extract did not present a diuretic effect. In reference to the elimination of Na+, K+ and uric acid, the black cumin extract exhibited a higher natriuretic than kaluretic effect and a similar uricosuric effect with control and N. damascena. For N. damascena, the Na+/K+ ratio was sub unitary, but not due to an increasing of the kaluretic effect, but mostly to a decrease of Na+ excretion. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Reactivity of Amine/E(C6F5)3 (E = B, Al) Lewis Pairs toward Linear and Cyclic Acrylic Monomers: Hydrogenation vs. Polymerization
Molecules 2015, 20(6), 9575-9590; doi:10.3390/molecules20069575
Received: 29 April 2015 / Revised: 20 May 2015 / Accepted: 21 May 2015 / Published: 26 May 2015
Cited by 9 | PDF Full-text (1234 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
This work reveals the contrasting reactivity of amine/E(C6F5)3 (E = B, Al) Lewis pairs toward linear and cyclic acrylic monomers, methyl methacrylate (MMA) and biorenewable γ-methyl-α-methylene-γ-butyrolactone (γMMBL). While mixing of 2,2,6,6-tetramethylpiperidine (TMP) and B(C6F
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This work reveals the contrasting reactivity of amine/E(C6F5)3 (E = B, Al) Lewis pairs toward linear and cyclic acrylic monomers, methyl methacrylate (MMA) and biorenewable γ-methyl-α-methylene-γ-butyrolactone (γMMBL). While mixing of 2,2,6,6-tetramethylpiperidine (TMP) and B(C6F5)3 leads to a frustrated Lewis pair (FLP), Et3N reacts with B(C6F5)3 to form disproportionation products, ammonium hydridoborate ionic pair and iminium zwitterion. On the other hand, the stoichiometric reaction of either TMP or Et3N with Al(C6F5)3 leads to clean formation of a classic Lewis adduct (CLA). Neither TMP nor Et3N, when paired with E(C6F5)3, polymerizes MMA, but the Et3N/2B(C6F5)3 pair promotes transfer hydrogenation of MMA to form methyl isobutyrate. In contrast, the amine/E(C6F5)3 pairs promote rapid polymerization of γMMBL carrying the more reactive exocyclic methylene moiety, achieving full conversion in less than 3 min even at a low catalyst loading of 0.0625 mol %. TMP is more effective than Et3N for the polymerization when paired with either the borane or the alane, while the alane exhibits higher polymerization activity than the borane when paired with Et3N. Overall, the TMP/Al(C6F5)3 system exhibits the highest polymerization activity, achieving a maximum turn-over frequency of 96,000 h−1 at 0.125 mol % of catalyst loading, producing high molecular weight PγMMBL with Mn = 1.29 × 105 g∙mol−1. Full article
(This article belongs to the Special Issue The Reactivity of Frustrated Lewis Pairs)
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Open AccessArticle Synthesis, 18F-Radiolabelling and Biological Characterization of Novel Fluoroalkylated Triazine Derivatives for in Vivo Imaging of Phosphodiesterase 2A in Brain via Positron Emission Tomography
Molecules 2015, 20(6), 9591-9615; doi:10.3390/molecules20069591
Received: 17 April 2015 / Revised: 4 May 2015 / Accepted: 18 May 2015 / Published: 26 May 2015
Cited by 7 | PDF Full-text (2462 KB) | HTML Full-text | XML Full-text
Abstract
Phosphodiesterase 2A (PDE2A) is highly and specifically expressed in particular brain regions that are affected by neurological disorders and in certain tumors. Development of a specific PDE2A radioligand would enable molecular imaging of the PDE2A protein via positron emission tomography (PET). Herein we
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Phosphodiesterase 2A (PDE2A) is highly and specifically expressed in particular brain regions that are affected by neurological disorders and in certain tumors. Development of a specific PDE2A radioligand would enable molecular imaging of the PDE2A protein via positron emission tomography (PET). Herein we report on the syntheses of three novel fluoroalkylated triazine derivatives (TA24) and on the evaluation of their effect on the enzymatic activity of human PDE2A. The most potent PDE2A inhibitors were 18F-radiolabelled ([18F]TA3 and [18F]TA4) and investigated regarding their potential as PET radioligands for imaging of PDE2A in mouse brain. In vitro autoradiography on rat brain displayed region-specific distribution of [18F]TA3 and [18F]TA4, which is consistent with the expression pattern of PDE2A protein. Metabolism studies of both [18F]TA3 and [18F]TA4 in mice showed a significant accumulation of two major radiometabolites of each radioligand in brain as investigated by micellar radio-chromatography. Small-animal PET/MR studies in mice using [18F]TA3 revealed a constantly increasing uptake of activity in the non-target region cerebellum, which may be caused by the accumulation of brain penetrating radiometabolites. Hence, [18F]TA3 and [18F]TA4 are exclusively suitable for in vitro investigation of PDE2A. Nevertheless, further structural modification of these promising radioligands might result in metabolically stable derivatives. Full article
(This article belongs to the Special Issue Preparation of Radiopharmaceuticals and Their Use in Drug Development)
Open AccessArticle Xerogel-Sequestered Silanated Organochalcogenide Catalysts for Bromination with Hydrogen Peroxide and Sodium Bromide
Molecules 2015, 20(6), 9616-9639; doi:10.3390/molecules20069616
Received: 30 April 2015 / Accepted: 21 May 2015 / Published: 26 May 2015
Cited by 5 | PDF Full-text (1282 KB) | HTML Full-text | XML Full-text
Abstract
While H2O2 is a powerful oxidant, decomposing into environmentally benign H2O and O2, a catalyst is often required for reactions with H2O2 to proceed at synthetically useful rates. Organotellurium and organoselenium compounds catalyze
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While H2O2 is a powerful oxidant, decomposing into environmentally benign H2O and O2, a catalyst is often required for reactions with H2O2 to proceed at synthetically useful rates. Organotellurium and organoselenium compounds catalyze the oxidation of halide salts to hypohalous acids using H2O2. When sequestered into xerogel monoliths, the xerogel-chalcogenide combinations have demonstrated increased catalytic activity relative to the organochalcogen compound alone in solution for the oxidation of halide salts to hypohalous acids with H2O2. Diorganotellurides, diorganoselenides, and diorganodiselenides bearing triethoxysilane functionalities were sequestered into xerogel monoliths and their catalytic activity and longevity were investigated. The longevity of the catalyst-xerogel combinations was examined by isolating and recycling the catalyst-xerogel combination. It was found tellurium-containing catalyst 3 and selenium-containing catalyst 8 maintained their catalytic activity through three recycling trials and adding electron-donating substituents to catalyst 3 also increased the catalytic rate. The presence of organotellurium and organoselenium groups in the +4 oxidation state was determined by X-ray photoelectron spectroscopy. Full article
(This article belongs to the Special Issue Selenium Catalysts and Antioxidants)
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Open AccessArticle Multidisciplinary Approach to Determine the Optimal Time and Period for Extracting the Essential Oil from Mentha suaveolens Ehrh
Molecules 2015, 20(6), 9640-9655; doi:10.3390/molecules20069640
Received: 13 March 2015 / Revised: 15 May 2015 / Accepted: 18 May 2015 / Published: 26 May 2015
Cited by 7 | PDF Full-text (733 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A comprehensive study on essential oils (EOs) extracted from some Mentha suaveolens L. samples, collected in the countryside of Tarquinia, is reported. In this study, the procedure for essential oil preparation, in terms of harvesting and extraction time, was analyzed in detail for
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A comprehensive study on essential oils (EOs) extracted from some Mentha suaveolens L. samples, collected in the countryside of Tarquinia, is reported. In this study, the procedure for essential oil preparation, in terms of harvesting and extraction time, was analyzed in detail for the first time. The GC/MS analysis, carried out on 18 samples, revealed that piperitenone oxide (PO), the main essential oils’ chemical constituent, is primarily responsible for the related antifungal activity. Nevertheless, EOs with lower PO content indicate that other chemicals, such as para-cymenene, may participate in exerting the EOs’ antifungal effect. Furthermore, the bacterial reverse mutation assay highlighted lack of mutagenic effect in all tested samples. Analysis of the results indicated that for higher activity, the essential oils should be produced with 3 h maximum hydrodistillation, regardless of the harvesting time. Differently, the maximum essential oil yield can be obtained in August and the highest piperitenone oxide percentage is obtainable in July. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle A Herbal Formula HT048, Citrus unshiu and Crataegus pinnatifida, Prevents Obesity by Inhibiting Adipogenesis and Lipogenesis in 3T3-L1 Preadipocytes and HFD-Induced Obese Rats
Molecules 2015, 20(6), 9656-9670; doi:10.3390/molecules20069656
Received: 9 April 2015 / Revised: 15 April 2015 / Accepted: 18 April 2015 / Published: 26 May 2015
Cited by 6 | PDF Full-text (4049 KB) | HTML Full-text | XML Full-text
Abstract
HT048 is a combination composed of Crataegus pinnatifida leaf and Citrus unshiu peel extracts. This study aimed to investigate potential anti-obesity effect of the combination. The 3T3-L1 adipocytes were treated with different doses of HT048 and triglyceride accumulation, glycerol release and adipogenesis-related genes
[...] Read more.
HT048 is a combination composed of Crataegus pinnatifida leaf and Citrus unshiu peel extracts. This study aimed to investigate potential anti-obesity effect of the combination. The 3T3-L1 adipocytes were treated with different doses of HT048 and triglyceride accumulation, glycerol release and adipogenesis-related genes were analyzed. For in vivo study, male Sprague Dawley rats were divided according to experimental diets: the chow diet group, the high-fat diet (HFD) group, the HFD supplemented with orlistat group, the HFD supplemented with HT048 group (0.2% or 0.4%) for 12 weeks. We measured the body weight, serum lipid levels and the expression of genes involved lipid metabolism. HT048 treatment dose-dependently suppressed adipocyte differentiation and stimulated glycerol release. The expressions of PPARγ and C/EBPα mRNA were decreased by HT048 treatment in adipocytes. HT048 supplementation significantly reduced the body and fat weights in vivo. Serum lipid levels were significantly lower in the HT048 supplemented groups than those of the HFD group. Expression of the hepatic lipogenesis-related genes were decreased and expression of the β-oxidation-related genes were increased in rats fed HT048 compared to that of animals fed HFD. These results suggest that HT048 has a potential benefit in preventing obesity through the inhibition of lipogenesis and adipogenesis. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Purity Assessment of Aryltetralin Lactone Lignans by Quantitative 1H Nuclear Magnetic Resonance
Molecules 2015, 20(6), 9671-9685; doi:10.3390/molecules20069671
Received: 26 March 2015 / Accepted: 15 May 2015 / Published: 26 May 2015
Cited by 1 | PDF Full-text (1229 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In the present work, a quantitative 1H Nuclear Magnetic Resonance (qHNMR) was established for purity assessment of six aryltetralin lactone lignans. The validation of the method was carried out, including specificity, selectivity, linearity, accuracy, precision, and robustness. Several experimental parameters were optimized,
[...] Read more.
In the present work, a quantitative 1H Nuclear Magnetic Resonance (qHNMR) was established for purity assessment of six aryltetralin lactone lignans. The validation of the method was carried out, including specificity, selectivity, linearity, accuracy, precision, and robustness. Several experimental parameters were optimized, including relaxation delay (D1), scan numbers (NS), and pulse angle. 1,4-Dinitrobenzene was used as internal standard (IS), and deuterated dimethyl sulfoxide (DMSO-d6) as the NMR solvent. The purities were calculated by the area ratios of H-2,6 from target analytes vs. aromatic protons from IS. Six aryltetralin lactone lignans (deoxypodophyllotoxin, podophyllotoxin, 4-demethylpodophyllotoxin, podophyllotoxin-7′-O-β-d-glucopyranoside, 4-demethylpodophyllotoxin-7′-O-β-d-glucopyranoside, and 6′′-acetyl-podophyllotoxin-7′-O-β -d-glucopyranoside) were analyzed. The analytic results of qHNMR were further validated by high performance liquid chromatography (HPLC). Therefore, the qHNMR method was a rapid, accurate, reliable tool for monitoring the purity of aryltetralin lactone lignans. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Green Extraction of Antioxidants from Different Varieties of Red Grape Pomace
Molecules 2015, 20(6), 9686-9702; doi:10.3390/molecules20069686
Received: 19 March 2015 / Accepted: 13 May 2015 / Published: 26 May 2015
Cited by 10 | PDF Full-text (965 KB) | HTML Full-text | XML Full-text
Abstract
The extraction yield, phenolic content, anthocyanin content and antioxidant activity of extracts from different varieties of red grapes, Cabernet Sauvignon, Merlot, Petit Verdot, Syrah, Tempranillo and Tintilla, using pressurized green solvents have been analyzed. Two techniques were studied and compared: supercritical fluid extraction
[...] Read more.
The extraction yield, phenolic content, anthocyanin content and antioxidant activity of extracts from different varieties of red grapes, Cabernet Sauvignon, Merlot, Petit Verdot, Syrah, Tempranillo and Tintilla, using pressurized green solvents have been analyzed. Two techniques were studied and compared: supercritical fluid extraction (SFE) with CO2 + 20% ethanol and pressurized liquid extraction (PLE) with either ethanol, water or an ethanol/water mixture as the extraction solvents. The Petit Verdot variety allowed the highest global and phenolic yield, and antioxidant activity. The best conditios for PLE obtained from the experimental design and kinetic study were 50% ethanol/water as the pressurized solvent at 90 bar, 120 °C, a flow rate of 5 g/min and, an extraction time of 90 min. A statistical analysis of variance has been performed and it was found that temperature is the only variable that has a statistical influence on the extraction yield. The antioxidant activity levels of the extracts are very promising and they are similar to those obtained with the antioxidant tocopherol. Full article
(This article belongs to the Special Issue New Technologies for the Recovery of Natural Products)
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Open AccessArticle Theoretical Verification of Photoelectrochemical Water Oxidation Using Nanocrystalline TiO2 Electrodes
Molecules 2015, 20(6), 9732-9744; doi:10.3390/molecules20069732
Received: 31 December 2014 / Accepted: 12 May 2015 / Published: 27 May 2015
Cited by 1 | PDF Full-text (2857 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Mesoscopic anatase nanocrystalline TiO2 (nc-TiO2) electrodes play effective and efficient catalytic roles in photoelectrochemical (PEC) H2O oxidation under short circuit energy gap excitation conditions. Interfacial molecular orbital structures of (H2O)3 &OH(TiO2)9H
[...] Read more.
Mesoscopic anatase nanocrystalline TiO2 (nc-TiO2) electrodes play effective and efficient catalytic roles in photoelectrochemical (PEC) H2O oxidation under short circuit energy gap excitation conditions. Interfacial molecular orbital structures of (H2O)3 &OH(TiO2)9H as a stationary model under neutral conditions and the radical-cation model of [(H2O)3&OH(TiO2)9H]+ as a working nc-TiO2 model are simulated employing a cluster model OH(TiO2)9H (Yamashita/Jono’s model) and a H2O cluster model of (H2O)3 to examine excellent H2O oxidation on nc-TiO2 electrodes in PEC cells. The stationary model, (H2O)3&OH(TiO2)9H reveals that the model surface provides catalytic H2O binding sites through hydrogen bonding, van der Waals and Coulombic interactions. The working model, [(H2O)3&OH(TiO2)9H]+ discloses to have a very narrow energy gap (0.3 eV) between HOMO and LUMO potentials, proving that PEC nc-TiO2 electrodes become conductive at photo-irradiated working conditions. DFT-simulation of stepwise oxidation of a hydroxide ion cluster model of OH(H2O)3, proves that successive two-electron oxidation leads to hydroxyl radical clusters, which should give hydrogen peroxide as a precursor of oxygen molecules. Under working bias conditions of PEC cells, nc-TiO2 electrodes are now verified to become conductive by energy gap photo-excitation and the electrode surface provides powerful oxidizing sites for successive H2O oxidation to oxygen via hydrogen peroxide. Full article
(This article belongs to the Special Issue Photocatalysis) Printed Edition available
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Open AccessArticle Synthesis and Biological Evaluation of N-Alkoxyphenyl-3-hydroxynaphthalene-2-carboxanilides
Molecules 2015, 20(6), 9767-9787; doi:10.3390/molecules20069767
Received: 26 April 2015 / Accepted: 19 May 2015 / Published: 27 May 2015
Cited by 7 | PDF Full-text (805 KB) | HTML Full-text | XML Full-text
Abstract
A series of fifteen new N-alkoxyphenylanilides of 3-hydroxynaphthalene-2-carboxylic acid was prepared and characterized. Primary in vitro screening of the synthesized compounds was performed against Staphylococcus aureus, three methicillin-resistant S. aureus strains, Mycobacterium tuberculosis H37Ra and M. avium subsp. paratuberculosis. Some
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A series of fifteen new N-alkoxyphenylanilides of 3-hydroxynaphthalene-2-carboxylic acid was prepared and characterized. Primary in vitro screening of the synthesized compounds was performed against Staphylococcus aureus, three methicillin-resistant S. aureus strains, Mycobacterium tuberculosis H37Ra and M. avium subsp. paratuberculosis. Some of the tested compounds showed antibacterial and antimycobacterial activity against the tested strains comparable with or higher than that of the standards ampicillin or rifampicin. 3-Hydroxy-N-(2-propoxyphenyl)naphthalene-2-carboxamide and N-[2-(but-2-yloxy)-phenyl]-3-hydroxynaphthalene-2-carboxamide had MIC = 12 µM against all methicillin-resistant S. aureus strains; thus their activity is 4-fold higher than that of ampicillin. The second mentioned compound as well as 3-hydroxy-N-[3-(prop-2-yloxy)phenyl]-naphthalene-2-carboxamide had MICs = 23 µM and 24 µM against M. tuberculosis respectively. N-[2-(But-2-yloxy)phenyl]-3-hydroxynaphthalene-2-carboxamide demonstrated higher activity against M. avium subsp. paratuberculosis than rifampicin. Screening of the cytotoxicity of the most effective antimycobacterial compounds was performed using THP-1 cells, and no significant lethal effect was observed for the most potent compounds. The compounds were additionally tested for their activity related to inhibition of photosynthetic electron transport (PET) in spinach (Spinacia oleracea L.) chloroplasts. N-(3-Ethoxyphenyl)-3-hydroxynaphthalene-2-carboxamide (IC50 = 4.5 µM) was the most active PET inhibitor. The structure-activity relationships are discussed. Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessArticle Synthesis, Characterization and Biological Studies of Metal(II) Complexes of (3E)-3-[(2-{(E)-[1-(2,4-Dihydroxyphenyl) ethylidene]amino}ethyl)imino]-1-phenylbutan-1-one Schiff Base
Molecules 2015, 20(6), 9788-9802; doi:10.3390/molecules20069788
Received: 3 April 2015 / Accepted: 15 May 2015 / Published: 27 May 2015
Cited by 16 | PDF Full-text (1159 KB) | HTML Full-text | XML Full-text
Abstract
Co(II), Ni(II), Zn(II) and Cu(II) complexes of (3E)-3-[(2-{(E)-[1-(2,4-dihydroxyphenyl)ethylidene]amino}ethyl)imino]-1-phenylbutan-1-one (DEPH2) derived from ethylenediamine, 2′,4′-dihydroxyacetophenone and 1-phenylbutane-1,3-dione have been synthesized and characterized by elemental analysis, FTIR, UV-Visible spectroscopy, and screened to establish their potential as antibacterial agents, antioxidants and
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Co(II), Ni(II), Zn(II) and Cu(II) complexes of (3E)-3-[(2-{(E)-[1-(2,4-dihydroxyphenyl)ethylidene]amino}ethyl)imino]-1-phenylbutan-1-one (DEPH2) derived from ethylenediamine, 2′,4′-dihydroxyacetophenone and 1-phenylbutane-1,3-dione have been synthesized and characterized by elemental analysis, FTIR, UV-Visible spectroscopy, and screened to establish their potential as antibacterial agents, antioxidants and DPPH radical scavengers. The FTIR spectra showed that the ligand behaves as a dibasic tetradentate ligand with the dioxygen-dinitrogen donor atom system oriented towards the central metal ion. The analytical and spectroscopic data suggest a square planar geometry for Cu(II) and Ni(II) complexes and an octahedral geometry for the Co(II) complex. The ligand and their metal complexes were screened for antibacterial activity against Gram (+) and Gram (−) bacteria by the agar well diffusion method. In addition, the antioxidant activities of the complexes were also investigated through their scavenging effect on DPPH and ABTS radicals. The obtained IC50 value of the DPPH activity for the copper complex (2.08 ± 0.47 µM) and that of the ABTS activity for the copper complex (IC50 = 2.11 + 1.69 µM) were higher than the values obtained for the other compounds. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Volatile Profile of Cashew Apple Juice Fibers from Different Production Steps
Molecules 2015, 20(6), 9803-9815; doi:10.3390/molecules20069803
Received: 28 November 2014 / Accepted: 26 January 2015 / Published: 27 May 2015
Cited by 2 | PDF Full-text (791 KB) | HTML Full-text | XML Full-text
Abstract
This study aimed to determine the volatile profile of cashew apple fibers to verify which compounds are still present after successive washings and thus might be responsible for the undesirable remaining cashew-like aroma present in this co-product, which is used to formulate food
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This study aimed to determine the volatile profile of cashew apple fibers to verify which compounds are still present after successive washings and thus might be responsible for the undesirable remaining cashew-like aroma present in this co-product, which is used to formulate food products like vegetarian burgers and cereal bars. Fibers were obtained from cashew apple juice processing and washed five times in an expeller press. Compounds were analyzed by the headspace solid-phase micro extraction technique (HS-SPME) and gas chromatography-mass spectrometry (GC-MS), using a DB-5 column. Sensory analysis was also performed to compare the intensity of the cashew-like aroma of the fibers with the original juice. Altogether, 80 compounds were detected, being esters and terpenes the major chemical classes. Among the identified substances, 14 were classified as odoriferous in the literature, constituting the matrix used in the Principal Component Analysis (PCA). Odoriferous esters were substantially reduced, but many compounds were extracted by the strength used in the expeller press and remained until the last wash. Among them are the odoriferous compounds ethyl octanoate, γ-dodecalactone, (E)-2-decenal, copaene, and caryophyllene that may contribute for the mild but still perceptible cashew apple aroma in the fibers that have been pressed and washed five times. Development of a deodorization process should include reduction of pressing force and stop at the second wash, to save water and energy, thus reducing operational costs and contributing to process sustainability. Full article
(This article belongs to the Special Issue Aromas and Volatiles of Fruits)
Open AccessArticle Synthesis of S-Layer Conjugates and Evaluation of Their Modifiability as a Tool for the Functionalization and Patterning of Technical Surfaces
Molecules 2015, 20(6), 9847-9861; doi:10.3390/molecules20069847
Received: 26 January 2015 / Accepted: 20 May 2015 / Published: 27 May 2015
Cited by 2 | PDF Full-text (1349 KB) | HTML Full-text | XML Full-text
Abstract
Chemical functional groups of surface layer (S-layer) proteins were chemically modified in order to evaluate the potential of S-layer proteins for the introduction of functional molecules. S-layer proteins are structure proteins that self-assemble into regular arrays on surfaces. One general feature of S-layer
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Chemical functional groups of surface layer (S-layer) proteins were chemically modified in order to evaluate the potential of S-layer proteins for the introduction of functional molecules. S-layer proteins are structure proteins that self-assemble into regular arrays on surfaces. One general feature of S-layer proteins is their high amount of carboxylic and amino groups. These groups are potential targets for linking functional molecules, thus producing reactive surfaces. In this work, these groups were conjugated with the amino acid tryptophan. In another approach, SH-groups were chemically inserted in order to extend the spectrum of modifiable groups. The amount of modifiable carboxylic groups was further evaluated by potentiometric titration in order to evaluate the potential efficiency of S-layer proteins to work as matrix for bioconjugations. The results proved that S-layer proteins can work as effective matrices for the conjugation of different molecules. The advantage of using chemical modification methods over genetic methods lies in its versatile usage enabling the attachment of biomolecules, as well as fluorescent dyes and inorganic molecules. Together with their self-assembling properties, S-layer proteins are suitable as targets for bioconjugates, thus enabling a nanostructuring and bio-functionalization of surfaces, which can be used for different applications like biosensors, filter materials, or (bio)catalytic surfaces. Full article
(This article belongs to the Special Issue Bioconjugations)
Open AccessArticle Pyrrole-Pyridine and Pyrrole-Naphthyridine Hosts for Anion Recognition
Molecules 2015, 20(6), 9862-9878; doi:10.3390/molecules20069862
Received: 14 April 2015 / Revised: 21 May 2015 / Accepted: 22 May 2015 / Published: 27 May 2015
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Abstract
The association constants of the complexes formed by two hosts containing pyrrole, amide and azine (pyridine and 1,8-naphthyridine) groups and six guests, all monoanions (Cl, CH3CO2, NO3, H2PO4,
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The association constants of the complexes formed by two hosts containing pyrrole, amide and azine (pyridine and 1,8-naphthyridine) groups and six guests, all monoanions (Cl, CH3CO2, NO3, H2PO4, BF4, PF6), have been determined using NMR titrations. The X-ray crystal structure of the host N2,N5-bis(6-methylpyridin-2-yl)-3,4-diphenyl-1H-pyrrole- 2,5-dicarboxamide (1) has been solved (P21/c monoclinic space group). B3LYP/6-31G(d,p) and calculations were carried out in an attempt to rationalize the trends observed in the experimental association constants. Full article
(This article belongs to the Special Issue Molecular Recognition)
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Open AccessArticle Cytotoxicity of the Urokinase-Plasminogen Activator Inhibitor Carbamimidothioic Acid (4-Boronophenyl) Methyl Ester Hydrobromide (BC-11) on Triple-Negative MDA-MB231 Breast Cancer Cells
Molecules 2015, 20(6), 9879-9889; doi:10.3390/molecules20069879
Received: 4 March 2015 / Revised: 19 May 2015 / Accepted: 25 May 2015 / Published: 28 May 2015
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Abstract
BC-11 is an easily synthesized simple thiouronium-substituted phenylboronic acid, which has been shown to be cytotoxic on triple negative MDA-MB231 breast cancer cells by inducing a perturbation of cell cycle when administered at a concentration equal to its ED50 at 72 h
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BC-11 is an easily synthesized simple thiouronium-substituted phenylboronic acid, which has been shown to be cytotoxic on triple negative MDA-MB231 breast cancer cells by inducing a perturbation of cell cycle when administered at a concentration equal to its ED50 at 72 h (117 μM). Exposure of cells to BC-11, either pre-absorbed with a soluble preparation of the N-terminal fragment of urokinase-plasminogen activator (uPa), or in co-treatment with two different EGFR inhibitors, indicated that: (i) BC-11 acts via binding to the N-terminus of the enzyme where uPa- and EGF receptor-recognizing sites are present, thereby abrogating the growth-sustaining effect resulting from receptor binding; and (ii) the co-presence of the EGFR inhibitor PD153035 potentiates BC-11’s cytotoxicity. Exposure of cells to a higher concentration of BC-11 corresponding to its ED75 at 72 h (250 μM) caused additional impairment of mitochondrial activity, the production of reactive oxygen species and promotion of apoptosis. Therefore, BC-11 treatment appears to show potential for the development of this class of compounds in the prevention and/or therapy of “aggressive” breast carcinoma. Full article
(This article belongs to the Special Issue Recent Advances in Boron Chemistry)
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Open AccessArticle Chelation-Assisted Substrate-Controlled Asymmetric Lithiation-Allylboration of Chiral Carbamate 1,2,4-Butanetriol Acetonide
Molecules 2015, 20(6), 9890-9905; doi:10.3390/molecules20069890
Received: 5 April 2015 / Revised: 19 May 2015 / Accepted: 20 May 2015 / Published: 28 May 2015
PDF Full-text (807 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The lithiation of 2-(2,2-dimethyl-1,3-dioxolan-4-yl)ethyl diisopropylcarbamate (1) is achieved freely by sec-butyllithium in diethylether with high lk-diastereoselectivity: the bicyclic chelate complexes 3a and 3b are reacted with electrophiles to form optically active precursors 4a and 4b with >95% diastereoselectivity. In
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The lithiation of 2-(2,2-dimethyl-1,3-dioxolan-4-yl)ethyl diisopropylcarbamate (1) is achieved freely by sec-butyllithium in diethylether with high lk-diastereoselectivity: the bicyclic chelate complexes 3a and 3b are reacted with electrophiles to form optically active precursors 4a and 4b with >95% diastereoselectivity. In addition, tertiary diamines can undergo an external complexation in contest with the internal oxygen ligand, leading to improved stereoselectivities. The further reactions of lithiated carbamates with trans alkenyl-9-BBN derivatives after 1,2 metallate rearrangements, gave the key intermediate α-substituted allylic boranes 7. Subsequent allylboration of aldehydes gave (Z)-anti-homoallylic alcohols 8 in good yield and excellent d.r. Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessCommunication Reactivity of Aryl Halides for Reductive Dehalogenation in (Sea)water Using Polymer-Supported Terpyridine Palladium Catalyst
Molecules 2015, 20(6), 9906-9914; doi:10.3390/molecules20069906
Received: 18 March 2015 / Accepted: 26 May 2015 / Published: 28 May 2015
Cited by 2 | PDF Full-text (693 KB) | HTML Full-text | XML Full-text
Abstract
A polymer-supported terpyridine palladium complex was prepared. The complex was found to promote hydrodechlorination of aryl chlorides with potassium formate in seawater. Generally, reductive cleavage of aryl chlorides using transition metal catalysts is more difficult than that of aryl bromides and iodides (reactivity:
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A polymer-supported terpyridine palladium complex was prepared. The complex was found to promote hydrodechlorination of aryl chlorides with potassium formate in seawater. Generally, reductive cleavage of aryl chlorides using transition metal catalysts is more difficult than that of aryl bromides and iodides (reactivity: I > Br > Cl); however, the results obtained did not follow the general trend. Therefore, we investigated the reaction inhibition agents and found a method to remove these inhibitors. The polymeric catalysts showed high catalytic activity and high reusability for transfer reduction in seawater. Full article
(This article belongs to the Special Issue Organic Synthesis on Solid Phase)
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Open AccessArticle Synthesis and Characterization of Two Sulfonated Resorcinarenes: A New Example of a Linear Array of Sodium Centers and Macrocycles
Molecules 2015, 20(6), 9915-9928; doi:10.3390/molecules20069915
Received: 5 March 2015 / Revised: 6 May 2015 / Accepted: 7 May 2015 / Published: 28 May 2015
Cited by 3 | PDF Full-text (1465 KB) | HTML Full-text | XML Full-text
Abstract
Two sulfonated resorcinarenes were synthesized by reacting C-tetra(butyl) resorcinarene or C-tetra(2-(methylthio)ethyl)resorcinarene with formaldehyde in the presence of sodium sulfite. Their structures were determined via FT-IR, 1H-NMR, 13C-NMR and mass spectrometry. Thermal gravimetric analyses of the derivatives were also carried
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Two sulfonated resorcinarenes were synthesized by reacting C-tetra(butyl) resorcinarene or C-tetra(2-(methylthio)ethyl)resorcinarene with formaldehyde in the presence of sodium sulfite. Their structures were determined via FT-IR, 1H-NMR, 13C-NMR and mass spectrometry. Thermal gravimetric analyses of the derivatives were also carried out and revealed the presence of water molecules in the solid state. The sulfonated product of C-tetra(butyl)resorcinarene was characterized by an X-ray crystal structure determination. The asymmetric unit contains eight molecules of water and two of acetone, and analysis indicated that sulfonated resorcinarene prefers a cone configuration (rccc conformation) in the solid state. In the crystal array, classical hydrogen bond interactions O-H···O and intermolecular contacts were observed. In the crystal packing, a linear array of capsules of sulfonated resorcinarenes was generated for a chain of sodium atoms and sulfonate groups. Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessArticle Potential Amoebicidal Activity of Hydrazone Derivatives: Synthesis, Characterization, Electrochemical Behavior, Theoretical Study and Evaluation of the Biological Activity
Molecules 2015, 20(6), 9929-9948; doi:10.3390/molecules20069929
Received: 18 March 2015 / Accepted: 24 April 2015 / Published: 29 May 2015
Cited by 5 | PDF Full-text (1908 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Four new hydrazones were synthesized by the condensation of the selected hydrazine and the appropriate nitrobenzaldehyde. A complete characterization was done employing 1H- and 13C-NMR, electrochemical techniques and theoretical studies. After the characterization and electrochemical analysis of each compound, amoebicidal activity
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Four new hydrazones were synthesized by the condensation of the selected hydrazine and the appropriate nitrobenzaldehyde. A complete characterization was done employing 1H- and 13C-NMR, electrochemical techniques and theoretical studies. After the characterization and electrochemical analysis of each compound, amoebicidal activity was tested in vitro against the HM1:IMSS strain of Entamoeba histolytica. The results showed the influence of the nitrobenzene group and the hydrazone linkage on the amoebicidal activity. meta-Nitro substituted compound 2 presents a promising amoebicidal activity with an IC50 = 0.84 μM, which represents a 7-fold increase in cell growth inhibition potency with respect to metronidazole (IC50 = 6.3 μM). Compounds 1, 3, and 4 show decreased amoebicidal activity, with IC50 values of 7, 75 and 23 µM, respectively, as a function of the nitro group position on the aromatic ring. The observed differences in the biological activity could be explained not only by the redox potential of the molecules, but also by their capacity to participate in the formation of intra- and intermolecular hydrogen bonds. Redox potentials as well as the amoebicidal activity can be described with parameters obtained from the DFT analysis. Full article
(This article belongs to the Special Issue Antiparasitic Agents)
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Open AccessArticle Microwave-Assisted Resolution of α-Lipoic Acid Catalyzed by an Ionic Liquid Co-Lyophilized Lipase
Molecules 2015, 20(6), 9949-9960; doi:10.3390/molecules20069949
Received: 17 April 2015 / Revised: 18 May 2015 / Accepted: 19 May 2015 / Published: 29 May 2015
Cited by 2 | PDF Full-text (728 KB) | HTML Full-text | XML Full-text
Abstract
The combination of the ionic liquid co-lyophilized lipase and microwave irradiation was used to improve enzyme performance in enantioselective esterification of α-lipoic acid. Effects of various reaction conditions on enzyme activity and enantioselectivity were investigated. Under optimal condition, the highest enantioselectivity (E
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The combination of the ionic liquid co-lyophilized lipase and microwave irradiation was used to improve enzyme performance in enantioselective esterification of α-lipoic acid. Effects of various reaction conditions on enzyme activity and enantioselectivity were investigated. Under optimal condition, the highest enantioselectivity (E = 41.2) was observed with a high enzyme activity (178.1 μmol/h/mg) when using the ionic liquid co-lyophilized lipase with microwave assistance. Furthermore, the ionic liquid co-lyophilized lipase exhibited excellent reusability under low power microwave. Full article
(This article belongs to the collection Recent Advances in Organocatalysis)
Open AccessArticle Interplay between Beryllium Bonds and Anion-π Interactions in BeR2:C6X6:Y Complexes (R = H, F and Cl, X = H and F, and Y = Cl and Br)
Molecules 2015, 20(6), 9961-9976; doi:10.3390/molecules20069961
Received: 22 April 2015 / Revised: 23 May 2015 / Accepted: 26 May 2015 / Published: 29 May 2015
Cited by 6 | PDF Full-text (1342 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A theoretical study of the beryllium bonds in BeR2:C6X6 (R = H, F, Cl and X = H and F) has been carried out by means of MP2/aug′-cc-pVDZ computational methods. In addition, the ternary complexes BeR2:C
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A theoretical study of the beryllium bonds in BeR2:C6X6 (R = H, F, Cl and X = H and F) has been carried out by means of MP2/aug′-cc-pVDZ computational methods. In addition, the ternary complexes BeR2:C6X6:Y (Y = Cl and Br) have been analyzed. Geometric, energetic and electronic aspects of the complexes have been taken into account. All the parameters analyzed provide a clear indication of favorable cooperativity in both interactions observed, beryllium bond and aromatic ring:anion interaction. Full article
(This article belongs to the Special Issue Noncovalent pi-Interactions)
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Open AccessArticle DockBench: An Integrated Informatic Platform Bridging the Gap between the Robust Validation of Docking Protocols and Virtual Screening Simulations
Molecules 2015, 20(6), 9977-9993; doi:10.3390/molecules20069977
Received: 31 March 2015 / Revised: 5 May 2015 / Accepted: 21 May 2015 / Published: 29 May 2015
Cited by 12 | PDF Full-text (1203 KB) | HTML Full-text | XML Full-text
Abstract
Virtual screening (VS) is a computational methodology that streamlines the drug discovery process by reducing costs and required resources through the in silico identification of potential drug candidates. Structure-based VS (SBVS) exploits knowledge about the three-dimensional (3D) structure of protein targets and uses
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Virtual screening (VS) is a computational methodology that streamlines the drug discovery process by reducing costs and required resources through the in silico identification of potential drug candidates. Structure-based VS (SBVS) exploits knowledge about the three-dimensional (3D) structure of protein targets and uses the docking methodology as search engine for novel hits. The success of a SBVS campaign strongly depends upon the accuracy of the docking protocol used to select the candidates from large chemical libraries. The identification of suitable protocols is therefore a crucial step in the setup of SBVS experiments. Carrying out extensive benchmark studies, however, is usually a tangled task that requires users’ proficiency in handling different file formats and philosophies at the basis of the plethora of existing software packages. We present here DockBench 1.0, a platform available free of charge that eases the pipeline by automating the entire procedure, from docking benchmark to VS setups. In its current implementation, DockBench 1.0 handles seven docking software packages and offers the possibility to test up to seventeen different protocols. The main features of our platform are presented here and the results of the benchmark study of human Checkpoint kinase 1 (hChk1) are discussed as validation test. Full article
(This article belongs to the Special Issue Molecular Docking in Drug Design)
Open AccessArticle Three New Sesquiterpene Aryl Esters from the Mycelium of Armillaria mellea
Molecules 2015, 20(6), 9994-10003; doi:10.3390/molecules20069994
Received: 9 April 2015 / Revised: 25 May 2015 / Accepted: 26 May 2015 / Published: 29 May 2015
Cited by 4 | PDF Full-text (717 KB) | HTML Full-text | XML Full-text
Abstract
Three new sesquiterpene aryl esters and eight known compounds were isolated from the EtOH extract of the mycelium of Armillaria mellea. The structures of new compounds were established by analysis of their spectroscopic data. Some of the isolates showed cytotoxicity to a
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Three new sesquiterpene aryl esters and eight known compounds were isolated from the EtOH extract of the mycelium of Armillaria mellea. The structures of new compounds were established by analysis of their spectroscopic data. Some of the isolates showed cytotoxicity to a variety of cancer cell lines, including MCF-7, H460, HT-29, and CEM. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Synthesis and Physicochemical Characterization of the Impurities of Pemetrexed Disodium, an Anticancer Drug
Molecules 2015, 20(6), 10004-10031; doi:10.3390/molecules200610004
Received: 30 April 2015 / Revised: 25 May 2015 / Accepted: 26 May 2015 / Published: 29 May 2015
Cited by 1 | PDF Full-text (984 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A physicochemical characterization of the process-related impurities associated with the synthesis of pemetrexed disodium was performed. The possibility of pemetrexed impurities forming has been mentioned in literature, but no study on their structure has been published yet. This paper describes the development of
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A physicochemical characterization of the process-related impurities associated with the synthesis of pemetrexed disodium was performed. The possibility of pemetrexed impurities forming has been mentioned in literature, but no study on their structure has been published yet. This paper describes the development of the synthesis methods for these compounds and discusses their structure elucidation on the basis of two-dimensional NMR experiments and MS data. The identification of these impurities should be useful for the quality control during the production of the pemetrexed disodium salt. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Computational Study of Symmetric Methylation on Histone Arginine Catalyzed by Protein Arginine Methyltransferase PRMT5 through QM/MM MD and Free Energy Simulations
Molecules 2015, 20(6), 10032-10046; doi:10.3390/molecules200610032
Received: 3 March 2015 / Revised: 18 May 2015 / Accepted: 25 May 2015 / Published: 29 May 2015
Cited by 5 | PDF Full-text (2407 KB) | HTML Full-text | XML Full-text
Abstract
Protein arginine methyltransferases (PRMTs) catalyze the transfer of the methyl group from S-adenosyl-l-methionine (AdoMet) to arginine residues. There are three types of PRMTs (I, II and III) that produce different methylation products, including asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA) and monomethylarginine (MMA).
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Protein arginine methyltransferases (PRMTs) catalyze the transfer of the methyl group from S-adenosyl-l-methionine (AdoMet) to arginine residues. There are three types of PRMTs (I, II and III) that produce different methylation products, including asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA) and monomethylarginine (MMA). Since these different methylations can lead to different biological consequences, understanding the origin of product specificity of PRMTs is of considerable interest. In this article, the quantum mechanical/molecular mechanical (QM/MM) molecular dynamics (MD) and free energy simulations are performed to study SDMA catalyzed by the Type II PRMT5 on the basis of experimental observation that the dimethylated product is generated through a distributive fashion. The simulations have identified some important interactions and proton transfers during the catalysis. Similar to the cases involving Type I PRMTs, a conserved Glu residue (Glu435) in PRMT5 is suggested to function as general base catalyst based on the result of the simulations. Moreover, our results show that PRMT5 has an energetic preference for the first methylation on Nη1 followed by the second methylation on a different ω-guanidino nitrogen of arginine (Nη2).The first and second methyl transfers are estimated to have free energy barriers of 19–20 and 18–19 kcal/mol respectively. The computer simulations suggest a distinctive catalytic mechanism of symmetric dimethylation that seems to be different from asymmetric dimethylation. Full article
Open AccessArticle A 1H-NMR-Based Metabonomic Study on the Anti-Depressive Effect of the Total Alkaloid of Corydalis Rhizoma
Molecules 2015, 20(6), 10047-10064; doi:10.3390/molecules200610047
Received: 12 March 2015 / Revised: 13 May 2015 / Accepted: 26 May 2015 / Published: 29 May 2015
Cited by 6 | PDF Full-text (1628 KB) | HTML Full-text | XML Full-text
Abstract
Corydalis Rhizoma, named YuanHu in China, is the dried tuber of Corydalis yanhusuo W.T. Wang which is used in Traditional Chinese Medicine for pain relief and blood activation. Previous pharmacological studies showed that apart from analgesics, the alkaloids from YuanHu may be useful
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Corydalis Rhizoma, named YuanHu in China, is the dried tuber of Corydalis yanhusuo W.T. Wang which is used in Traditional Chinese Medicine for pain relief and blood activation. Previous pharmacological studies showed that apart from analgesics, the alkaloids from YuanHu may be useful in the therapy of depression by acting on the GABA, dopamine and benzodiazepine receptors. In this study, the antidepressive effect of the total alkaloid of YuanHu (YHTA) was investigated in a chronic unpredictable mild stress (CUMS) rat model using 1H-NMR-based metabonomics. Plasma metabolic profiles were analyzed and multivariate data analysis was applied to discover the metabolic biomarkers in CUMS rats. Thirteen biomarkers of CUMS-introduced depression were identified, which are myo-inositol, glycerol, glycine, creatine, glutamine, glutamate, β-glucose, α-glucose, acetoacetate, 3-hydroxybutyrate, leucine and unsaturated lipids (L7, L9). Moreover, a metabolic network of the potential biomarkers in plasma perturbed by CUMS was detected. After YHTA treatment, clear separation between the model group and YHTA-treated group was achieved. The levels of all the abnormal metabolites mentioned above showed a tendency of restoration to normal levels. The results demonstrated the therapeutic efficacy of YHTA against depression and suggested that NMR-based metabolomics can provide a simple and easy tool for the evaluation of herbal therapeutics. Full article
(This article belongs to the Special Issue Applications of Metabolomics within Natural Products Chemistry)
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Open AccessArticle Comparison of Fruits of Forsythia suspensa at Two Different Maturation Stages by NMR-Based Metabolomics
Molecules 2015, 20(6), 10065-10081; doi:10.3390/molecules200610065
Received: 10 March 2015 / Revised: 20 May 2015 / Accepted: 26 May 2015 / Published: 29 May 2015
Cited by 9 | PDF Full-text (2260 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Forsythiae Fructus (FF), the dried fruit of Forsythia suspensa, has been widely used as a heat-clearing and detoxifying herbal medicine in China. Green FF (GF) and ripe FF (RF) are fruits of Forsythia suspensa at different maturity stages collected about a month
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Forsythiae Fructus (FF), the dried fruit of Forsythia suspensa, has been widely used as a heat-clearing and detoxifying herbal medicine in China. Green FF (GF) and ripe FF (RF) are fruits of Forsythia suspensa at different maturity stages collected about a month apart. FF undergoes a complex series of physical and biochemical changes during fruit ripening. However, the clinical uses of GF and RF have not been distinguished to date. In order to comprehensively compare the chemical compositions of GF and RF, NMR-based metabolomics coupled with HPLC and UV spectrophotometry methods were adopted in this study. Furthermore, the in vitro antioxidant and antibacterial activities of 50% methanol extracts of GF and RF were also evaluated. A total of 27 metabolites were identified based on NMR data, and eight of them were found to be different between the GF and RF groups. The GF group contained higher levels of forsythoside A, forsythoside C, cornoside, rutin, phillyrin and gallic acid and lower levels of rengyol and β-glucose compared with the RF group. The antioxidant activity of GF was higher than that of RF, but no significant difference was observed between the antibacterial activities of GF and RF. Given our results showing their distinct chemical compositions, we propose that NMR-based metabolic profiling can be used to discriminate between GF and RF. Differences in the chemical and biological activities of GF and RF, as well as their clinical efficacies in traditional Chinese medicine should be systematically investigated in future studies. Full article
(This article belongs to the Special Issue Applications of Metabolomics within Natural Products Chemistry)
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Open AccessArticle PLS-Prediction and Confirmation of Hydrojuglone Glucoside as the Antitrypanosomal Constituent of Juglans Spp.
Molecules 2015, 20(6), 10082-10094; doi:10.3390/molecules200610082
Received: 27 April 2015 / Revised: 26 May 2015 / Accepted: 27 May 2015 / Published: 29 May 2015
Cited by 6 | PDF Full-text (1112 KB) | HTML Full-text | XML Full-text
Abstract
Naphthoquinones (NQs) occur naturally in a large variety of plants. Several NQs are highly active against protozoans, amongst them the causative pathogens of neglected tropical diseases such as human African trypanosomiasis (sleeping sickness), Chagas disease and leishmaniasis. Prominent NQ-producing plants can be found
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Naphthoquinones (NQs) occur naturally in a large variety of plants. Several NQs are highly active against protozoans, amongst them the causative pathogens of neglected tropical diseases such as human African trypanosomiasis (sleeping sickness), Chagas disease and leishmaniasis. Prominent NQ-producing plants can be found among Juglans spp. (Juglandaceae) with juglone derivatives as known constituents. In this study, 36 highly variable extracts were prepared from different plant parts of J. regia, J. cinerea and J. nigra. For all extracts, antiprotozoal activity was determined against the protozoans Trypanosoma cruzi, T. brucei rhodesiense and Leishmania donovani. In addition, an LC-MS fingerprint was recorded for each extract. With each extract’s fingerprint and the data on in vitro growth inhibitory activity against T. brucei rhodesiense a Partial Least Squares (PLS) regression model was calculated in order to obtain an indication of compounds responsible for the differences in bioactivity between the 36 extracts. By means of PLS, hydrojuglone glucoside was predicted as an active compound against T. brucei and consequently isolated and tested in vitro. In fact, the pure compound showed activity against T. brucei at a significantly lower cytotoxicity towards mammalian cells than established antiprotozoal NQs such as lapachol. Full article
Open AccessArticle Synthesis and Biological Evaluation of 2-Picolylamide-Based Diselenides with Non-Bonded Interactions
Molecules 2015, 20(6), 10095-10109; doi:10.3390/molecules200610095
Received: 30 April 2015 / Revised: 23 May 2015 / Accepted: 27 May 2015 / Published: 1 June 2015
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Abstract
In this paper, we report the synthesis and biological evaluation of picolylamide-based diselenides with the aim of developing a new series of diselenides with O···Se non-bonded interactions. The synthesis of diselenides was performed by a simple and efficient synthetic route. All
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In this paper, we report the synthesis and biological evaluation of picolylamide-based diselenides with the aim of developing a new series of diselenides with O···Se non-bonded interactions. The synthesis of diselenides was performed by a simple and efficient synthetic route. All the products were obtained in good yields and their structures were determined by 1H-NMR, 13C-NMR and HRMS. All these new compounds showed promising activities when tested in different antioxidant assays. These amides exhibited strong thiol peroxidase-like (TPx) activity. In fact one of the compounds showed 4.66 times higher potential than the classical standard i.e., diphenyl diselenide. The same compound significantly inhibited iron (Fe)-induced thiobarbituric acid reactive species (TBARS) production in rat’s brain homogenate. In addition, the X-ray structure of the most active compound showed non-bonded interaction between the selenium and the oxygen atom that are in close proximity and may be responsible for the increased antioxidant activity. The present study provides evidence about the possible biochemical influence of nonbonding interactions on organochalcogens potency. Full article
(This article belongs to the Special Issue Selenium Catalysts and Antioxidants)
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Open AccessArticle Application of the Cre/loxP Site-Specific Recombination System for Gene Transformation in Aurantiochytrium limacinum
Molecules 2015, 20(6), 10110-10121; doi:10.3390/molecules200610110
Received: 10 April 2015 / Revised: 8 May 2015 / Accepted: 21 May 2015 / Published: 1 June 2015
Cited by 1 | PDF Full-text (2503 KB) | HTML Full-text | XML Full-text
Abstract
The Cre/loxP site-specific recombination system was applied to Aurantiochytrium limacinum to obtain a transformant without the antibiotic resistance marker gene. First, the enhanced green fluorescent protein gene (egfp) and chloramphenicol resistance gene (Cmr), along with the
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The Cre/loxP site-specific recombination system was applied to Aurantiochytrium limacinum to obtain a transformant without the antibiotic resistance marker gene. First, the enhanced green fluorescent protein gene (egfp) and chloramphenicol resistance gene (Cmr), along with the two loxP loci, were integrated into the genome of A. limacinum OUC88 using 18S rDNA sequences as the homologous recombination sites. Then plasmid pSH65, containing a zeocin resistance gene (Bler) was transferred into A. limacinum OUC_CG. After induction with galactose, repeated passage in culture and PCR-based assessment, the pSH65 plasmid was lost and A. limacinum OUC_EG host was shown to no longer have resistance to 100 mg chloramphenicol/L or 5 mg zeocin/L. Through southern blotting and fluorescence detection, egfp was found to be integrated into the genome of A. limacinum OUC_EG, and EGFP was successfully expressed in the cells. The successful application of the Cre/loxP system demonstrates an experimental basis for genetic modification of A. limacinum so as to obtain transformed strains with no antibiotic resistance marker genes. Full article
(This article belongs to the Section Molecular Diversity)
Open AccessCommunication Chlorination of (Phebox)Ir(mesityl)(OAc) by Thionyl Chloride
Molecules 2015, 20(6), 10122-10130; doi:10.3390/molecules200610122
Received: 14 May 2015 / Accepted: 29 May 2015 / Published: 1 June 2015
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Abstract
Pincer (Phebox)Ir(mesityl)(OAc) (2) (Phebox = 3,5-dimethylphenyl-2,6-bis(oxazolinyl)) complex, formed by benzylic C-H activation of mesitylene (1,3,5-trimethylbenzene) using (Phebox)Ir(OAc)2OH2 (1), was treated with thionyl chloride to rapidly form 1-(chloromethyl)-3,5-dimethylbenzene in 50% yield at 23 °C. A green species
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Pincer (Phebox)Ir(mesityl)(OAc) (2) (Phebox = 3,5-dimethylphenyl-2,6-bis(oxazolinyl)) complex, formed by benzylic C-H activation of mesitylene (1,3,5-trimethylbenzene) using (Phebox)Ir(OAc)2OH2 (1), was treated with thionyl chloride to rapidly form 1-(chloromethyl)-3,5-dimethylbenzene in 50% yield at 23 °C. A green species was obtained at the end of reaction, which decomposed during flash column chromatography to form (Phebox)IrCl2OH2 in 87% yield. Full article
(This article belongs to the Special Issue C-H Bond Activation and Functionalization)
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Open AccessCommunication An Alternative Method for Generating Arynes from ortho-Silylaryl Triflates: Activation by Cesium Carbonate in the Presence of a Crown Ether
Molecules 2015, 20(6), 10131-10140; doi:10.3390/molecules200610131
Received: 1 May 2015 / Accepted: 28 May 2015 / Published: 1 June 2015
Cited by 20 | PDF Full-text (1213 KB) | HTML Full-text | XML Full-text
Abstract
An alternative method for generating arynes from ortho-silylaryl triflates using cesium carbonate and 18-crown-6 is reported. The method was efficiently applied to a variety of reactions between several arynes and arynophiles. We also demonstrated that the efficiency of aryne generation is significantly
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An alternative method for generating arynes from ortho-silylaryl triflates using cesium carbonate and 18-crown-6 is reported. The method was efficiently applied to a variety of reactions between several arynes and arynophiles. We also demonstrated that the efficiency of aryne generation is significantly affected by the alkali metal countercation of the carbonate. Full article
(This article belongs to the Special Issue Development and Application of Aryne Chemistry in Organic Synthesis)
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Open AccessArticle Isolation of an Angiotensin I-Converting Enzyme Inhibitory Protein with Antihypertensive Effect in Spontaneously Hypertensive Rats from the Edible Wild Mushroom Leucopaxillus tricolor
Molecules 2015, 20(6), 10141-10153; doi:10.3390/molecules200610141
Received: 5 May 2015 / Accepted: 28 May 2015 / Published: 1 June 2015
Cited by 3 | PDF Full-text (967 KB) | HTML Full-text | XML Full-text
Abstract
An 86-kDa homodimeric angiotensin I-converting enzyme (ACE) inhibitory protein designated as LTP was isolated from fruit bodies of the mushroom Leucopaxillus tricolor. The isolation procedure involved ultrafiltration through a membrane with a molecular weight cutoff of 10-kDa, ion exchange chromatography on Q-Sepharose,
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An 86-kDa homodimeric angiotensin I-converting enzyme (ACE) inhibitory protein designated as LTP was isolated from fruit bodies of the mushroom Leucopaxillus tricolor. The isolation procedure involved ultrafiltration through a membrane with a molecular weight cutoff of 10-kDa, ion exchange chromatography on Q-Sepharose, and finally fast protein liquid chromatography-gel filtration on Superdex 75. LTP exhibited an IC50 value of 1.64 mg∙mL−1 for its ACE inhibitory activity. The unique N-terminal amino acid sequence of LTP was disclosed by Edman degradation to be DGPTMHRQAVADFKQ. In addition, seven internal sequences of LTP were elucidated by liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. Results of the Lineweaver-Burk plot suggested that LTP competitively inhibited ACE. Both LTP and the water extract of L. tricolor exhibited a clear antihypertensive effect on spontaneously hypertensive rats. Full article
(This article belongs to the collection Bioactive Compounds)
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Open AccessArticle Solving Molecular Docking Problems with Multi-Objective Metaheuristics
Molecules 2015, 20(6), 10154-10183; doi:10.3390/molecules200610154
Received: 30 March 2015 / Accepted: 21 May 2015 / Published: 2 June 2015
Cited by 6 | PDF Full-text (3354 KB) | HTML Full-text | XML Full-text
Abstract
Molecular docking is a hard optimization problem that has been tackled in the past with metaheuristics, demonstrating new and challenging results when looking for one objective: the minimum binding energy. However, only a few papers can be found in the literature that deal
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Molecular docking is a hard optimization problem that has been tackled in the past with metaheuristics, demonstrating new and challenging results when looking for one objective: the minimum binding energy. However, only a few papers can be found in the literature that deal with this problem by means of a multi-objective approach, and no experimental comparisons have been made in order to clarify which of them has the best overall performance. In this paper, we use and compare, for the first time, a set of representative multi-objective optimization algorithms applied to solve complex molecular docking problems. The approach followed is focused on optimizing the intermolecular and intramolecular energies as two main objectives to minimize. Specifically, these algorithms are: two variants of the non-dominated sorting genetic algorithm II (NSGA-II), speed modulation multi-objective particle swarm optimization (SMPSO), third evolution step of generalized differential evolution (GDE3), multi-objective evolutionary algorithm based on decomposition (MOEA/D) and S-metric evolutionary multi-objective optimization (SMS-EMOA). We assess the performance of the algorithms by applying quality indicators intended to measure convergence and the diversity of the generated Pareto front approximations. We carry out a comparison with another reference mono-objective algorithm in the problem domain (Lamarckian genetic algorithm (LGA) provided by the AutoDock tool). Furthermore, the ligand binding site and molecular interactions of computed solutions are analyzed, showing promising results for the multi-objective approaches. In addition, a case study of application for aeroplysinin-1 is performed, showing the effectiveness of our multi-objective approach in drug discovery. Full article
(This article belongs to the Special Issue Molecular Docking in Drug Design)
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Open AccessCommunication A New and Efficient Synthesis of 6-O-Methylscutellarein, the Major Metabolite of the Natural Medicine Scutellarin
Molecules 2015, 20(6), 10184-10191; doi:10.3390/molecules200610184
Received: 23 April 2015 / Revised: 28 May 2015 / Accepted: 29 May 2015 / Published: 2 June 2015
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Abstract
In this paper, a new and efficient synthesis of 6-O-methylscutellarein (3), the major metabolite of the natural medicine scutellarin, is reported. Two hydroxyl groups at C-4′ and C-7 in 2 were selectively protected by chloromethyl methyl ether after the
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In this paper, a new and efficient synthesis of 6-O-methylscutellarein (3), the major metabolite of the natural medicine scutellarin, is reported. Two hydroxyl groups at C-4′ and C-7 in 2 were selectively protected by chloromethyl methyl ether after the reaction conditions were optimized, then 6-O-methyl-scutellarein (3) was produced in high yield after methylation of the hydroxyl group at C-6 and subsequent deprotection of the two methyl ether groups. Full article
(This article belongs to the Section Organic Synthesis)
Open AccessCommunication Synthesis of a Novel Cysteine-Incorporated Anthraquinone Derivative and Its Structural Properties
Molecules 2015, 20(6), 10192-10204; doi:10.3390/molecules200610192
Received: 6 March 2015 / Accepted: 22 May 2015 / Published: 3 June 2015
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Abstract
A novel cysteine-incorporated anthraquinone derivative was synthesized, and its molecular structure was determined by X-ray crystal analysis. Each mercapto group was located separately and did not form a disulfide bond, and hydrogen bondings and π-π interaction were observed from the packing structure. Full article
(This article belongs to the Section Organic Synthesis)
Open AccessArticle Effect of Methoxy Substituents on the Activation Barriers of the Glutathione Peroxidase-Like Mechanism of an Aromatic Cyclic Seleninate
Molecules 2015, 20(6), 10244-10252; doi:10.3390/molecules200610244
Received: 12 May 2015 / Revised: 26 May 2015 / Accepted: 1 June 2015 / Published: 3 June 2015
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Abstract
Density functional theory (DFT) models including explicit water molecules have been used to model the redox scavenging mechanism of aromatic cyclic seleninates. Experimental studies have shown that methoxy substitutions affect the rate of scavenging of reactive oxygen species differently depending upon the position.
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Density functional theory (DFT) models including explicit water molecules have been used to model the redox scavenging mechanism of aromatic cyclic seleninates. Experimental studies have shown that methoxy substitutions affect the rate of scavenging of reactive oxygen species differently depending upon the position. Activities are enhanced in the para position, unaffected in the meta, and decreased in the ortho. DFT calculations show that the activation barrier for the oxidation of the selenenyl sulfide, a proposed key intermediate, is higher for the ortho methoxy derivative than for other positions, consistent with the low experimental conversion rate. Full article
(This article belongs to the Special Issue Selenium Catalysts and Antioxidants)
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Open AccessCommunication Synthesis of Phospholipid-Protein Conjugates as New Antigens for Autoimmune Antibodies
Molecules 2015, 20(6), 10253-10263; doi:10.3390/molecules200610253
Received: 10 April 2015 / Revised: 27 May 2015 / Accepted: 28 May 2015 / Published: 3 June 2015
Cited by 3 | PDF Full-text (967 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Copper(I)-catalyzed azide-alkyne cycloaddition, or CuAAC click chemistry, is an efficient method for bioconjugation aiming at chemical and biological applications. Herein, we demonstrate how the CuAAC method can provide novel phospholipid-protein conjugates with a high potential for the diagnostics and therapy of autoimmune conditions.
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Copper(I)-catalyzed azide-alkyne cycloaddition, or CuAAC click chemistry, is an efficient method for bioconjugation aiming at chemical and biological applications. Herein, we demonstrate how the CuAAC method can provide novel phospholipid-protein conjugates with a high potential for the diagnostics and therapy of autoimmune conditions. In doing this, we, for the first time, covalently bind via 1,2,3-triazole linker biologically complementary molecules, namely phosphoethanol amine with human β2-glycoprotein I and prothrombin. The resulting phospholipid-protein conjugates show high binding affinity and specificity for the autoimmune antibodies against autoimmune complexes. Thus, the development of this work might become a milestone in further diagnostics and therapy of autoimmune diseases that involve the production of autoantibodies against the aforementioned phospholipids and proteins, such as antiphospholipid syndrome and systemic lupus erythematosus. Full article
(This article belongs to the Special Issue Advances in Click Chemistry)
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Open AccessArticle Sevoflurane-Sulfobutylether-β-Cyclodextrin Complex: Preparation, Characterization, Cellular Toxicity, Molecular Modeling and Blood-Brain Barrier Transport Studies
Molecules 2015, 20(6), 10264-10279; doi:10.3390/molecules200610264
Received: 12 April 2015 / Accepted: 25 May 2015 / Published: 3 June 2015
Cited by 9 | PDF Full-text (5530 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The objective of the present investigation was to study the ability of sulfobutylether-β-cyclodextrin (SBEβCD) to form an inclusion complex with sevoflurane (SEV), a volatile anesthetic with poor water solubility. The inclusion complex was prepared, characterized and its cellular toxicity and blood-brain barrier (BBB)
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The objective of the present investigation was to study the ability of sulfobutylether-β-cyclodextrin (SBEβCD) to form an inclusion complex with sevoflurane (SEV), a volatile anesthetic with poor water solubility. The inclusion complex was prepared, characterized and its cellular toxicity and blood-brain barrier (BBB) permeation potential of the formulated SEV have also been examined for the purpose of controlled drug delivery. The SEV-SBEβCD complex was nontoxic to the primary brain microvascular endothelial (pEND) cells at a clinically relevant concentration of sevoflurane. The inclusion complex exhibited significantly higher BBB permeation profiles as compared with the reference substance (propranolol) concerning calculated apparent permeability values (Papp). In addition, SEV binding affinity to SBEβCD was confirmed by a minimal Gibbs free energy of binding (ΔGbind) value of −1.727 ± 0.042 kcal·mol−1 and an average binding constant (Kb) of 53.66 ± 9.24 mM indicating rapid drug liberation from the cyclodextrin amphiphilic cavity. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle γ-Tocotrienol and 6-Gingerol in Combination Synergistically Induce Cytotoxicity and Apoptosis in HT-29 and SW837 Human Colorectal Cancer Cells
Molecules 2015, 20(6), 10280-10297; doi:10.3390/molecules200610280
Received: 4 May 2015 / Revised: 27 May 2015 / Accepted: 28 May 2015 / Published: 3 June 2015
Cited by 3 | PDF Full-text (2726 KB) | HTML Full-text | XML Full-text
Abstract
Numerous bioactive compounds have cytotoxic properties towards cancer cells. However, most studies have used single compounds when bioactives may target different pathways and exert greater cytotoxic effects when used in combination. Therefore, the objective of this study was to determine the anti-proliferative effect
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Numerous bioactive compounds have cytotoxic properties towards cancer cells. However, most studies have used single compounds when bioactives may target different pathways and exert greater cytotoxic effects when used in combination. Therefore, the objective of this study was to determine the anti-proliferative effect of γ-tocotrienol (γ-T3) and 6-gingerol (6G) in combination by evaluating apoptosis and active caspase-3 in HT-29 and SW837 colorectal cancer cells. MTS assays were performed to determine the anti-proliferative and cytotoxicity effect of γ-T3 (0–150 µg/mL) and 6G (0–300 µg/mL) on the cells. The half maximal inhibitory concentration (IC50) value of 6G+ γ-T3 for HT-29 was 105 + 67 µg/mL and for SW837 it was 70 + 20 µg/mL. Apoptosis, active caspase-3 and annexin V FITC assays were performed after 24 h of treatment using flow cytometry. These bioactives in combination showed synergistic effect on HT-29 (CI: 0.89 ± 0.02,) and SW837 (CI: 0.79 ± 0.10) apoptosis was increased by 21.2% in HT-29 and 55.4% in SW837 (p < 0.05) after 24 h treatment, while normal hepatic WRL-68 cells were unaffected. Increased apoptosis by the combined treatments was also observed morphologically, with effects like cell shrinkage and pyknosis. In conclusion, although further studies need to be done, γ-T3 and 6G when used in combination act synergistically increasing cytotoxicity and apoptosis in cancer cells. Full article
(This article belongs to the collection Bioactive Compounds)
Open AccessArticle An Effective Quality Control of Pharmacologically Active Volatiles of Houttuynia cordata Thunb by Fast Gas Chromatography-Surface Acoustic Wave Sensor
Molecules 2015, 20(6), 10298-10312; doi:10.3390/molecules200610298
Received: 31 March 2015 / Accepted: 19 May 2015 / Published: 3 June 2015
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Abstract
Fast gas chromatography-surface acoustic wave sensor (GC/SAW) has been applied for the detection of the pharmacological volatiles emanated from Houttuynia cordata Thunb which is from South Korea. H. cordata Thunb with unpleasant and fishy odors shows a variety of pharmacological activities such as
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Fast gas chromatography-surface acoustic wave sensor (GC/SAW) has been applied for the detection of the pharmacological volatiles emanated from Houttuynia cordata Thunb which is from South Korea. H. cordata Thunb with unpleasant and fishy odors shows a variety of pharmacological activities such as anti-microbial, anti-inflammatory, anti-cancer, and insect repellent. The aim of this study is to show a novel quality control by GC/SAW methodology for the discrimination of the three different parts of the plant such as leaves, aerial stems, and underground stems for H. cordata Thunb. Sixteen compounds were identified. β-Myrcene, cis-ocimene and decanal are the dominant volatiles for leaves (71.0%) and aerial stems (50.1%). While, monoterpenes (74.6%) are the dominant volatiles for underground stems. 2-Undecanone (1.3%) and lauraldehyde (3.5%) were found to be the characteristic components for leaves. Each part of the plant has its own characteristic fragrance pattern owing to its individual chemical compositions. Moreover, its individual characteristic fragrance patterns are conducive to discrimination of the three different parts of the plant. Consequently, fast GC/SAW can be a useful analytical method for quality control of the different parts of the plant with pharmacological volatiles as it provides second unit analysis, a simple and fragrant pattern recognition. Full article
(This article belongs to the collection Recent Advances in Flavors and Fragrances)
Open AccessArticle Discovery of Novel Small Molecule Anti-HCV Agents via the CypA Inhibitory Mechanism Using O-Acylation-Directed Lead Optimization
Molecules 2015, 20(6), 10342-10359; doi:10.3390/molecules200610342
Received: 6 May 2015 / Revised: 28 May 2015 / Accepted: 29 May 2015 / Published: 4 June 2015
PDF Full-text (871 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In this work, the relationship between cyclophilin A (CypA) and HCV prompted us to screen a series of small molecule CypA inhibitors which were previously reported by our group. Among them, compound 1, discovered as a non-immunosuppressive anti-HCV agent with an EC
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In this work, the relationship between cyclophilin A (CypA) and HCV prompted us to screen a series of small molecule CypA inhibitors which were previously reported by our group. Among them, compound 1, discovered as a non-immunosuppressive anti-HCV agent with an EC50 value of 0.67 μM in a virus assay, was selected for further study. Subsequent chemical modification by O-acylation led to a novel class of molecules, among which compound 25 demonstrated the most potent anti-HCV activity in the virus assay (EC50 = 0.19 μM), but low cytotoxicity and hERG cardiac toxicity. The following studies (a solution stability assay and a simple pharmacokinetic test together with a CypA enzyme inhibition assay) preliminarily indicated that 25 was a prodrug of 1. To the best of our knowledge, 25 is probably the most potent currently reported small molecule anti-HCV agent acting via the CypA inhibitory mechanism. Consequently, our study has provided a new potential small molecule for curing HCV infection. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Biological Activity and Molecular Structures of Bis(benzimidazole) and Trithiocyanurate Complexes
Molecules 2015, 20(6), 10360-10376; doi:10.3390/molecules200610360
Received: 31 March 2015 / Revised: 22 May 2015 / Accepted: 29 May 2015 / Published: 4 June 2015
Cited by 8 | PDF Full-text (1287 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
1-(1H-Benzimidazol-2-yl)-N-(1H-benzimidazol-2-ylmethyl)methanamine (abb) and 2-(1H-benzimidazol-2-ylmethylsulfanylmethyl)-1H-benzimidazole (tbb) have been prepared and characterized by elemental analysis. These bis(benzimidazoles) have been further used in combination with trithiocyanuric acid for the preparation of complexes.
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1-(1H-Benzimidazol-2-yl)-N-(1H-benzimidazol-2-ylmethyl)methanamine (abb) and 2-(1H-benzimidazol-2-ylmethylsulfanylmethyl)-1H-benzimidazole (tbb) have been prepared and characterized by elemental analysis. These bis(benzimidazoles) have been further used in combination with trithiocyanuric acid for the preparation of complexes. The crystal and molecular structures of two of them have been solved. Each nickel atom in the structure of trinuclear complex [Ni3(abb)3(H2O)3(μ-ttc)](ClO4)3·3H2O·EtOH (1), where ttcH3 = trithiocyanuric acid, is coordinated with three N atoms of abb, the N,S donor set of ttc anion and an oxygen of a water molecule. The crystal of [(tbbH2)(ttcH2)2(ttcH3)(H2O)] (2) is composed of a protonated bis(benzimidazole), two ttcH2 anions, ttcH3 and water. The structure is stabilized by a network of hydrogen bonds. These compounds were primarily synthesized for their potential antimicrobial activity and hence their possible use in the treatment of infections caused by bacteria or yeasts (fungi). The antimicrobial and antifungal activity of the prepared compounds have been evaluated on a wide spectrum of bacterial and yeast strains and clinical specimens isolated from patients with infectious wounds and the best antimicrobial properties were observed in strains after the use of ligand abb and complex 1, when at least 80% growth inhibition was achieved. Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessArticle Glutathione Levels and Susceptibility to Chemically Induced Injury in Two Human Prostate Cancer Cell Lines
Molecules 2015, 20(6), 10399-10414; doi:10.3390/molecules200610399
Received: 17 February 2015 / Revised: 27 May 2015 / Accepted: 1 June 2015 / Published: 5 June 2015
Cited by 2 | PDF Full-text (4146 KB) | HTML Full-text | XML Full-text
Abstract
More aggressive prostate cancer cells (PCCs) are often resistant to chemotherapy. Differences exist in redox status and mitochondrial metabolism that may help explain this phenomenon. Two human PCC lines, PC-3 cells (more aggressive) and LNCaP cells (less aggressive), were compared with regard to
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More aggressive prostate cancer cells (PCCs) are often resistant to chemotherapy. Differences exist in redox status and mitochondrial metabolism that may help explain this phenomenon. Two human PCC lines, PC-3 cells (more aggressive) and LNCaP cells (less aggressive), were compared with regard to cellular glutathione (GSH) levels, susceptibility to either oxidants or GSH depletors, and expression of several proteins involved in apoptosis and stress response to test the hypothesis that more aggressive PCCs exhibit higher GSH concentrations and are relatively resistant to cytotoxicity. PC-3 cells exhibited 4.2-fold higher GSH concentration than LNCaP cells but only modest differences in acute cytotoxicity were observed at certain time points. However, only LNCaP cells underwent diamide-induced apoptosis. PC-3 cells exhibited higher levels of Bax and caspase-8 cleavage product but lower levels of Bcl-2 than LNCaP cells. However, LNCaP cells exhibited higher expression of Fas receptor (FasR) but also higher levels of several stress response and antioxidant proteins than PC-3 cells. LNCaP cells also exhibited higher levels of several mitochondrial antioxidant systems, suggesting a compensatory response. Thus, significant differences in redox status and expression of proteins involved in apoptosis and stress response may contribute to PCC aggressiveness. Full article
(This article belongs to the Special Issue Thioredoxin and Glutathione Systems)
Open AccessArticle Molecular Characterisation of the Haemagglutinin Glycan-Binding Specificity of Egg-Adapted Vaccine Strains of the Pandemic 2009 H1N1 Swine Influenza A Virus
Molecules 2015, 20(6), 10415-10434; doi:10.3390/molecules200610415
Received: 13 May 2015 / Accepted: 1 June 2015 / Published: 5 June 2015
Cited by 2 | PDF Full-text (3553 KB) | HTML Full-text | XML Full-text
Abstract
The haemagglutinin (HA) glycan binding selectivity of H1N1 influenza viruses is an important determinant for the host range of the virus and egg-adaption during vaccine production. This study integrates glycan binding data with structure-recognition models to examine the impact of the K123N, D225G
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The haemagglutinin (HA) glycan binding selectivity of H1N1 influenza viruses is an important determinant for the host range of the virus and egg-adaption during vaccine production. This study integrates glycan binding data with structure-recognition models to examine the impact of the K123N, D225G and Q226R mutations (as seen in the HA of vaccine strains of the pandemic 2009 H1N1 swine influenza A virus). The glycan-binding selectivity of three A/California/07/09 vaccine production strains, and purified recombinant A/California/07/09 HAs harboring these mutations was examined via a solid-phase ELISA assay. Wild-type A/California/07/09 recombinant HA bound specifically to α2,6-linked sialyl-glycans, with no affinity for the α2,3-linked sialyl-glycans in the array. In contrast, the vaccine virus strains and recombinant HA harboring the Q226R HA mutation displayed a comparable pattern of highly specific binding to α2,3-linked sialyl-glycans, with a negligible affinity for α2,6-linked sialyl-glycans. The D225G A/California/07/09 recombinant HA displayed an enhanced binding affinity for both α2,6- and α2,3-linked sialyl-glycans in the array. Notably its α2,6-glycan affinity was generally higher compared to its α2,3-glycan affinity, which may explain why the double mutant was not naturally selected during egg-adaption of the virus. The K123N mutation which introduces a glycosylation site proximal to the receptor binding site, did not impact the α2,3/α2,6 glycan selectivity, however, it lowered the overall glycan binding affinity of the HA; suggesting glycosylation may interfere with receptor binding. Docking models and ‘per residues’ scoring were employed to provide a structure-recognition rational for the experimental glycan binding data. Collectively, the glycan binding data inform future vaccine design strategies to introduce the D225G or Q226R amino acid substitutions into recombinant H1N1 viruses. Full article
(This article belongs to the Special Issue Protein-Carbohydrate Interactions, and Beyond)
Open AccessArticle KMUP-1 Attenuates Endothelin-1-Induced Cardiomyocyte Hypertrophy through Activation of Heme Oxygenase-1 and Suppression of the Akt/GSK-3β, Calcineurin/NFATc4 and RhoA/ROCK Pathways
Molecules 2015, 20(6), 10435-10449; doi:10.3390/molecules200610435
Received: 19 March 2015 / Revised: 2 June 2015 / Accepted: 2 June 2015 / Published: 5 June 2015
Cited by 6 | PDF Full-text (3101 KB) | HTML Full-text | XML Full-text
Abstract
The signaling cascades of the mitogen activated protein kinase (MAPK) family, calcineurin/NFATc4, and PI3K/Akt/GSK3, are believed to participate in endothelin-1 (ET-1)-induced cardiac hypertrophy. The aim of this study was to investigate whether KMUP-1, a synthetic xanthine-based derivative, prevents cardiomyocyte hypertrophy induced by ET-1
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The signaling cascades of the mitogen activated protein kinase (MAPK) family, calcineurin/NFATc4, and PI3K/Akt/GSK3, are believed to participate in endothelin-1 (ET-1)-induced cardiac hypertrophy. The aim of this study was to investigate whether KMUP-1, a synthetic xanthine-based derivative, prevents cardiomyocyte hypertrophy induced by ET-1 and to elucidate the underlying mechanisms. We found that in H9c2 cardiomyocytes, stimulation with ET-1 (100 nM) for 4 days induced cell hypertrophy and enhanced expressions of hypertrophic markers, including atrial natriuretic peptide and brain natriuretic peptide, which were all inhibited by KMUP-1 in a dose-dependent manner. In addition, KMUP-1 prevented ET-1-induced intracellular reactive oxygen species generation determined by the DCFH-DA assay in cardiomyocytes. KMUP-1 also attenuated phosphorylation of ERK1/2 and Akt/GSK-3β, and activation of calcineurin/NFATc4 and RhoA/ROCK pathways induced by ET-1. Furthermore, we found that the expression of heme oxygenase-1 (HO-1), a stress-response enzyme implicated in cardio-protection, was up-regulated by KMUP-1. Finally, KMUP-1 attenuated ET-1-stimulated activator protein-1 DNA binding activity. In conclusion, KMUP-1 attenuates cardiomyocyte hypertrophy induced by ET-1 through inhibiting ERK1/2, calcineurin/NFATc4 and RhoA/ROCK pathways, with associated cardioprotective effects via HO-1 activation. Therefore, KMUP-1 may have a role in pharmacological therapy of cardiac hypertrophy. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Optimization of Purification, Identification and Evaluation of the in Vitro Antitumor Activity of Polyphenols from Pinus Koraiensis Pinecones
Molecules 2015, 20(6), 10450-10467; doi:10.3390/molecules200610450
Received: 6 February 2015 / Revised: 12 May 2015 / Accepted: 2 June 2015 / Published: 5 June 2015
Cited by 8 | PDF Full-text (982 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In this study, an efficient purification method for the polyphenols of Pinus koraiensis pinecone (PPP) has been developed. AB-8 resin was verified to offer good adsorption and desorption ratio for PPP. Response surface methodology (RSM) indicated that the optimized purification parameters for PPP
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In this study, an efficient purification method for the polyphenols of Pinus koraiensis pinecone (PPP) has been developed. AB-8 resin was verified to offer good adsorption and desorption ratio for PPP. Response surface methodology (RSM) indicated that the optimized purification parameters for PPP were 1.70 mg GAE/mL phenolic sample concentration, 22.00 mL sample volume, and 63.00% ethanol concentration. Under these conditions, the experimental purity of PPP was 27.93 ± 0.14% (n = 3), which matched well with the predicted purity of 28.17%. Next, the antiproliferative effects of PPP on seven cancer cell lines, including A375 (human skin melanoma cancer cell line), A549 (human lung cancer cell line), SH-SY5Y (human neuroblastoma cell line), LOVO (human colon cancer stem cell line), MCF-7 (human breast cancer cell line), HeLa (human cervical cancer line), and HT29 (human colon cancer line), were examined by MTT assays. The results indicated that PPP had the highest capacity for inhibiting LOVO cells growth with an EC50 value of 0.317 ± 0.0476 mg/mL. Finally, Ultra-high performance liquid chromatography- tandem mass spectrometry (UPLC-MS) was used to tentatively identify twenty-four peaks in the purified PPP, of which five representative peaks were identified as catechin, methyl quercetin, o-vanillin, luteolin and coronaric acid. Our results demonstrate that Pinus koraiensis pinecone is a readily available source of polyphenols, and the purified PPP could be a promising natural antitumor agent for applications in functional foods. Full article
Open AccessArticle Synthesis, Characterization, Antimicrobial Screening and Free-Radical Scavenging Activity of Some Novel Substituted Pyrazoles
Molecules 2015, 20(6), 10468-10486; doi:10.3390/molecules200610468
Received: 26 April 2015 / Revised: 1 June 2015 / Accepted: 1 June 2015 / Published: 8 June 2015
Cited by 5 | PDF Full-text (771 KB) | HTML Full-text | XML Full-text
Abstract
The present work deals with the synthesis of acetoxysulfonamide pyrazole derivatives, substituted 4,5-dihydropyrazole-1-carbothioamide and 4,5-dihydropyrazole-1-isonicotinoyl derivatives starting from substituted vanillin chalcones. Acetoxysulfonamide pyrazole derivatives were prepared from the reaction of chalcones with p-sulfamylphenylhydrazine followed by treatment with acetic anhydride. At the same
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The present work deals with the synthesis of acetoxysulfonamide pyrazole derivatives, substituted 4,5-dihydropyrazole-1-carbothioamide and 4,5-dihydropyrazole-1-isonicotinoyl derivatives starting from substituted vanillin chalcones. Acetoxysulfonamide pyrazole derivatives were prepared from the reaction of chalcones with p-sulfamylphenylhydrazine followed by treatment with acetic anhydride. At the same time 4,5-dihydropyrazole-1-carbothioamide and 4,5-dihydropyrazole-1-isonicotinoyl derivatives were prepared from the reaction of chalcones with either thiosemicarbazide or isonicotinic acid hydrazide, respectively. The synthesized compounds were structurally characterized on the basis of IR, 1H-NMR, 13C-NMR spectral data and microanalyses. All of the newly isolated compounds were tested for their antimicrobial activities. The antimicrobial screening using the agar well-diffusion method revealed that the chloro derivatives are the most active ones. Moreover, the antioxidant and anti-inflammatory activity of these chloro derivatives are also studied using the DPPH radical scavenging and NO radical scavenging methods, respectively. Full article
(This article belongs to the collection Heterocyclic Compounds)
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Open AccessCommunication Efficient Esterification of Oxidized l-Glutathione and Other Small Peptides
Molecules 2015, 20(6), 10487-10495; doi:10.3390/molecules200610487
Received: 17 May 2015 / Revised: 3 June 2015 / Accepted: 4 June 2015 / Published: 8 June 2015
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Abstract
Oxidized l-glutathione was esterified to the tetra methyl ester using thionyl chloride in methanol solvent. Other alcohols were tested and the reaction progress was monitored via ESI-MS. This procedure proved to be compatible with other small peptides not containing serine and cysteine residues.
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Oxidized l-glutathione was esterified to the tetra methyl ester using thionyl chloride in methanol solvent. Other alcohols were tested and the reaction progress was monitored via ESI-MS. This procedure proved to be compatible with other small peptides not containing serine and cysteine residues. In contrast to previously reported methods this procedure provided convenient access to esterified peptides requiring no purification, extended reaction times, or complicated reaction setups. Full article
(This article belongs to the Section Molecular Diversity)
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Open AccessArticle Selenium Catalyzed Oxidation of Aldehydes: Green Synthesis of Carboxylic Acids and Esters
Molecules 2015, 20(6), 10496-10510; doi:10.3390/molecules200610496
Received: 30 April 2015 / Revised: 27 May 2015 / Accepted: 3 June 2015 / Published: 8 June 2015
Cited by 21 | PDF Full-text (930 KB) | HTML Full-text | XML Full-text
Abstract
The stoichiometric use of hydrogen peroxide in the presence of a selenium-containing catalyst in water is here reported as a new ecofriendly protocol for the synthesis of variously functionalized carboxylic acids and esters. The method affords the desired products in good to excellent
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The stoichiometric use of hydrogen peroxide in the presence of a selenium-containing catalyst in water is here reported as a new ecofriendly protocol for the synthesis of variously functionalized carboxylic acids and esters. The method affords the desired products in good to excellent yields under very mild conditions starting directly from commercially available aldehydes. Using benzaldehyde as a prototype the gram scale synthesis of benzoic acid is described, in which the aqueous medium and the catalyst could be recycled at last five times while achieving an 87% overall yield. Full article
(This article belongs to the Special Issue Selenium Catalysts and Antioxidants)
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Open AccessArticle Effects of Fusarium solani and F. oxysporum Infection on the Metabolism of Ginsenosides in American Ginseng Roots
Molecules 2015, 20(6), 10535-10552; doi:10.3390/molecules200610535
Received: 7 April 2015 / Accepted: 3 June 2015 / Published: 8 June 2015
Cited by 3 | PDF Full-text (1020 KB) | HTML Full-text | XML Full-text
Abstract
American ginseng (Panax quinquefolius L.) is a highly valuable herb widely used for medicinal treatments. Its pharmacologically important compounds are the ginsenosides, which are secondary metabolites in American ginseng root. The concentrations of ginsenoside in roots can be changed by fungal infection,
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American ginseng (Panax quinquefolius L.) is a highly valuable herb widely used for medicinal treatments. Its pharmacologically important compounds are the ginsenosides, which are secondary metabolites in American ginseng root. The concentrations of ginsenoside in roots can be changed by fungal infection, but it is unclear what specific root tissues are impacted and whether the change is systemic. In this study, American ginseng roots were inoculated with two fungal pathogens (Fusarium solani or F. oxysporum) and the levels of six ginsenosides (Rb1, Rb2, Rc, Rd, Re, and Rg1) were then measured in the phloem and xylem around the discolored lesions and adjacent healthy areas of the root. Results indicated that the growth of Fusarium spp. was strictly limited to phloem, and correspondingly the ginsenoside concentration was only altered in this infected phloem. The concentration of Rg1, Rd, and Rc significantly changed in phloem tissues where F. solani was inoculated, while only Rg1 and Rd changed significantly after F. oxysporum inoculation. However, no changes of any ginsenoside occurred in either xylem or phloem tissue adjacent to the inoculation point. In addition, when two Fusarium spp. were grown on ginsenoside-amended Czapek medium, the majority of ginsenosides were depleted. Therefore, pathogenic Fusarium spp. may reduce ginsenoside levels by consuming them. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Analysis of Flavonoids in Lotus (Nelumbo nucifera) Leaves and Their Antioxidant Activity Using Macroporous Resin Chromatography Coupled with LC-MS/MS and Antioxidant Biochemical Assays
Molecules 2015, 20(6), 10553-10565; doi:10.3390/molecules200610553
Received: 27 March 2015 / Accepted: 29 May 2015 / Published: 8 June 2015
Cited by 13 | PDF Full-text (1007 KB) | HTML Full-text | XML Full-text
Abstract
Lotus (Nelumbo nucifera) leaves, a traditional Chinese medicinal herb, are rich in flavonoids. In an effort to thoroughly analyze their flavonoid components, macroporous resin chromatography coupled with HPLC-MS/MS was employed to simultaneously enrich and identify flavonoids from lotus leaves. Flavonoids extracted
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Lotus (Nelumbo nucifera) leaves, a traditional Chinese medicinal herb, are rich in flavonoids. In an effort to thoroughly analyze their flavonoid components, macroporous resin chromatography coupled with HPLC-MS/MS was employed to simultaneously enrich and identify flavonoids from lotus leaves. Flavonoids extracted from lotus leaves were selectively enriched in the macroporous resin column, eluted subsequently as fraction II, and successively subjected to analysis with the HPLC-MS/MS and bioactivity assays. Altogether, fourteen flavonoids were identified, four of which were identified from lotus leaves for the first time, including quercetin 3-O-rhamnopyranosyl-(1→2)-glucopyranoside, quercetin 3-O-arabinoside, diosmetin 7-O-hexose, and isorhamnetin 3-O-arabino- pyranosyl-(1→2)-glucopyranoside. Further bioactivity assays revealed that these flavonoids from lotus leaves possess strong antioxidant activity, and demonstrate very good potential to be explored as food supplements or even pharmaceutical products to improve human health. Full article
(This article belongs to the collection Bioactive Compounds)
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Open AccessArticle Continuous Polyol Synthesis of Metal and Metal Oxide Nanoparticles Using a Segmented Flow Tubular Reactor (SFTR)
Molecules 2015, 20(6), 10566-10581; doi:10.3390/molecules200610566
Received: 12 May 2015 / Revised: 22 May 2015 / Accepted: 26 May 2015 / Published: 8 June 2015
Cited by 5 | PDF Full-text (4824 KB) | HTML Full-text | XML Full-text
Abstract
Over the last years a new type of tubular plug flow reactor, the segmented flow tubular reactor (SFTR), has proven its versatility and robustness through the water-based synthesis of precipitates as varied as CaCO3, BaTiO3, Mn(1−x)Nix
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Over the last years a new type of tubular plug flow reactor, the segmented flow tubular reactor (SFTR), has proven its versatility and robustness through the water-based synthesis of precipitates as varied as CaCO3, BaTiO3, Mn(1−x)NixC2O4·2H2O, YBa oxalates, copper oxalate, ZnS, ZnO, iron oxides, and TiO2 produced with a high powder quality (phase composition, particle size, and shape) and high reproducibility. The SFTR has been developed to overcome the classical problems of powder production scale-up from batch processes, which are mainly linked with mass and heat transfer. Recently, the SFTR concept has been further developed and applied for the synthesis of metals, metal oxides, and salts in form of nano- or micro-particles in organic solvents. This has been done by increasing the working temperature and modifying the particle carrying solvent. In this paper we summarize the experimental results for four materials prepared according to the polyol synthesis route combined with the SFTR. CeO2, Ni, Ag, and Ca3(PO4)2 nanoparticles (NPs) can be obtained with a production rate of about 1–10 g per h. The production was carried out for several hours with constant product quality. These findings further corroborate the reliability and versatility of the SFTR for high throughput powder production. Full article
(This article belongs to the Special Issue Recent Advances in Flow Chemistry)
Open AccessArticle ŸKinetics of the Reaction of Pyrogallol Red, a Polyphenolic Dye, with Nitrous Acid: Role of Ÿ•NO and •NO2
Molecules 2015, 20(6), 10582-10593; doi:10.3390/molecules200610582
Received: 7 April 2015 / Revised: 24 May 2015 / Accepted: 26 May 2015 / Published: 8 June 2015
Cited by 1 | PDF Full-text (853 KB) | HTML Full-text | XML Full-text
Abstract
In the present work we studied the reaction under gastric conditions of pyrogallol red (PGR), a polyphenolic dye, with nitrous acid (HONO). PGR has been used as a model polyphenol due to its strong UV-visible absorption and its high reactivity towards reactive species
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In the present work we studied the reaction under gastric conditions of pyrogallol red (PGR), a polyphenolic dye, with nitrous acid (HONO). PGR has been used as a model polyphenol due to its strong UV-visible absorption and its high reactivity towards reactive species (radicals and non-radicals, RS). The reaction was followed by UV-visible spectroscopy and high performance liquid chromatography (HPLC). A clear decrease of the PGR absorbance at 465 nm was observed, evidencing an efficient bleaching of PGR by HONO. In the initial stages of the reaction, each HONO molecule nearly consumed 2.6 PGR molecules while, at long reaction times, ca. 7.0 dye molecules were consumed per each reacted HONO. This result is interpreted in terms of HONO recycling. During the PGR-HONO reaction, nitric oxide was generated in the micromolar range. In addition, the rate of PGR consumption induced by HONO was almost totally abated by argon bubbling, emphasising the role that critical volatile intermediates, such as ŸNO and/or nitrogen dioxide (ŸNO2), play in the bleaching of this phenolic compound. Full article
(This article belongs to the Section Metabolites)
Open AccessArticle Microwave-Assisted Synthesis of Cinnamyl Long Chain Aroma Esters
Molecules 2015, 20(6), 10594-10603; doi:10.3390/molecules200610594
Received: 4 May 2015 / Revised: 24 May 2015 / Accepted: 1 June 2015 / Published: 8 June 2015
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Abstract
Cinnamyl long chain aroma esters were prepared by using the conventional and microwave-assisted methods. The esterification reaction of naturally occurring 3-phenyl-prop-2-en-1-ol and different chain lengths acidic and diol reagents was carried out at the temperature of 140 °C under solvent free conditions. As
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Cinnamyl long chain aroma esters were prepared by using the conventional and microwave-assisted methods. The esterification reaction of naturally occurring 3-phenyl-prop-2-en-1-ol and different chain lengths acidic and diol reagents was carried out at the temperature of 140 °C under solvent free conditions. As acidic reagents, oxolane-2,5-dione, oxane-2,6-dione, hexanedioic acid and decanedioic acid were applied. Ethane-1,2-diol and 2,2ʹ-[oxybis(2,1-ethandiyloxy)]diethanol were used as diol reagents. The synthesis of high molecular mass cinnamyl esters under conventional method conditions requires a long time to obtain high yields. The studies confirm that by using microwave irradiation, it is possible to reduce the reaction times to only 10–20 min. The structures of prepared esters were confirmed on the basis of FTIR, 1H-NMR and 13C-NMR. In addition, the newly obtained cinnamyl long chain esters were tested for their thermal properties. The TG studies proved the high thermal resistance of the obtained esters under inert and oxidative conditions. Full article
(This article belongs to the collection Recent Advances in Flavors and Fragrances)
Open AccessArticle Antiviral, Antifungal and Antibacterial Activities of a BODIPY-Based Photosensitizer
Molecules 2015, 20(6), 10604-10621; doi:10.3390/molecules200610604
Received: 23 February 2015 / Revised: 30 May 2015 / Accepted: 4 June 2015 / Published: 8 June 2015
Cited by 9 | PDF Full-text (978 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Antimicrobial photodynamic inactivation (aPDI) employing the BODIPY-based photosensitizer 2,6-diiodo-1,3,5,7-tetramethyl-8-(N-methyl-4-pyridyl)-4,4′-difluoro-boradiazaindacene (DIMPy-BODIPY) was explored in an in vitro assay against six species of bacteria (eight total strains), three species of yeast, and three viruses as a complementary approach to their current drug-based or
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Antimicrobial photodynamic inactivation (aPDI) employing the BODIPY-based photosensitizer 2,6-diiodo-1,3,5,7-tetramethyl-8-(N-methyl-4-pyridyl)-4,4′-difluoro-boradiazaindacene (DIMPy-BODIPY) was explored in an in vitro assay against six species of bacteria (eight total strains), three species of yeast, and three viruses as a complementary approach to their current drug-based or non-existent treatments. Our best results achieved a noteworthy 5–6 log unit reduction in CFU at 0.1 μM for Staphylococcus aureus (ATCC-2913), methicillin-resistant S. aureus (ATCC-44), and vancomycin-resistant Enterococcus faecium (ATCC-2320), a 4–5 log unit reduction for Acinetobacter baumannii ATCC-19606 (0.25 μM), multidrug resistant A. baumannii ATCC-1605 (0.1 μM), Pseudomonas aeruginosa ATCC-97 (0.5 μM), and Klebsiella pneumoniae ATCC-2146 (1 μM), and a 3 log unit reduction for Mycobacterium smegmatis mc2155 (ATCC-700084). A 5 log unit reduction in CFU was observed for Candida albicans ATCC-90028 (1 μM) and Cryptococcus neoformans ATCC-64538 (0.5 μM), and a 3 log unit reduction was noted for Candida glabrata ATCC-15545 (1 μM). Infectivity was reduced by 6 log units in dengue 1 (0.1 μM), by 5 log units (0.5 μM) in vesicular stomatitis virus, and by 2 log units (5 μM) in human adenovirus-5. Overall, the results demonstrate that DIMPy-BODIPY exhibits antiviral, antibacterial and antifungal photodynamic inactivation at nanomolar concentrations and short illumination times. Full article
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Open AccessArticle Integrated LC-MS/MS Analytical Systems and Physical Inspection for the Analysis of a Botanical Herbal Preparation
Molecules 2015, 20(6), 10641-10656; doi:10.3390/molecules200610641
Received: 1 May 2015 / Revised: 1 June 2015 / Accepted: 2 June 2015 / Published: 9 June 2015
Cited by 2 | PDF Full-text (2676 KB) | HTML Full-text | XML Full-text
Abstract
The herbal decoction process is generally inconvenient and unpleasant. To avoid using herbal medicine decoctions, various high-quality industrial and pharmaceutical herbal decoction products have been used in clinical applications for more than ten years in Taiwan. However, the consistency and standardization of the
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The herbal decoction process is generally inconvenient and unpleasant. To avoid using herbal medicine decoctions, various high-quality industrial and pharmaceutical herbal decoction products have been used in clinical applications for more than ten years in Taiwan. However, the consistency and standardization of the quality of these herbal medicines are goals that remain to be achieved. The aim of study was to develop a validated liquid chromatography-tandem electrospray ionization mass spectrometry (LC-MS/MS) method to determine the biomarkers astragaloside I, astragaloside IV, formononetin, cinnamic acid, paeoniflorin and gingerol in the herbal preparation known as Huangqi-Guizhi-Wuwu (HGW). To investigate the physical quality of HGW, methods such as scanning electron microscopy, light microscopy with Congo red and potassium iodine staining, solubility measurements, swelling power tests, and crude fiber analysis were used to identify additives in commercial pharmaceutical products. The optimal LC-MS/MS multiple reaction-monitoring system included a gradient program using 5 mM ammonium acetate buffer with 0.05% formic acid/methanol. The results demonstrate deviations in biomarker content across different brands. In addition to the herbal extract, starch and excipients in the pharmaceutical granule, and crushed crude herb powder was added to the pharmaceutical products to increase their herbal ingredient content. In conclusion, a rigorous examination should be performed to certify the quality of the herbal products. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Computational Studies of Benzoxazinone Derivatives as Antiviral Agents against Herpes Virus Type 1 Protease
Molecules 2015, 20(6), 10689-10704; doi:10.3390/molecules200610689
Received: 28 February 2015 / Revised: 27 May 2015 / Accepted: 1 June 2015 / Published: 10 June 2015
PDF Full-text (2684 KB) | HTML Full-text | XML Full-text
Abstract
Herpes simplex virus infections have been described in the medical literature for centuries, yet the the drugs available nowadays for therapy are largely ineffective and low oral bioavailability plays an important role on the inefficacy of the treatments. Additionally, the details of the
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Herpes simplex virus infections have been described in the medical literature for centuries, yet the the drugs available nowadays for therapy are largely ineffective and low oral bioavailability plays an important role on the inefficacy of the treatments. Additionally, the details of the inhibition of Herpes Virus type 1 are still not fully understood. Studies have shown that several viruses encode one or more proteases required for the production new infectious virions. This study presents an analysis of the interactions between HSV-1 protease and benzoxazinone derivatives through a combination of structure-activity relationships, comparative modeling and molecular docking studies. The structure activity relationship results showed an important contribution of hydrophobic and polarizable groups and limitations for bulky groups in specific positions. Two Herpes Virus type 1 protease models were constructed and compared to achieve the best model which was obtained by MODELLER. Molecular docking results pointed to an important interaction between the most potent benzoxazinone derivative and Ser129, consistent with previous mechanistic data. Moreover, we also observed hydrophobic interactions that may play an important role in the stabilization of inhibitors in the active site. Finally, we performed druglikeness and drugscore studies of the most potent derivatives and the drugs currently used against Herpes virus. Full article
(This article belongs to the Special Issue Molecular Docking in Drug Design)
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Open AccessArticle Preparation, Characterization and Pharmacokinetic Study of Xiangfu Siwu Decoction Essential Oil/β-Cyclodextrin Inclusion Complex
Molecules 2015, 20(6), 10705-10720; doi:10.3390/molecules200610705
Received: 12 May 2015 / Revised: 5 June 2015 / Accepted: 5 June 2015 / Published: 10 June 2015
Cited by 5 | PDF Full-text (1752 KB) | HTML Full-text | XML Full-text
Abstract
Xiang-Fu-Si-Wu Decoction (XFSWD), a famous Chinese herbal formula, is considered an effective prescription for treating primary dysmenorrhea. The essential oil is a significant effective ingredient of XFSWD. However, its volatility, instability and poor water-solubility influence its pharmacodynamic effects. β-Cyclodextrin (β-CD) has the intrinsic
[...] Read more.
Xiang-Fu-Si-Wu Decoction (XFSWD), a famous Chinese herbal formula, is considered an effective prescription for treating primary dysmenorrhea. The essential oil is a significant effective ingredient of XFSWD. However, its volatility, instability and poor water-solubility influence its pharmacodynamic effects. β-Cyclodextrin (β-CD) has the intrinsic ability to form specific inclusion complexes with such drugs to enhance their stability, solubility and bioavailability. The aim of this study was thus to compare the pharmacokinetic characteristics and the oral bioavailability of XFSWD essential oil (XEO) and its β-CD inclusion complex after oral administration to rats. A simple, rapid, and sensitive ultra-high performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was developed for the simultaneous quantification of five active components of XEO in rat plasma. The in vivo data showed that XEO/β-CD inclusion complex displayed higher maximum plasma concentration (Cmax), longer half-time (T1/2) and bigger area under the concentration-time curve (AUC0–24 h). These results demonstrated that the formation of β-CD inclusion complex has significantly increased the oral bioavailability of the drugs in rats than free oil. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Endothelium-Independent Vasorelaxant Effect of Ligusticum jeholense Root and Rhizoma on Rat Thoracic Aorta
Molecules 2015, 20(6), 10721-10733; doi:10.3390/molecules200610721
Received: 23 April 2015 / Revised: 6 June 2015 / Accepted: 8 June 2015 / Published: 10 June 2015
Cited by 2 | PDF Full-text (926 KB) | HTML Full-text | XML Full-text
Abstract
Ligusticum jeholense has been used as the traditional medicine ‘Go-Bon’ (Chinese name, Gao-ben) in China and Korea. Considering the increased use of medicinal herbs to treat hypertension, in this study, we aimed to investigate the mechanisms of the vasorelaxation effect caused by L.
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Ligusticum jeholense has been used as the traditional medicine ‘Go-Bon’ (Chinese name, Gao-ben) in China and Korea. Considering the increased use of medicinal herbs to treat hypertension, in this study, we aimed to investigate the mechanisms of the vasorelaxation effect caused by L. jeholense. We tested the methanol (MeOH) extract of L. jeholense root and rhizoma for vasorelaxant effects; while using an isolated organ-chamber technique, L. jeholense extract (LJE) induced relaxation in the rat aortic rings by stimulating vascular endothelial and smooth muscle cells. LJE showed concentration-dependent relaxant effects on endothelium-intact and endothelium-denuded aortic rings pre-contracted with both phenylephrine (PE) and potassium chloride (KCl) in Krebs-Henseleit (KH) buffer. The vasorelaxant effect of LJE was partly attenuated by pre-treatment with glibenclamide or 4-aminopyridine (4-AP) as K+ channel blockers. Moreover, LJE showed concentration-dependent inhibition of vasoconstriction by Ca2+ supplementation in the aortic rings that were pre-contracted with PE or KCl in Ca2+-free KH buffer. In addition, a combination of LJE and nifedipine, pre-incubated further, decreased PE-induced contractions. The results suggested that LJE-induced vasorelaxation were related to blocking K+ channels and inhibiting entry of extracellular Ca2+ via receptor-operative Ca2+ channels (ROCCs) or voltage-dependent Ca2+ channels (VDCCs). Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Transcriptomic Analysis of Flower Blooming in Jasminum sambac through De Novo RNA Sequencing
Molecules 2015, 20(6), 10734-10747; doi:10.3390/molecules200610734
Received: 7 May 2015 / Revised: 1 June 2015 / Accepted: 8 June 2015 / Published: 10 June 2015
Cited by 3 | PDF Full-text (9167 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Flower blooming is a critical and complicated plant developmental process in flowering plants. However, insufficient information is available about the complex network that regulates flower blooming in Jasminum sambac. In this study, we used the RNA-Seq platform to analyze the molecular regulation
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Flower blooming is a critical and complicated plant developmental process in flowering plants. However, insufficient information is available about the complex network that regulates flower blooming in Jasminum sambac. In this study, we used the RNA-Seq platform to analyze the molecular regulation of flower blooming in J. sambac by comparing the transcript profiles at two flower developmental stages: budding and blooming. A total of 4577 differentially-expressed genes (DEGs) were identified between the two floral stages. The Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses revealed that the DEGs in the “oxidation-reduction process”, “extracellular region”, “steroid biosynthesis”, “glycosphingolipid biosynthesis”, “plant hormone signal transduction” and “pentose and glucuronate interconversions” might be associated with flower development. A total of 103 and 92 unigenes exhibited sequence similarities to the known flower development and floral scent genes from other plants. Among these unigenes, five flower development and 19 floral scent unigenes exhibited at least four-fold differences in expression between the two stages. Our results provide abundant genetic resources for studying the flower blooming mechanisms and molecular breeding of J. sambac. Full article
(This article belongs to the Section Molecular Diversity)
Open AccessArticle Oxidation of Disulfides to Thiolsulfinates with Hydrogen Peroxide and a Cyclic Seleninate Ester Catalyst
Molecules 2015, 20(6), 10748-10762; doi:10.3390/molecules200610748
Received: 24 May 2015 / Revised: 3 June 2015 / Accepted: 4 June 2015 / Published: 11 June 2015
Cited by 5 | PDF Full-text (810 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Cyclic seleninate esters function as mimetics of the antioxidant selenoenzyme glutathione peroxidase. They catalyze the reduction of harmful peroxides with thiols, which are converted to disulfides in the process. The possibility that the seleninate esters could also catalyze the further oxidation of disulfides
[...] Read more.
Cyclic seleninate esters function as mimetics of the antioxidant selenoenzyme glutathione peroxidase. They catalyze the reduction of harmful peroxides with thiols, which are converted to disulfides in the process. The possibility that the seleninate esters could also catalyze the further oxidation of disulfides to thiolsulfinates and other overoxidation products under these conditions was investigated. This has ramifications in potential medicinal applications of seleninate esters because of the possibility of catalyzing the unwanted oxidation of disulfide-containing spectator peptides and proteins. A variety of aryl and alkyl disulfides underwent facile oxidation with hydrogen peroxide in the presence of catalytic benzo-1,2-oxaselenolane Se-oxide affording the corresponding thiolsulfinates as the principal products. Unsymmetrical disulfides typically afforded mixtures of regioisomers. Lipoic acid and N,N-dibenzoylcystine dimethyl ester were oxidized readily under similar conditions. Although isolated yields of the product thiolsulfinates were generally modest, these experiments demonstrate that the method nevertheless has preparative value because of its mild conditions. The results also confirm the possibility that cyclic seleninate esters could catalyze the further undesired oxidation of disulfides in vivo. Full article
(This article belongs to the Special Issue Selenium Catalysts and Antioxidants)
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Open AccessArticle Coarse-Grained Modeling of Peptide Docking Associated with Large Conformation Transitions of the Binding Protein: Troponin I Fragment–Troponin C System
Molecules 2015, 20(6), 10763-10780; doi:10.3390/molecules200610763
Received: 31 March 2015 / Revised: 14 May 2015 / Accepted: 21 May 2015 / Published: 11 June 2015
Cited by 5 | PDF Full-text (6164 KB) | HTML Full-text | XML Full-text
Abstract
Most of the current docking procedures are focused on fine conformational adjustments of assembled complexes and fail to reproduce large-scale protein motion. In this paper, we test a new modeling approach developed to address this problem. CABS-dock is a versatile and efficient tool
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Most of the current docking procedures are focused on fine conformational adjustments of assembled complexes and fail to reproduce large-scale protein motion. In this paper, we test a new modeling approach developed to address this problem. CABS-dock is a versatile and efficient tool for modeling the structure, dynamics and interactions of protein complexes. The docking protocol employs a coarse-grained representation of proteins, a simplified model of interactions and advanced protocols for conformational sampling. CABS-dock is one of the very few tools that allow unrestrained docking with large conformational freedom of the receptor. In an example application we modeled the process of complex assembly between two proteins: Troponin C (TnC) and the N-terminal helix of Troponin I (TnI N-helix), which occurs in vivo during muscle contraction. Docking simulations illustrated how the TnC molecule undergoes significant conformational transition on complex formation, a phenomenon that can be modeled only when protein flexibility is properly accounted for. This way our procedure opens up a new possibility for studying mechanisms of protein complex assembly, which may be a supporting tool for rational drug design. Full article
(This article belongs to the Special Issue Molecular Docking in Drug Design)
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Open AccessArticle Metabolites Produced by the Endophytic Fungus Aspergillus fumigatus from the Stem of Erythrophloeum fordii Oliv.
Molecules 2015, 20(6), 10793-10799; doi:10.3390/molecules200610793
Received: 9 May 2015 / Revised: 26 May 2015 / Accepted: 26 May 2015 / Published: 11 June 2015
Cited by 3 | PDF Full-text (873 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A new diketopiperazine alkaloid named spirotryprostatin K (1), and five known alkaloids, spiro[5H,10H-dipyrrolo[1,2-a:1′,2′-d]pyrazine-2(3H),2′-[2H]-indole]-3′,5,10(1′H) trione (2), 6-methoxyspirotryprostatin B (3), pseurotin A (4), N-β-acetyltryptamine
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A new diketopiperazine alkaloid named spirotryprostatin K (1), and five known alkaloids, spiro[5H,10H-dipyrrolo[1,2-a:1′,2′-d]pyrazine-2(3H),2′-[2H]-indole]-3′,5,10(1′H) trione (2), 6-methoxyspirotryprostatin B (3), pseurotin A (4), N-β-acetyltryptamine (5), and lumichrome (6) were isolated from the endophytic fungus Aspergillus fumigatus. The structure and the absolute configuration of spirotryprostatin K were established by extensive spectroscopic analyses, acid hydrolysis and ECD calculations. Pseurotin A exhibited indirect anti-inflammatory activity by suppressing the lipopolysaccharide-induced proinflammatory factors in BV2 microglial cells, with an IC50 of 5.20 µM. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Comparative Evaluation of Different Extraction Techniques and Solvents for the Assay of Phytochemicals and Antioxidant Activity of Hashemi Rice Bran
Molecules 2015, 20(6), 10822-10838; doi:10.3390/molecules200610822
Received: 14 April 2015 / Revised: 2 June 2015 / Accepted: 4 June 2015 / Published: 11 June 2015
Cited by 6 | PDF Full-text (801 KB) | HTML Full-text | XML Full-text
Abstract
Secondary metabolite contents (total phenolic, flavonoid, tocopherol, and tocotrienol) and antioxidant activities of Hashemi rice bran extracts obtained by ultrasound-assisted and traditional solvent (ethanol and 50:50 (v/v) ethanol-water) extraction techniques were compared. Phenolic and, flavonoid compounds were identified using
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Secondary metabolite contents (total phenolic, flavonoid, tocopherol, and tocotrienol) and antioxidant activities of Hashemi rice bran extracts obtained by ultrasound-assisted and traditional solvent (ethanol and 50:50 (v/v) ethanol-water) extraction techniques were compared. Phenolic and, flavonoid compounds were identified using ultra-high performance liquid chromatography and method validation was performed. Significant differences (p < 0.05) were observed among the different extraction techniques upon comparison of phytochemical contents and antioxidant activities. The extracts obtained using the ethanol-water (50:50 v/v) ultrasonic technique showed the highest amounts of total phenolics (288.40 mg/100 g dry material (DM)), total flavonoids (156.20 mg/100 g DM), and total tocotrienols (56.23 mg/100 g DM), and the highest antioxidant activity (84.21% 1,1-diphenyl-2-picrylhydrazyl (DPPH), 65.27% β-carotene-linoleic bleaching and 82.20% nitric oxide scavenging activity). Secondary metabolite contents and antioxidant activities of the rice bran extracts varied depending of the extraction method used, and according to their effectiveness, these were organized in a decreasing order as follows: ethanol-water (50:50 v/v) ultrasonic, ethanol-water (50:50 v/v) maceration, ethanol ultrasonic and ethanol maceration methods. Ferulic, gallic and chlorogenic acids were the most abundant phenolic compounds in rice bran extracts. The phytochemical constituents of Hashemi rice bran and its antioxidant properties provides insights into its potential application to promote health. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle A Halogen-Containing Stilbene Derivative from the Leaves of Cajanus cajan that Induces Osteogenic Differentiation of Human Mesenchymal Stem Cells
Molecules 2015, 20(6), 10839-10847; doi:10.3390/molecules200610839
Received: 25 April 2015 / Revised: 5 June 2015 / Accepted: 9 June 2015 / Published: 11 June 2015
Cited by 3 | PDF Full-text (1226 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A new natural halogen-containing stilbene derivative was isolated from the leaves of Cajanus cajan (L.) Millsp. and identified as 3-O-(3-chloro-2-hydroxyl-propanyl)-longistylin A by comprehensive spectroscopic and chemical analysis, and named cajanstilbene H (1). It is the first halogen-containing stilbene derivative
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A new natural halogen-containing stilbene derivative was isolated from the leaves of Cajanus cajan (L.) Millsp. and identified as 3-O-(3-chloro-2-hydroxyl-propanyl)-longistylin A by comprehensive spectroscopic and chemical analysis, and named cajanstilbene H (1). It is the first halogen-containing stilbene derivative found from plants. In human mesenchymal stem cells (hMSC) from bone marrow, 1 did not promote cell proliferation, but distinctly enhanced osteogenic differentiation of hMSC in time- and dose-dependent manners. In six human cancer cell lines, 1 showed a moderate inhibitory effect on cell proliferation, with IC50 values of 21.42–25.85 μmol·L−1. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Molecular Cloning, Carbohydrate Specificity and the Crystal Structure of Two Sclerotium rolfsii Lectin Variants
Molecules 2015, 20(6), 10848-10865; doi:10.3390/molecules200610848
Received: 31 March 2015 / Revised: 3 June 2015 / Accepted: 5 June 2015 / Published: 12 June 2015
Cited by 3 | PDF Full-text (2259 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
SRL is a cell wall associated developmental-stage specific lectin secreted by Sclerotium rolfsii, a soil-born pathogenic fungus. SRL displays specificity for TF antigen (Galβ1→3GalNAc-α-Ser//Thr) expressed in all cancer types and has tumour suppressing effects in vivo. Considering the immense potential of
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SRL is a cell wall associated developmental-stage specific lectin secreted by Sclerotium rolfsii, a soil-born pathogenic fungus. SRL displays specificity for TF antigen (Galβ1→3GalNAc-α-Ser//Thr) expressed in all cancer types and has tumour suppressing effects in vivo. Considering the immense potential of SRL in cancer research, we have generated two variant gene constructs of SRL and expressed in E. coli to refine the sugar specificity and solubility by altering the surface charge. SSR1 and SSR2 are two different recombinant variants of SRL, both of which recognize TF antigen but only SSR1 binds to Tn antigen (GalNAcα-Ser/Thr). The glycan array analysis of the variants demonstrated that SSR1 recognizes TF antigen and their derivative with high affinity similar to SRL but showed highest affinity towards the sialylated Tn antigen, unlike SRL. The carbohydrate binding property of SSR2 remains unaltered compared to SRL. The crystal structures of the two variants were determined in free form and in complex with N-acetylglucosamine at 1.7 Å and 1.6 Å resolution, respectively. Structural analysis highlighted the structural basis of the fine carbohydrate specificity of the two SRL variants and results are in agreement with glycan array analysis. Full article
(This article belongs to the Special Issue Protein-Carbohydrate Interactions, and Beyond)
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Open AccessCommunication Selenium-Mediated Synthesis of Tetrasubstituted Naphthalenes through Rearrangement
Molecules 2015, 20(6), 10866-10872; doi:10.3390/molecules200610866
Received: 11 May 2015 / Revised: 8 June 2015 / Accepted: 11 June 2015 / Published: 12 June 2015
PDF Full-text (750 KB) | HTML Full-text | XML Full-text
Abstract
New β-keto ester substituted stilbene derivatives have been synthesized and cyclized with selenium electrophiles in the presence of Lewis acids. This now allows access to 1,2,3,4-tetrasubstituted naphthalene derivatives as cyclization and rearrangement products. Full article
(This article belongs to the Special Issue Selenium Catalysts and Antioxidants)
Open AccessArticle Anti-Schistosomal Activity of Cinnamic Acid Esters: Eugenyl and Thymyl Cinnamate Induce Cytoplasmic Vacuoles and Death in Schistosomula of Schistosoma mansoni
Molecules 2015, 20(6), 10873-10883; doi:10.3390/molecules200610873
Received: 5 May 2015 / Revised: 3 June 2015 / Accepted: 8 June 2015 / Published: 12 June 2015
Cited by 3 | PDF Full-text (2784 KB) | HTML Full-text | XML Full-text
Abstract
Bornyl caffeate (1) was previously isolated by us from Valeriana (V.) wallichii rhizomes and identified as an anti-leishmanial substance. Here, we screened a small compound library of synthesized derivatives 130 for activity against schistosomula of Schistosoma (S.) mansoni.
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Bornyl caffeate (1) was previously isolated by us from Valeriana (V.) wallichii rhizomes and identified as an anti-leishmanial substance. Here, we screened a small compound library of synthesized derivatives 130 for activity against schistosomula of Schistosoma (S.) mansoni. Compound 1 did not show any anti-schistosomal activity. However, strong phenotypic changes, including the formation of vacuoles, degeneration and death were observed after in vitro treatment with compounds 23 (thymyl cinnamate) and 27 (eugenyl cinnamate). Electron microscopy analysis of the induced vacuoles in the dying parasites suggests that 23 and 27 interfere with autophagy. Full article
Open AccessArticle Synthesis of Bicyclic Isoxazoles and Isoxazolines via Intramolecular Nitrile Oxide Cycloaddition
Molecules 2015, 20(6), 10910-10927; doi:10.3390/molecules200610910
Received: 30 April 2015 / Revised: 1 June 2015 / Accepted: 4 June 2015 / Published: 12 June 2015
Cited by 3 | PDF Full-text (908 KB) | HTML Full-text | XML Full-text
Abstract
An efficient and straight forward procedure for the syntheses of bicyclic isoxazole/isoxazoline derivatives from the corresponding dimethyl-2-(2-nitro-1-aryl/alkyl)-2-(prop-2-yn-1yl)malonates or dimethyl 2-allyl-2-(2-nitro-1-aryl/alkyl ethyl)malonate is described. High yields and simple operations are important features of this methodology. Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessArticle Low-Quality Structural and Interaction Data Improves Binding Affinity Prediction via Random Forest
Molecules 2015, 20(6), 10947-10962; doi:10.3390/molecules200610947
Received: 13 March 2015 / Revised: 4 June 2015 / Accepted: 9 June 2015 / Published: 12 June 2015
Cited by 9 | PDF Full-text (962 KB) | HTML Full-text | XML Full-text
Abstract
Docking scoring functions can be used to predict the strength of protein-ligand binding. It is widely believed that training a scoring function with low-quality data is detrimental for its predictive performance. Nevertheless, there is a surprising lack of systematic validation experiments in support
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Docking scoring functions can be used to predict the strength of protein-ligand binding. It is widely believed that training a scoring function with low-quality data is detrimental for its predictive performance. Nevertheless, there is a surprising lack of systematic validation experiments in support of this hypothesis. In this study, we investigated to which extent training a scoring function with data containing low-quality structural and binding data is detrimental for predictive performance. We actually found that low-quality data is not only non-detrimental, but beneficial for the predictive performance of machine-learning scoring functions, though the improvement is less important than that coming from high-quality data. Furthermore, we observed that classical scoring functions are not able to effectively exploit data beyond an early threshold, regardless of its quality. This demonstrates that exploiting a larger data volume is more important for the performance of machine-learning scoring functions than restricting to a smaller set of higher data quality. Full article
(This article belongs to the Special Issue Chemoinformatics)
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Open AccessArticle A Selective G-Quadruplex DNA-Stabilizing Ligand Based on a Cyclic Naphthalene Diimide Derivative
Molecules 2015, 20(6), 10963-10979; doi:10.3390/molecules200610963
Received: 8 May 2015 / Revised: 28 May 2015 / Accepted: 8 June 2015 / Published: 12 June 2015
Cited by 9 | PDF Full-text (2743 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A cyclic naphthalene diimide (cyclic NDI, 1), carrying a benzene moiety as linker chain, was synthesized and its interaction with G-quadruplex DNAs of a-core and a-coreTT as a human telomeric DNA, c-kit and c-myc as DNA sequence at promoter region, or thrombin-binding
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A cyclic naphthalene diimide (cyclic NDI, 1), carrying a benzene moiety as linker chain, was synthesized and its interaction with G-quadruplex DNAs of a-core and a-coreTT as a human telomeric DNA, c-kit and c-myc as DNA sequence at promoter region, or thrombin-binding aptamer (TBA) studied based on UV-VIS and circular dichroism (CD) spectroscopic techniques, thermal melting temperature measurement, and FRET-melting assay. The circular dichroism spectra showed that 1 induced the formation of different types of G-quadruplex DNA structure. Compound 1 bound to these G-quadruplexes with affinities in the range of 106–107 M−1 order and a 2:1 stoichiometry. Compound 1 showed 270-fold higher selectivity for a-core than dsDNA with a preferable a-core binding than a-coreTT, c-kit, c-myc and TBA in the presence of K+, which is supported by thermal melting studies. The FRET-melting assay also showed that 1 bound preferentially to human telomeric DNA. Compound 1 showed potent inhibition against telomerase activity with an IC50 value of 0.9 μM and preferable binding to G-quadruplexes DNA than our previously published cyclic NDI derivative 3 carrying a benzene moiety as longer linker chain. Full article
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Open AccessArticle Volatile Compounds from Grape Skin, Juice and Wine from Five Interspecific Hybrid Grape Cultivars Grown in Québec (Canada) for Wine Production
Molecules 2015, 20(6), 10980-11016; doi:10.3390/molecules200610980
Received: 25 March 2015 / Accepted: 3 June 2015 / Published: 15 June 2015
Cited by 14 | PDF Full-text (1380 KB) | HTML Full-text | XML Full-text
Abstract
Developed from crosses between Vitis vinifera and North American Vitis species, interspecific hybrid grape varieties are becoming economically significant in northern areas, where they are now extensively grown for wine production. However, the varietal differences between interspecific hybrids are not well defined, nor
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Developed from crosses between Vitis vinifera and North American Vitis species, interspecific hybrid grape varieties are becoming economically significant in northern areas, where they are now extensively grown for wine production. However, the varietal differences between interspecific hybrids are not well defined, nor are the relationships between hybrid grape and wine composition, which causes significant drawbacks in the development of viticulture and winemaking of northern wines. In an effort to increase our understanding of interspecific hybrids, we have characterized the free volatile compounds profiles of berries (juice and skin) and wines of five red hybrid varieties (Frontenac, Marquette, Maréchal Foch, Sabrevois and St. Croix) grown in Québec (Canada), using GC-MS(TOF)-SPME. In grapes and wines, significantly higher levels of C6 and other fatty acid degradation products (FADP) were found in Frontenac, Maréchal Foch and Marquette. Terpenes were primarily located in the skin, with Marquette showing the highest level for these compounds. Both the level of terpenes and the level of FADP in grape were strongly correlated with their respective levels in wine, as demonstrated by the redundancy analyses. Nonanal, (E,Z)-2,6-nonadienal, β-damascenone, ethyl octanoate and isoamyl acetate showed the highest OAVs in the wines of the studied varieties. Full article
(This article belongs to the collection Wine Chemistry)
Open AccessArticle In Vivo Nanodetoxication for Acute Uranium Exposure
Molecules 2015, 20(6), 11017-11033; doi:10.3390/molecules200611017
Received: 24 March 2015 / Revised: 28 May 2015 / Accepted: 1 June 2015 / Published: 15 June 2015
Cited by 1 | PDF Full-text (1678 KB) | HTML Full-text | XML Full-text
Abstract
Accidental exposure to uranium is a matter of concern, as U(VI) is nephrotoxic in both human and animal models, and its toxicity is associated to chemical toxicity instead of radioactivity. We synthesized different PAMAM G4 and G5 derivatives in order to prove their
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Accidental exposure to uranium is a matter of concern, as U(VI) is nephrotoxic in both human and animal models, and its toxicity is associated to chemical toxicity instead of radioactivity. We synthesized different PAMAM G4 and G5 derivatives in order to prove their interaction with uranium and their effect on the viability of red blood cells in vitro. Furthermore, we prove the effectiveness of the selected dendrimers in an animal model of acute uranium intoxication. The dendrimer PAMAM G4-Lys-Fmoc-Cbz demonstrated the ability to chelate the uranyl ion in vivo, improving the biochemical and histopathologic features caused by acute intoxication with uranium. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Physical Properties, Antioxidant and Antimicrobial Activity of Chitosan Films Containing Carvacrol and Pomegranate Peel Extract
Molecules 2015, 20(6), 11034-11045; doi:10.3390/molecules200611034
Received: 4 May 2015 / Revised: 8 June 2015 / Accepted: 9 June 2015 / Published: 15 June 2015
Cited by 15 | PDF Full-text (1573 KB) | HTML Full-text | XML Full-text
Abstract
Chitosan-based active films were developed by incorporation of carvacrol (10 g/L), pomegranate peel extract (PPE, 10 g/L) and carvacrol + PPE (10 g/L of each) and their physical, antioxidant and antimicrobial properties were investigated. Incorporation of carvacrol and carvacrol + PPE into the
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Chitosan-based active films were developed by incorporation of carvacrol (10 g/L), pomegranate peel extract (PPE, 10 g/L) and carvacrol + PPE (10 g/L of each) and their physical, antioxidant and antimicrobial properties were investigated. Incorporation of carvacrol and carvacrol + PPE into the films significantly decreased the water vapor permeability, tensile strength and percentage of elongation at break. Incorporation of carvacrol, PPE and carvacrol + PPE into the films decreased the transparency, but significantly increased the total phenol content and antioxidant activity. All the films, with the exception of PPE-incorporated film, exhibited antibacterial activity against Escherichia coli and Staphylococcus aureus. In addition, the antibacterial activity against Staphylococcus aureus of the film incorporated with carvacrol + PPE was moderately higher than that incorporated with carvacrol or PPE alone, suggesting a synergistic action between carvacrol and PPE. Full article
Open AccessArticle New Polyphenols Identified in Artemisiae abrotani herba Extract
Molecules 2015, 20(6), 11063-11075; doi:10.3390/molecules200611063
Received: 2 May 2015 / Revised: 27 May 2015 / Accepted: 8 June 2015 / Published: 15 June 2015
Cited by 3 | PDF Full-text (785 KB) | HTML Full-text | XML Full-text
Abstract
Artemisia abrotanum L. (“southernwood”) belongs to the Artemisia genus and it is used in traditional medicine for the treatment of a variety of illnesses. Scarce data is available on the chemical composition of this medicinal plant, most research being focused on the quantitative
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Artemisia abrotanum L. (“southernwood”) belongs to the Artemisia genus and it is used in traditional medicine for the treatment of a variety of illnesses. Scarce data is available on the chemical composition of this medicinal plant, most research being focused on the quantitative and qualitative analyses of its essential oil. Our aim was to investigate the content and profile of polyphenols, flavonoids and hydroxycinnamic derivatives present in the Artemisiae abrotani herba extract. We conducted LC/MS analysis and we screened for 19 polyphenols, flavonoids and hydroxycinnamic derivatives. We determined the total content of these compounds and we screened for antioxidant activity. Most polyphenol acids, hydroxycinnamic derivatives and flavonoids were identified and quantified for the first time in this study. We found an original polyphenol distribution profile with high concentration of sinapic acid, rutin, quercetol, ferulic acid and patuletin. We measured the antioxidant activity, the ethanolic extract presenting a modest radical scavenging activity. The value of this study consists in its novelty as it adds new data on the chemical composition of A. abrotanum L. and it opens novel perspectives for medical and nutritional applications of this plant. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Negative-Pressure Cavitation Extraction of Secoisolariciresinol Diglycoside from Flaxseed Cakes
Molecules 2015, 20(6), 11076-11089; doi:10.3390/molecules200611076
Received: 18 May 2015 / Accepted: 10 June 2015 / Published: 15 June 2015
Cited by 1 | PDF Full-text (2743 KB) | HTML Full-text | XML Full-text
Abstract
The negative-pressure cavitation extraction (NPCE) technique was applied firstly to extract secoisolariciresinol diglucoside (SDG) from flaxseed cakes. The significant extraction parameters were screened by fractional factorial design (FFD). The optimal parameters were determined using the central composite design (CCD) with the two variables,
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The negative-pressure cavitation extraction (NPCE) technique was applied firstly to extract secoisolariciresinol diglucoside (SDG) from flaxseed cakes. The significant extraction parameters were screened by fractional factorial design (FFD). The optimal parameters were determined using the central composite design (CCD) with the two variables, NaOH amount and the liquid/solid ratio. The conditions of the extraction were optimized by using response surface methodology (RSM). Under the optimal conditions, the extraction yield and the extraction purity of SDG was 16.25 mg/g and 3.86%, respectively. The efficiency of NPCE was compared with that of conventional extraction methods. Our results demonstrated that NPCE was comparable to the well-known ultrasound-assisted extraction in term of extraction yield and purity. This extraction technique has advantages of less time-consuming, low solvent usage and high throughput capability. Full article
(This article belongs to the Special Issue New Technologies for the Recovery of Natural Products)
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Open AccessArticle Anthocyanin and Carotenoid Contents in Different Cultivars of Chrysanthemum (Dendranthema grandiflorum Ramat.) Flower
Molecules 2015, 20(6), 11090-11102; doi:10.3390/molecules200611090
Received: 17 April 2015 / Revised: 3 June 2015 / Accepted: 4 June 2015 / Published: 15 June 2015
Cited by 4 | PDF Full-text (1878 KB) | HTML Full-text | XML Full-text
Abstract
The flowers of twenty-three cultivars of Dendranthema grandiflorum Ramat. were investigated to determine anthocyanin and carotenoid levels and to confirm the effects of the pigments on the flower colors using high-performance liquid chromatography (HPLC) and electrospray ionization-mass spectrometry (ESI-MS). The cultivars contained the
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The flowers of twenty-three cultivars of Dendranthema grandiflorum Ramat. were investigated to determine anthocyanin and carotenoid levels and to confirm the effects of the pigments on the flower colors using high-performance liquid chromatography (HPLC) and electrospray ionization-mass spectrometry (ESI-MS). The cultivars contained the anthocyanins cyanidin 3-glucoside (C3g) and cyanidin 3-(3ʺ-malonoyl) glucoside (C3mg) and the following carotenoids: lutein, zeaxanthin, β-cryptoxanthin, 13-cis-β-carotene, α-carotene, trans-β-carotene, and 9-cis-β-carotene. The cultivar “Magic” showed the greatest accumulation of total and individual anthocyanins, including C3g and C3gm. On the other hand, the highest level of lutein and zeaxanthin was noted in the cultivar “Il Weol”. The cultivar “Anastasia” contained the highest amount of carotenoids such as trans-β-carotene, 9-cis-β-carotene, and 13-cis-β-carotene. The highest accumulation of β-cryptoxanthin and α-carotene was noted in the cultivar “Anastasia” and “Il Weol”. Our results suggested that ‘Magic”, “Angel” and “Relance’ had high amounts of anthocyanins and showed a wide range of red and purple colors in their petals, whereas “Il Weol’, “Popcorn Ball’ and “Anastasia” produced higher carotenoid contents and displayed yellow or green petal colors. Interestingly, “Green Pang Pang”, which contained a high level of anthocyanins and a medium level of carotenoids, showed the deep green colored petals. “Kastelli”, had high level of carotenoids as well as a medium level of anthocyanins and showed orange and red colored petals. It was concluded that each pigment is responsible for the petal’s colors and the compositions of the pigments affect their flower colors and that the cultivars could be a good source for pharmaceutical, floriculture, and pigment industries. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Solid Lipid Nanoparticles: A Potential Multifunctional Approach towards Rheumatoid Arthritis Theranostics
Molecules 2015, 20(6), 11103-11118; doi:10.3390/molecules200611103
Received: 28 April 2015 / Accepted: 12 June 2015 / Published: 16 June 2015
Cited by 9 | PDF Full-text (2774 KB) | HTML Full-text | XML Full-text
Abstract
Rheumatoid arthritis (RA) is the most common joint-related autoimmune disease and one of the most severe. Despite intensive investigation, the RA inflammatory process remains largely unknown and finding effective and long lasting therapies that specifically target RA is a challenging task. This study
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Rheumatoid arthritis (RA) is the most common joint-related autoimmune disease and one of the most severe. Despite intensive investigation, the RA inflammatory process remains largely unknown and finding effective and long lasting therapies that specifically target RA is a challenging task. This study proposes a different approach for RA therapy, taking advantage of the new emerging field of nanomedicine to develop a targeted theranostic system for intravenous administration, using solid lipid nanoparticles (SLN), a biocompatible and biodegradable colloidal delivery system, surface-functionalized with an anti-CD64 antibody that specifically targets macrophages in RA. Methotrexate (MTX) and superparamagnetic iron oxide nanoparticles (SPIONs) were co-encapsulated inside the SLNs to be used as therapeutic and imaging agents, respectively. All the formulations presented sizes under 250 nm and zeta potential values lower than −16 mV, suitable characteristics for intravenous administration. Transmission electron microscopy (TEM) photographs indicated that the SPIONs were encapsulated inside the SLN matrix and MTX association efficiency values were higher than 98%. In vitro studies, using THP-1 cells, demonstrated that all formulations presented low cytotoxicity at concentrations lower than 500 μg/mL. It was proven that the proposed NPs were not cytotoxic, that both a therapeutic and imaging agent could be co-encapsulated and that the SLN could be functionalized for a potential future application such as anti-body specific targeting. The proposed formulations are, therefore, promising candidates for future theranostic applications. Full article
(This article belongs to the collection Nanomedicine)
Open AccessArticle Antibacterial Activities and Antibacterial Mechanism of Polygonum cuspidatum Extracts against Nosocomial Drug-Resistant Pathogens
Molecules 2015, 20(6), 11119-11130; doi:10.3390/molecules200611119
Received: 3 May 2015 / Accepted: 12 June 2015 / Published: 16 June 2015
Cited by 5 | PDF Full-text (1818 KB) | HTML Full-text | XML Full-text
Abstract
Recently, drug resistance due to the extensive abuse and over-use of antibiotics has become an increasingly serious problem, making the development of alternative antibiotics a very urgent issue. In this study, the Chinese herbal medicine, Polygonum cuspidatum, was extracted with 95% ethanol
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Recently, drug resistance due to the extensive abuse and over-use of antibiotics has become an increasingly serious problem, making the development of alternative antibiotics a very urgent issue. In this study, the Chinese herbal medicine, Polygonum cuspidatum, was extracted with 95% ethanol and the crude extracts were further purified by partition based on solvent polarity. The antimicrobial activities of the extracts and fractions were determined by the disk diffusion and minimum inhibitory concentration (MIC) methods. The results showed that the ethyl ether fraction (EE) of the ethanol extracts possesses a broader antimicrobial spectrum and greater antimicrobial activity against all of the tested clinical drug-resistant isolates, with a range of MIC values between 0.1–3.5 mg/mL. The active extract showed complete inhibition of pathogen growth and did not induce resistance to the active components. In addition, according to scanning electron microscope observations, EE resulted in greater cell morphological changes by degrading and disrupting the cell wall and cytoplasmic membrane, whereby ultimately this cell membrane integrity damage led to cell death. In conclusion, the EE extracts from Polygonum cuspidatum may provide a promising antimicrobial agent for therapeutic applications against nosocomial drug-resistant bacteria. Full article
Open AccessArticle A New Green Ionic Liquid-Based Corrosion Inhibitor for Steel in Acidic Environments
Molecules 2015, 20(6), 11131-11153; doi:10.3390/molecules200611131
Received: 16 April 2015 / Revised: 22 May 2015 / Accepted: 9 June 2015 / Published: 17 June 2015
Cited by 5 | PDF Full-text (1988 KB) | HTML Full-text | XML Full-text
Abstract
This work examines the use of new hydrophobic ionic liquid derivatives, namely octadecylammonium tosylate (ODA-TS) and oleylammonium tosylate (OA-TS) for corrosion protection of steel in 1 M hydrochloric acid solution. Their chemical structures were determined from NMR analyses. The surface activity characteristics of
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This work examines the use of new hydrophobic ionic liquid derivatives, namely octadecylammonium tosylate (ODA-TS) and oleylammonium tosylate (OA-TS) for corrosion protection of steel in 1 M hydrochloric acid solution. Their chemical structures were determined from NMR analyses. The surface activity characteristics of the prepared ODA-TS and OA-TS were evaluated from conductance, surface tension and contact angle measurements. The data indicate the presence of a double bond in the chemical structure of OA-TS modified its surface activity parameters. Potentiodynamic polarization, electrochemical impedance spectroscopy (EIS) measurements, scanning electron microscope (SEM), Energy dispersive X-rays (EDX) analysis and contact angle measurements were utilized to investigate the corrosion protection performance of ODA-TS and OA-TS on steel in acidic solution. The OA-TS and ODA-TS compounds showed good protection performance in acidic chloride solution due to formation of an inhibitive film on the steel surface. Full article
(This article belongs to the Section Molecular Diversity)
Open AccessArticle Non-Invasive Biomarkers for Duchenne Muscular Dystrophy and Carrier Detection
Molecules 2015, 20(6), 11154-11172; doi:10.3390/molecules200611154
Received: 28 February 2015 / Revised: 2 June 2015 / Accepted: 8 June 2015 / Published: 17 June 2015
Cited by 7 | PDF Full-text (1589 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Non-invasive biological indicators of the absence/presence or progress of the disease that could be used to support diagnosis and to evaluate the effectiveness of treatment are of utmost importance in Duchenne Muscular Dystrophy (DMD). This neuromuscular disorder affects male children, causing weakness and
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Non-invasive biological indicators of the absence/presence or progress of the disease that could be used to support diagnosis and to evaluate the effectiveness of treatment are of utmost importance in Duchenne Muscular Dystrophy (DMD). This neuromuscular disorder affects male children, causing weakness and disability, whereas female relatives are at risk of being carriers of the disease. A biomarker with both high sensitivity and specificity for accurate prediction is preferred. Until now creatine kinase (CK) levels have been used for DMD diagnosis but these fail to assess disease progression. Herein we examined the potential applicability of serum levels of matrix metalloproteinase 9 (MMP-9) and matrix metalloproteinase 2 (MMP-2), tissue inhibitor of metalloproteinases 1 (TIMP-1), myostatin (GDF-8) and follistatin (FSTN) as non-invasive biomarkers to distinguish between DMD steroid naïve patients and healthy controls of similar age and also for carrier detection. Our data suggest that serum levels of MMP-9, GDF-8 and FSTN are useful to discriminate DMD from controls (p < 0.05), to correlate with some neuromuscular assessments for DMD, and also to differentiate between Becker muscular dystrophy (BMD) and Limb-girdle muscular dystrophy (LGMD) patients. In DMD individuals under steroid treatment, GDF-8 levels increased as FSTN levels decreased, resembling the proportions of these proteins in healthy controls and also the baseline ratio of patients without steroids. GDF-8 and FSTN serum levels were also useful for carrier detection (p < 0.05). Longitudinal studies with larger cohorts are necessary to confirm that these molecules correlate with disease progression. The biomarkers presented herein could potentially outperform CK levels for carrier detection and also harbor potential for monitoring disease progression. Full article
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Open AccessArticle Protein Tyrosine Phosphatase 1B Inhibitors from the Roots of Cudrania tricuspidata
Molecules 2015, 20(6), 11173-11183; doi:10.3390/molecules200611173
Received: 20 April 2015 / Revised: 11 June 2015 / Accepted: 12 June 2015 / Published: 17 June 2015
Cited by 8 | PDF Full-text (779 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A chemical investigation of the methanol extract from the roots of Cudrania tricuspidata resulted in the isolation of 16 compounds, including prenylated xanthones 19 and flavonoids 1016. Their structures were identified by NMR spectroscopy and mass spectrometry and
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A chemical investigation of the methanol extract from the roots of Cudrania tricuspidata resulted in the isolation of 16 compounds, including prenylated xanthones 19 and flavonoids 1016. Their structures were identified by NMR spectroscopy and mass spectrometry and comparisons with published data. Compounds 19 and 1316 significantly inhibited PTP1B activity in a dose dependent manner, with IC50 values ranging from 1.9–13.6 μM. Prenylated xanthones showed stronger PTP1B inhibitory effects than the flavonoids, suggesting that they may be promising targets for the future discovery of novel PTP1B inhibitors. Furthermore, kinetic analyses indicated that compounds 1 and 13 inhibited PTP1B in a noncompetitive manner; therefore, they may be potential lead compounds in the development of anti-obesity and -diabetic agents. Full article
(This article belongs to the Special Issue Coumarins, Xanthones and Related Compounds)
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Open AccessArticle A Novel Aqueous Two Phase System Composed of Surfactant and Xylitol for the Purification of Lipase from Pumpkin (Cucurbita moschata) Seeds and Recycling of Phase Components
Molecules 2015, 20(6), 11184-11201; doi:10.3390/molecules200611184
Received: 16 April 2015 / Revised: 21 April 2015 / Accepted: 12 June 2015 / Published: 17 June 2015
Cited by 3 | PDF Full-text (1189 KB) | HTML Full-text | XML Full-text
Abstract
Lipase is one of the more important enzymes used in various industries such as the food, detergent, pharmaceutical, textile, and pulp and paper sectors. A novel aqueous two-phase system composed of surfactant and xylitol was employed for the first time to purify lipase
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Lipase is one of the more important enzymes used in various industries such as the food, detergent, pharmaceutical, textile, and pulp and paper sectors. A novel aqueous two-phase system composed of surfactant and xylitol was employed for the first time to purify lipase from Cucurbita moschata. The influence of different parameters such as type and concentration of surfactants, and the composition of the surfactant/xylitol mixtures on the partitioning behavior and recovery of lipase was investigated. Moreover, the effect of system pH and crude load on the degree of purification and yield of the purified lipase were studied. The results indicated that the lipase was partitioned into the top surfactant rich phase while the impurities partitioned into the bottom xylitol-rich phase using an aqueous two phase system composed of 24% (w/w) Triton X-100 and 20% (w/w) xylitol, at 56.2% of tie line length (TLL), (TTL is one of the important parameters in this study and it is determined from a bimodal curve in which the tie-line connects two nodes on the bimodal, that represent concentration of phase components in the top and bottom phases) and a crude load of 25% (w/w) at pH 8.0. Recovery and recycling of components was also measured in each successive step process. The enzyme was successfully recovered by the proposed method with a high purification factor of 16.4 and yield of 97.4% while over 97% of the phase components were also recovered and recycled. This study demonstrated that the proposed novel aqueous two phase system method is more efficient and economical than the traditional aqueous two phase system method for the purification and recovery of the valuable enzyme lipase. Full article
Open AccessArticle Cornus mas (Linnaeus) Novel Devised Medicinal Preparations: Bactericidal Effect against Staphylococcus aureus and Pseudomonas aeruginosa
Molecules 2015, 20(6), 11202-11218; doi:10.3390/molecules200611202
Received: 24 April 2015 / Revised: 8 June 2015 / Accepted: 12 June 2015 / Published: 17 June 2015
Cited by 3 | PDF Full-text (1496 KB) | HTML Full-text | XML Full-text
Abstract
The medicinal properties of Cornus mas L. (=Cornus mascula L.), Cornaceae, are well described in Hippocratian documents, and recent research provides experimental evidence for some of these properties. However, the chemical components of Cornus mas L. that may be of pharmaceutical importance
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The medicinal properties of Cornus mas L. (=Cornus mascula L.), Cornaceae, are well described in Hippocratian documents, and recent research provides experimental evidence for some of these properties. However, the chemical components of Cornus mas L. that may be of pharmaceutical importance are relatively unstable. In this respect a novel methodology for plant nutrient element extraction that provides favorable conditions for simultaneous stabilization of such fragile and unstable structures has been devised. Using this methodology, medicinal preparations derived from Cornus mas L. fresh fruits, proved to possess significant antimicrobial activity selective against S. aureus and P. aeruginosa. This effect became apparent with the addition of sodium bromide in the extraction procedure and varied with the ion availability during extraction. The identification of novel agents with potent antimicrobial activity against these species is of medical importance to overcome the problem of universal antibiotic resistance. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Topical Anti-inflammatory Activity of New Hybrid Molecules of Terpenes and Synthetic Drugs
Molecules 2015, 20(6), 11219-11235; doi:10.3390/molecules200611219
Received: 8 April 2015 / Revised: 28 May 2015 / Accepted: 11 June 2015 / Published: 18 June 2015
Cited by 4 | PDF Full-text (757 KB) | HTML Full-text | XML Full-text
Abstract
The aim of the study was to assess changes in the activity of anti-inflammatory terpenes from Chilean medicinal plants after the formation of derivatives incorporating synthetic anti-inflammatory agents. Ten new hybrid molecules were synthesized combining terpenes (ferruginol (1), imbricatolic acid (
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The aim of the study was to assess changes in the activity of anti-inflammatory terpenes from Chilean medicinal plants after the formation of derivatives incorporating synthetic anti-inflammatory agents. Ten new hybrid molecules were synthesized combining terpenes (ferruginol (1), imbricatolic acid (2) and oleanolic acid (3)) with ibuprofen (4) or naproxen (5). The topical anti-inflammatory activity of the compounds was assessed in mice by the arachidonic acid (AA) and 12-O-tetradecanoyl phorbol 13-acetate (TPA) induced ear edema assays. Basal cytotoxicity was determined towards human lung fibroblasts, gastric epithelial cells and hepatocytes. At 1.4 µmol/mouse, a strong anti-inflammatory effect in the TPA assay was observed for oleanoyl ibuprofenate 12 (79.9%) and oleanoyl ibuprofenate methyl ester 15 (80.0%). In the AA assay, the best activity was observed for 12 at 3.2 µmol/mouse, with 56.8% reduction of inflammation, in the same range as nimesulide (48.9%). All the terpenyl-synthetic anti-inflammatory hybrids showed better effects in the TPA assay, with best activity for 6, 12 and 15. The cytotoxicity of the compounds 8 and 10 with a free COOH, was higher than that of 2. The derivatives from 3 were less toxic than the triterpene. Several of the new compounds presented better anti-inflammatory effect and lower cytotoxicity than the parent terpenes. Full article
(This article belongs to the Section Molecular Diversity)
Open AccessArticle Understanding the Mechanism of Action of Triazine-Phosphonate Derivatives as Flame Retardants for Cotton Fabric
Molecules 2015, 20(6), 11236-11256; doi:10.3390/molecules200611236
Received: 14 February 2015 / Revised: 4 June 2015 / Accepted: 11 June 2015 / Published: 18 June 2015
Cited by 3 | PDF Full-text (1927 KB) | HTML Full-text | XML Full-text
Abstract
Countless hours of research and studies on triazine, phosphonate, and their combination have provided insightful information into their flame retardant properties on polymeric systems. However, a limited number of studies shed light on the mechanism of flame retardancy of their combination on cotton
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Countless hours of research and studies on triazine, phosphonate, and their combination have provided insightful information into their flame retardant properties on polymeric systems. However, a limited number of studies shed light on the mechanism of flame retardancy of their combination on cotton fabrics. The purpose of this research is to gain an understanding of the thermal degradation process of two triazine-phosphonate derivatives on cotton fabric. The investigation included the preparation of diethyl 4,6-dichloro-1,3,5-triazin-2-ylphosphonate (TPN1) and dimethyl (4,6-dichloro-1,3,5-triazin-2-yloxy) methyl phosphonate (TPN3), their application on fabric materials, and the studies of their thermal degradation mechanism. The studies examined chemical components in both solid and gas phases by using attenuated total reflection infrared (ATR-IR) spectroscopy, thermogravimetric analysis coupled with Fourier transform infrared (TGA-FTIR) spectroscopy, and 31P solid state nuclear magnetic resonance (31P solid state NMR), in addition to the computational studies of bond dissociation energy (BDE). Despite a few differences in their decomposition, TPN1 and TPN3 produce one common major product that is believed to help reduce the flammability of the fabric. Full article
(This article belongs to the Special Issue New Trends in Cellulose and Chitin Chemistry)
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Open AccessArticle Phytochemical Profiling and Evaluation of Pharmacological Activities of Hypericum scabrum L.
Molecules 2015, 20(6), 11257-11271; doi:10.3390/molecules200611257
Received: 17 May 2015 / Revised: 12 June 2015 / Accepted: 16 June 2015 / Published: 18 June 2015
Cited by 8 | PDF Full-text (738 KB) | HTML Full-text | XML Full-text
Abstract
Phytochemical investigations of ethyl acetate-soluble part of the aerial part of Hypericum scabrum L. delivered eight pure phenolic compounds 18. The pure compounds were identified through physico-chemical, NMR (1D, 2D) and mass spectrometric studies as: 3-8′′-bisapigenin (1), quercetin
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Phytochemical investigations of ethyl acetate-soluble part of the aerial part of Hypericum scabrum L. delivered eight pure phenolic compounds 18. The pure compounds were identified through physico-chemical, NMR (1D, 2D) and mass spectrometric studies as: 3-8′′-bisapigenin (1), quercetin (2), quercetin-3-O-α-l-arabinofuranoside (3), quercetin-3-O-α-l-rhamnoside (4), quercetin-3-O-β-d-glucopyranoside (5), quercetin-3-O-β-d-galactopyranoside (6), (−)-epicatechin (7), (+)-catechin (8). Total polyphenolic compounds and total flavonoids contents were determined in the extract as 0.107 mg∙mg−1 and 0.023 mg∙mg−1 of the dried extract, respectively. Antioxidant activity using DPPH free radical scavenging assay delivered very strong activity for compounds 2 and 5, 6 and crude extract 10. Protein tyrosine phosphatase 1B (PTP-1B) inhibition experiment of isolated compounds and crude extracts resulted in significant inhibition activity for samples 2, 7a, 8a, 11 and 12 with IC50 values ranging from 1.57 to 2.91 µM. Antimicrobial activity of the pure compounds and extracts produced average results against Staphylococcus aureus, Escherichia coli and Candida albicans strains. From our literature survey, it appears that all pure compounds except 2 were isolated and reported for the first time in H. scabrum. Full article
Open AccessArticle Selected Compounds Structurally Related to Acyclic Sesquiterpenoids and Their Antibacterial and Cytotoxic Activity
Molecules 2015, 20(6), 11272-11296; doi:10.3390/molecules200611272
Received: 30 April 2015 / Revised: 12 June 2015 / Accepted: 15 June 2015 / Published: 18 June 2015
PDF Full-text (2806 KB) | HTML Full-text | XML Full-text
Abstract
By implementing a common and industrially used method, 30 compounds which are structurally related to geranyl acetone, nerolidol, farnesal, farnesol and farnesyl acetate were obtained. Their antimicrobial activity against Staphylococcus aureus, Enterococcus faecalis, Enterococcus faecium, Escherichia coli, Klebsiella pneumoniae
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By implementing a common and industrially used method, 30 compounds which are structurally related to geranyl acetone, nerolidol, farnesal, farnesol and farnesyl acetate were obtained. Their antimicrobial activity against Staphylococcus aureus, Enterococcus faecalis, Enterococcus faecium, Escherichia coli, Klebsiella pneumoniae and Acinetobacter baumannii bacteria was investigated. Pharmacophore models were proposed based on the obtained results and 3D QSAR modelling. Cytotoxic effects against mainly human immortalised and normal cell lines of different origin (malignant melanoma MeWo, colorectal adenocarcinoma HT29, promyelocytic leukemia HL60, gingival fibroblasts HFIG, skin keratinocytes HaCaT and rat small intestine epithelium IEC6) were examined. The odour descriptions of newly synthesised compounds are given. Full article
(This article belongs to the Section Organic Synthesis)
Open AccessArticle Triel Bonds, π-Hole-π-Electrons Interactions in Complexes of Boron and Aluminium Trihalides and Trihydrides with Acetylene and Ethylene
Molecules 2015, 20(6), 11297-11316; doi:10.3390/molecules200611297
Received: 30 April 2015 / Accepted: 15 June 2015 / Published: 19 June 2015
Cited by 19 | PDF Full-text (1224 KB) | HTML Full-text | XML Full-text
Abstract
MP2/aug-cc-pVTZ calculations were performed on complexes of aluminium and boron trihydrides and trihalides with acetylene and ethylene. These complexes are linked through triel bonds where the triel center (B or Al) is characterized by the Lewis acid properties through its π-hole region while
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MP2/aug-cc-pVTZ calculations were performed on complexes of aluminium and boron trihydrides and trihalides with acetylene and ethylene. These complexes are linked through triel bonds where the triel center (B or Al) is characterized by the Lewis acid properties through its π-hole region while π-electrons of C2H2 or C2H4 molecule play the role of the Lewis base. Some of these interactions possess characteristics of covalent bonds, i.e., the Al-π-electrons links as well as the interaction in the BH3-C2H2 complex. The triel-π-electrons interactions are classified sometimes as the 3c-2e bonds. In the case of boron trihydrides, these interactions are often the preliminary stages of the hydroboration reaction. The Quantum Theory of “Atoms in Molecules” as well as the Natural Bond Orbitals approach are applied here to characterize the π-hole-π-electrons interactions. Full article
(This article belongs to the Special Issue Noncovalent pi-Interactions)
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Open AccessArticle Comparative Label-Free Mass Spectrometric Analysis of Mildly versus Severely Affected mdx Mouse Skeletal Muscles Identifies Annexin, Lamin, and Vimentin as Universal Dystrophic Markers
Molecules 2015, 20(6), 11317-11344; doi:10.3390/molecules200611317
Received: 7 May 2015 / Revised: 10 June 2015 / Accepted: 12 June 2015 / Published: 19 June 2015
Cited by 14 | PDF Full-text (3051 KB) | HTML Full-text | XML Full-text
Abstract
The primary deficiency in the membrane cytoskeletal protein dystrophin results in complex changes in dystrophic muscles. In order to compare the degree of secondary alterations in differently affected subtypes of skeletal muscles, we have conducted a global analysis of proteome-wide changes in various
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The primary deficiency in the membrane cytoskeletal protein dystrophin results in complex changes in dystrophic muscles. In order to compare the degree of secondary alterations in differently affected subtypes of skeletal muscles, we have conducted a global analysis of proteome-wide changes in various dystrophin-deficient muscles. In contrast to the highly degenerative mdx diaphragm muscle, which showed considerable alterations in 35 distinct proteins, the spectrum of mildly to moderately dystrophic skeletal muscles, including interosseus, flexor digitorum brevis, soleus, and extensor digitorum longus muscle, exhibited a smaller number of changed proteins. Compensatory mechanisms and/or cellular variances may be responsible for differing secondary changes in individual mdx muscles. Label-free mass spectrometry established altered expression levels for diaphragm proteins associated with contraction, energy metabolism, the cytoskeleton, the extracellular matrix and the cellular stress response. Comparative immunoblotting verified the differences in the degree of secondary changes in dystrophin-deficient muscles and showed that the up-regulation of molecular chaperones, the compensatory increase in proteins of the intermediate filaments, the fibrosis-related increase in collagen levels and the pathophysiological decrease in calcium binding proteins is more pronounced in mdx diaphragm as compared to the less severely affected mdx leg muscles. Annexin, lamin, and vimentin were identified as universal dystrophic markers. Full article
Open AccessArticle Characterization and Pharmacokinetic Study of Aprepitant Solid Dispersions with Soluplus®
Molecules 2015, 20(6), 11345-11356; doi:10.3390/molecules200611345
Received: 27 April 2015 / Revised: 28 May 2015 / Accepted: 1 June 2015 / Published: 19 June 2015
Cited by 8 | PDF Full-text (2236 KB) | HTML Full-text | XML Full-text
Abstract
Solid dispersions are a useful approach to improve the dissolution rate and bioavailability of poorly water-soluble active pharmaceutical ingredients (APIs). The aim of this study was to improve the physicochemical properties and bioavailability of a poorly water-soluble aprepitant by preparation of solid dispersions.
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Solid dispersions are a useful approach to improve the dissolution rate and bioavailability of poorly water-soluble active pharmaceutical ingredients (APIs). The aim of this study was to improve the physicochemical properties and bioavailability of a poorly water-soluble aprepitant by preparation of solid dispersions. The solid dispersions were characterized by dissolution, FTIR, XRPD, DSC, SEM and pharmacokinetic studies in rats. The dissolution rate of the aprepitant was significantly increased by solid dispersions, and XRD, DSC, and SEM analysis indicated that the aprepitant existed in an amorphous form within the solid dispersions. The result of dissolution study showed that the dissolution rate of SDs was nearly five-fold faster than aprepitant. FTIR spectrometry suggested the presence of intermolecular hydrogen bonds between the aprepitant and polymer. Pharmacokinetic studies in rats indicated that the degree drug absorption was comparable with that of Emend®. Aprepitant exists in an amorphous state in solid dispersions and the solid dispersions can markedly improve the dissolution and oral bioavailability of the aprepitant. The AUC0–t of the SDs was 2.4-fold that of the aprepitant. In addition, the method and its associated techniques are very easy to carry out. Full article
(This article belongs to the collection Poorly Soluble Drugs)
Open AccessArticle Individual Constituents from Essential Oils Inhibit Biofilm Mass Production by Multi-Drug Resistant Staphylococcus aureus
Molecules 2015, 20(6), 11357-11372; doi:10.3390/molecules200611357
Received: 6 May 2015 / Revised: 7 June 2015 / Accepted: 16 June 2015 / Published: 19 June 2015
Cited by 11 | PDF Full-text (1011 KB) | HTML Full-text | XML Full-text
Abstract
Biofilm formation by Staphylococcus aureus represents a problem in both the medical field and the food industry, because the biofilm structure provides protection to embedded cells and it strongly attaches to surfaces. This circumstance is leading to many research programs seeking new alternatives
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Biofilm formation by Staphylococcus aureus represents a problem in both the medical field and the food industry, because the biofilm structure provides protection to embedded cells and it strongly attaches to surfaces. This circumstance is leading to many research programs seeking new alternatives to control biofilm formation by this pathogen. In this study we show that a potent inhibition of biofilm mass production can be achieved in community-associated methicillin-resistant S. aureus (CA-MRSA) and methicillin-sensitive strains using plant compounds, such as individual constituents (ICs) of essential oils (carvacrol, citral, and (+)-limonene). The Crystal Violet staining technique was used to evaluate biofilm mass formation during 40 h of incubation. Carvacrol is the most effective IC, abrogating biofilm formation in all strains tested, while CA-MRSA was the most sensitive phenotype to any of the ICs tested. Inhibition of planktonic cells by ICs during initial growth stages could partially explain the inhibition of biofilm formation. Overall, our results show the potential of EOs to prevent biofilm formation, especially in strains that exhibit resistance to other antimicrobials. As these compounds are food additives generally recognized as safe, their anti-biofilm properties may lead to important new applications, such as sanitizers, in the food industry or in clinical settings. Full article
(This article belongs to the Section Natural Products)
Open AccessCommunication Covalently Cross-Linked Arabinoxylans Films for Debaryomyces hansenii Entrapment
Molecules 2015, 20(6), 11373-11386; doi:10.3390/molecules200611373
Received: 30 March 2015 / Revised: 11 June 2015 / Accepted: 12 June 2015 / Published: 19 June 2015
Cited by 5 | PDF Full-text (1980 KB) | HTML Full-text | XML Full-text
Abstract
In the present study, wheat water extractable arabinoxylans (WEAX) were isolated and characterized, and their capability to form covalently cross-linked films in presence of Debaryomyces hansenii was evaluated. WEAX presented an arabinose to xylose ratio of 0.60, a ferulic acid and diferulic acid
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In the present study, wheat water extractable arabinoxylans (WEAX) were isolated and characterized, and their capability to form covalently cross-linked films in presence of Debaryomyces hansenii was evaluated. WEAX presented an arabinose to xylose ratio of 0.60, a ferulic acid and diferulic acid content of 2.1 and 0.04 µg∙mg−1 WEAX, respectively and a Fourier Transform Infra-Red (FT-IR) spectrum typical of WEAX. The intrinsic viscosity and viscosimetric molecular weight values for WEAX were 3.6 dL∙g−1 and 440 kDa, respectively. The gelation of WEAX (1% w/v) with and without D. hansenii (1 × 107 CFU∙cm2) was rheologically investigated by small amplitude oscillatory shear. The entrapment of D. hansenii decreased gel elasticity from 1.4 to 0.3 Pa, probably by affecting the physical interactions between WEAX chains. Covalently cross-linked WEAX films containing D. hansenii were prepared by casting. Scanning electron microscopy images show that WEAX films containing D. hansenii were porous and consisted of granular-like and fibre microstructures. Average tensile strength, elongation at break and Young’s modulus values dropped when D. hansenii was present in the film. Covalently cross-lined WEAX containing D. hansenii could be a suitable as a functional entrapping film. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Xanthones from the Leaves of Garcinia cowa Induce Cell Cycle Arrest, Apoptosis, and Autophagy in Cancer Cells
Molecules 2015, 20(6), 11387-11399; doi:10.3390/molecules200611387
Received: 4 May 2015 / Revised: 14 June 2015 / Accepted: 15 June 2015 / Published: 19 June 2015
Cited by 5 | PDF Full-text (3086 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Two new xanthones, cowaxanthones G (1) and H (2), and 23 known analogues were isolated from an acetone extract of the leaves of Garcinia cowa. The isolated compounds were evaluated for cytotoxicity against three cancer cell lines and
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Two new xanthones, cowaxanthones G (1) and H (2), and 23 known analogues were isolated from an acetone extract of the leaves of Garcinia cowa. The isolated compounds were evaluated for cytotoxicity against three cancer cell lines and immortalized HL7702 normal liver cells, whereby compounds 1, 5, 8, and 1517 exhibited significant cytotoxicity. Cell cycle analysis using flow cytometry showed that 5 induced cell cycle arrest at the S phase in a dose-dependent manner, 1 and 16 at the G2/M phase, and 17 at the G1 phase, while 16 and 17 induced apoptosis. Moreover, autophagy analysis by GFP-LC3 puncta formation and western blotting suggested that 17 induced autophagy. Taken together, our results suggest that these xanthones possess anticancer activities targeting cell cycle, apoptosis, and autophagy signaling pathways. Full article
(This article belongs to the Special Issue Coumarins, Xanthones and Related Compounds)
Open AccessArticle Development of a Large Set of Microsatellite Markers in Zapote Mamey (Pouteria sapota (Jacq.) H.E. Moore & Stearn) and Their Potential Use in the Study of the Species
Molecules 2015, 20(6), 11400-11417; doi:10.3390/molecules200611400
Received: 15 May 2015 / Revised: 16 June 2015 / Accepted: 17 June 2015 / Published: 22 June 2015
Cited by 1 | PDF Full-text (1749 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Pouteria sapota is known for its edible fruits that contain unique carotenoids, as well as for its fungitoxic, anti-inflammatory and anti-oxidant activity. However, its genetics is mostly unknown, including aspects about its genetic diversity and domestication process. We did high-throughput sequencing of microsatellite-enriched
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Pouteria sapota is known for its edible fruits that contain unique carotenoids, as well as for its fungitoxic, anti-inflammatory and anti-oxidant activity. However, its genetics is mostly unknown, including aspects about its genetic diversity and domestication process. We did high-throughput sequencing of microsatellite-enriched libraries of P. sapota, generated 5223 contig DNA sequences, 1.8 Mbp, developed 368 microsatellites markers and tested them on 29 individuals from 10 populations (seven wild, three cultivated) from Mexico, its putative domestication center. Gene ontology BLAST analysis of the DNA sequences containing microsatellites showed potential association to physiological functions. Genetic diversity was slightly higher in cultivated than in the wild gene pool (HE = 0.41 and HE = 0.35, respectively), although modified Garza–Williamson Index and Bottleneck software showed evidence for a reduction in genetic diversity for the cultivated one. Neighbor Joining, 3D Principal Coordinates Analysis and assignment tests grouped most individuals according to their geographic origin but no clear separation was observed between wild or cultivated gene pools due to, perhaps, the existence of several admixed populations. The developed microsatellites have a great potential in genetic population and domestication studies of P. sapota but additional sampling will be necessary to better understand how the domestication process has impacted the genetic diversity of this fruit crop. Full article
(This article belongs to the Section Molecular Diversity)
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Open AccessArticle Synthesis of (E)-2-Styrylchromones and Flavones by Base-Catalyzed Cyclodehydration of the Appropriate β-Diketones Using Water as Solvent
Molecules 2015, 20(6), 11418-11431; doi:10.3390/molecules200611418
Received: 30 April 2015 / Revised: 13 June 2015 / Accepted: 16 June 2015 / Published: 22 June 2015
Cited by 3 | PDF Full-text (790 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A low cost, safe, clean and environmentally benign base-catalyzed cyclodehydration of appropriate β-diketones affording (E)-2-styrylchromones and flavones in good yields is disclosed. Water was used as solvent and the reactions were heated using classical and microwave heating methods, under open and
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A low cost, safe, clean and environmentally benign base-catalyzed cyclodehydration of appropriate β-diketones affording (E)-2-styrylchromones and flavones in good yields is disclosed. Water was used as solvent and the reactions were heated using classical and microwave heating methods, under open and closed vessel conditions. β-Diketones having electron-donating and withdrawing substituents were used to evaluate the reaction scope. The reaction products were isolated in high purity by simple filtration and recrystallization from ethanol, when using 800 mg of the starting diketone under classical reflux heating conditions. Full article
(This article belongs to the Special Issue Frontier in Green Chemistry Approaches)
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Open AccessArticle Characterization of Volatile Compounds of Eleven Achillea Species from Turkey and Biological Activities of Essential Oil and Methanol Extract of A. hamzaoglui Arabacı & Budak
Molecules 2015, 20(6), 11432-11458; doi:10.3390/molecules200611432
Received: 9 April 2015 / Revised: 10 June 2015 / Accepted: 17 June 2015 / Published: 22 June 2015
Cited by 9 | PDF Full-text (1152 KB) | HTML Full-text | XML Full-text
Abstract
According to distribution of genus Achillea, two main centers of diversity occur in S.E. Europe and S.W. Asia. Diversified essential oil compositions from Balkan Peninsula have been numerously reported. However, report on essential oils of Achillea species growing in Turkey, which is
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According to distribution of genus Achillea, two main centers of diversity occur in S.E. Europe and S.W. Asia. Diversified essential oil compositions from Balkan Peninsula have been numerously reported. However, report on essential oils of Achillea species growing in Turkey, which is one of the main centers of diversity, is very limited. This paper represents the chemical compositions of the essential oils obtained by hydrodistillation from the aerial parts of eleven Achillea species, identified simultaneously by gas chromatography and gas chromatography-mass spectrometry. The main components were found to be 1,8-cineole, p-cymene, viridiflorol, nonacosane, α-bisabolol, caryophyllene oxide, α-bisabolon oxide A, β-eudesmol, 15-hexadecanolide and camphor. The chemical principal component analysis based on thirty compounds identified three species groups and a subgroup, where each group constituted a chemotype. This is the first report on the chemical composition of A. hamzaoglui essential oil; as well as the antioxidant and antimicrobial evaluation of its essential oil and methanolic extract. Full article
(This article belongs to the collection Recent Advances in Flavors and Fragrances)
Open AccessArticle Natural Plant Alkaloid (Emetine) Inhibits HIV-1 Replication by Interfering with Reverse Transcriptase Activity
Molecules 2015, 20(6), 11474-11489; doi:10.3390/molecules200611474
Received: 10 May 2015 / Revised: 9 June 2015 / Accepted: 15 June 2015 / Published: 22 June 2015
Cited by 5 | PDF Full-text (1141 KB) | HTML Full-text | XML Full-text
Abstract
Ipecac alkaloids are secondary metabolites produced in the medicinal plant Psychotria ipecacuanha. Emetine is the main alkaloid of ipecac and one of the active compounds in syrup of Ipecac with emetic property. Here we evaluated emetine’s potential as an antiviral agent against
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Ipecac alkaloids are secondary metabolites produced in the medicinal plant Psychotria ipecacuanha. Emetine is the main alkaloid of ipecac and one of the active compounds in syrup of Ipecac with emetic property. Here we evaluated emetine’s potential as an antiviral agent against Human Immunodeficiency Virus. We performed in vitro Reverse Transcriptase (RT) Assay and Natural Endogenous Reverse Transcriptase Activity Assay (NERT) to evaluate HIV RT inhibition. Emetine molecular docking on HIV-1 RT was also analyzed. Phenotypic assays were performed in non-lymphocytic and in Peripheral Blood Mononuclear Cells (PBMC) with HIV-1 wild-type and HIV-harboring RT-resistant mutation to Nucleoside Reverse Transcriptase Inhibitors (M184V). Our results showed that HIV-1 RT was blocked in the presence of emetine in both models: in vitro reactions with isolated HIV-1 RT and intravirion, measured by NERT. Emetine revealed a strong potential of inhibiting HIV-1 replication in both cellular models, reaching 80% of reduction in HIV-1 infection, with low cytotoxic effect. Emetine also blocked HIV-1 infection of RT M184V mutant. These results suggest that emetine is able to penetrate in intact HIV particles, and bind and block reverse transcription reaction, suggesting that it can be used as anti-HIV microbicide. Taken together, our findings provide additional pharmacological information on the potential therapeutic effects of emetine. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Antioxidant Capacities and Analysis of Phenolic Compounds in Three Endemic Nolana Species by HPLC-PDA-ESI-MS
Molecules 2015, 20(6), 11490-11507; doi:10.3390/molecules200611490
Received: 12 May 2015 / Accepted: 17 June 2015 / Published: 22 June 2015
Cited by 12 | PDF Full-text (2651 KB) | HTML Full-text | XML Full-text
Abstract
The antioxidant features, polyphenolic composition and chromatographic fingerprints of the aerial parts from three Chilean endemic plants from the Paposo Valley located on the cost of the Atacama Desert were investigated for the first time using high pressure liquid chromatography coupled with photodiode
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The antioxidant features, polyphenolic composition and chromatographic fingerprints of the aerial parts from three Chilean endemic plants from the Paposo Valley located on the cost of the Atacama Desert were investigated for the first time using high pressure liquid chromatography coupled with photodiode array detector and electrospray ionization mass analysis (HPLC-PDA-ESI-MS) and spectroscopic methods. The phenolic fingerprints obtained for the plants were compared and correlated with the antioxidant capacities measured by the bleaching of the DPPH radical, the ferric reducing antioxidant power (FRAP) and quantification of the total content of phenolics and flavonoids measured by spectroscopic methods. Thirty phenolics were identified for the first time for these species, mostly phenolic acids, flavanones, flavonols and some of their glycoside derivatives, together with three saturated fatty acids (stearic, palmitic and arachidic acids). Nolana ramosissima showed the highest antioxidant activity (26.35 ± 1.02 μg/mL, 116.07 ± 3.42 μM Trolox equivalents/g dry weight and 81.23% ± 3.77% of inhibition in the DPPH, FRAP and scavenging activity (SA) assays, respectively), followed by N. aplocaryoides (85.19 ± 1.64 μg/mL, 65.87 ± 2.33 μM TE/g DW and 53.27% ± 3.07%) and N. leptophylla (124.71 ± 3.01, 44.23 ± 5.18 μM TE/g DW and 38.63% ± 1.85%). Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Ethanolic Extracts of Pluchea indica Induce Apoptosis and Antiproliferation Effects in Human Nasopharyngeal Carcinoma Cells
Molecules 2015, 20(6), 11508-11523; doi:10.3390/molecules200611508
Received: 23 April 2015 / Revised: 10 June 2015 / Accepted: 16 June 2015 / Published: 22 June 2015
PDF Full-text (3694 KB) | HTML Full-text | XML Full-text
Abstract
Pluchea indica is used in traditional medicine for the treatment of lumbago, ulcer, tuberculosis and inflammation. The anti-cancer activities and the underlying molecular mechanisms of the ethanolic extracts of P. indica root (PIRE) were characterized in the present study. PIRE strongly inhibited
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Pluchea indica is used in traditional medicine for the treatment of lumbago, ulcer, tuberculosis and inflammation. The anti-cancer activities and the underlying molecular mechanisms of the ethanolic extracts of P. indica root (PIRE) were characterized in the present study. PIRE strongly inhibited the viability of the human nasopharyngeal carcinoma cells (NPC-TW 01 and NPC-TW 04) in a time- and dose-dependent manner. Migration of cancer cells was also suppressed by PIRE. In addition, PIRE significantly increased the occurrence of the cells in sub-G1 phase and the extent of DNA fragmentation in a dose-dependent manner, which indicates that PIRE significantly increased apoptosis in NPC cells. The apoptotic process triggered by PIRE involved up-regulation of pro-apoptotic Bax protein and down-regulation of anti-apoptotic Bcl-2 protein, consequently increasing the ratios of Bax/Bcl-2 protein levels. Moreover, the p53 protein was up-regulated by PIRE in a concentration-dependent manner. Therefore, PIRE could induce the apoptosis-signaling pathway in NPC cells by activation of p53 and by regulation of apoptosis-related proteins. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Combinational Treatment of Curcumin and Quercetin against Gastric Cancer MGC-803 Cells in Vitro
Molecules 2015, 20(6), 11524-11534; doi:10.3390/molecules200611524
Received: 6 May 2015 / Revised: 31 May 2015 / Accepted: 15 June 2015 / Published: 22 June 2015
Cited by 10 | PDF Full-text (2100 KB) | HTML Full-text | XML Full-text
Abstract
Gastric cancer remains a major health problem worldwide. Natural products, with stronger antitumor activity and fewer side effects, are potential candidates for pharmaceutical development as anticancer agents. In this study, quercetin and curcumin were chosen for testing and were applied separately and in
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Gastric cancer remains a major health problem worldwide. Natural products, with stronger antitumor activity and fewer side effects, are potential candidates for pharmaceutical development as anticancer agents. In this study, quercetin and curcumin were chosen for testing and were applied separately and in combination to human gastric cancer MGC-803 cells. The MTT assay was used to evaluate cell growth inhibition. Annexin V-FITC/PI was carried out to measure apoptosis rate. Flow cytometry was performed to analyze mitochondrial membrane potential levels. Western blots were applied to detect expression of cytochrome c, total and phosphorylated ERK and AKT. Combined treatment with curcumin and quercetin resulted in significant inhibition of cell proliferation, accompanied by loss of mitochondrial membrane potential (ΔΨm), release of cytochrome c and decreased phosphorylation of AKT and ERK. These results indicate that the combination of curcumin and quercetin induces apoptosis through the mitochondrial pathway. Notably, effect of combined treatment with curcumin and quercetin on gastric cancer MGC-803 cells is stronger than that of individual treatment, indicating that curcumin and quercetin combinations have potential as anti-gastric cancer drugs for further development. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Uses of 3-(2-Bromoacetyl)-2H-chromen-2-one in the Synthesis of Heterocyclic Compounds Incorporating Coumarin: Synthesis, Characterization and Cytotoxicity
Molecules 2015, 20(6), 11535-11553; doi:10.3390/molecules200611535
Received: 1 June 2015 / Revised: 17 June 2015 / Accepted: 18 June 2015 / Published: 23 June 2015
Cited by 3 | PDF Full-text (1313 KB) | HTML Full-text | XML Full-text
Abstract
In this work, 3-bromoacetylcoumarin was used as the key starting material for the synthesis of pyran, pyridine, thiophene, thiazole and pyrazole derivatives through its reaction with different reagents. The structures of the newly synthesized compounds were confirmed on the basis of their spectral
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In this work, 3-bromoacetylcoumarin was used as the key starting material for the synthesis of pyran, pyridine, thiophene, thiazole and pyrazole derivatives through its reaction with different reagents. The structures of the newly synthesized compounds were confirmed on the basis of their spectral data and elemental analyses. All of the synthesized compounds were screened for their in vitro anticancer activity against six human cancer cell lines, namely: human gastric cancer (NUGC), human colon cancer (DLD1), human liver cancer (HA22T and HEPG2), nasopharyngeal carcinoma (HONE1), human breast cancer (MCF) and normal fibroblast cells (WI38). The IC50 values (the sample concentration that produces 50% reduction in cell growth) in nanomolars (nM)) showed most of the compounds exhibited significant cytotoxic effect. Among these derivatives, compound 6d showed almost equipotent cytotoxic activity against NUGC (IC50 = 29 nM) compared to the standard CHS 828 (IC50 = 25 nM). Full article
(This article belongs to the collection Heterocyclic Compounds)
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Open AccessArticle Trypanocidal Activity of Long Chain Diamines and Aminoalcohols
Molecules 2015, 20(6), 11554-11568; doi:10.3390/molecules200611554
Received: 15 April 2015 / Revised: 16 June 2015 / Accepted: 17 June 2015 / Published: 23 June 2015
Cited by 3 | PDF Full-text (728 KB) | HTML Full-text | XML Full-text
Abstract
Thirteen aminoalcohols and eight diamines were obtained and tested against Trypanosoma cruzi epimastigotes strains MG, JEM and CL-B5 clone. Some of them were equal or more potent (1.0–6.6 times) than the reference compound nifurtimox. From them, three aminoalcohols and two diamines were selected
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Thirteen aminoalcohols and eight diamines were obtained and tested against Trypanosoma cruzi epimastigotes strains MG, JEM and CL-B5 clone. Some of them were equal or more potent (1.0–6.6 times) than the reference compound nifurtimox. From them, three aminoalcohols and two diamines were selected for amastigotes assays. Compound 5 was as potent as the reference drug nifurtimox against amastigotes of the CL-B5 strain (IC50 = 0.6 µM), with a selectivity index of 54. Full article
(This article belongs to the Special Issue Antiparasitic Agents)
Open AccessArticle Protective Effects of Korean Red Ginseng against Alcohol-Induced Fatty Liver in Rats
Molecules 2015, 20(6), 11604-11616; doi:10.3390/molecules200611604
Received: 27 April 2015 / Revised: 15 June 2015 / Accepted: 16 June 2015 / Published: 23 June 2015
Cited by 2 | PDF Full-text (2371 KB) | HTML Full-text | XML Full-text
Abstract
The present study tested the hypothesis that Korean red ginseng (KRG) provides a protective effect against alcoholic fatty liver. Male Sprague-Dawley rats were divided into four groups and fed a modified Lieber-DeCarli diet containing 5% (w/v) alcohol or an
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The present study tested the hypothesis that Korean red ginseng (KRG) provides a protective effect against alcoholic fatty liver. Male Sprague-Dawley rats were divided into four groups and fed a modified Lieber-DeCarli diet containing 5% (w/v) alcohol or an isocaloric amount of dextrin-maltose for the controls for 6 weeks: normal control (CON), alcohol control (ET), and ET treated with 125 or 250 mg/kg body weight/day of KRG (RGL or RGH, respectively). Compared with the CON group, the ET group exhibited a significant increase in triglycerides, total cholesterol and the presence of lipid droplets in the liver, and a decrease in fat mass, which were all attenuated by KRG supplementation in adose-dependent manner. The mitigation was accompanied by AMP-activated protein kinase (AMPK) signaling pathways in the liver and adipose tissue. In addition, suppression in the alcohol-induced changes of adipose adipokine mRNA expression was also observed in KRG supplementation group. These findings suggest that KRG may have the potential to ameliorate alcoholic fatty liver by suppressing inappropriate lysis of adipose tissue and preventing unnecessary de novo lipogenesis in the liver, which are mediated by AMPK signaling pathways. A mechanism for an interplay between the two organs is still needed to be examined with further assays. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Microwave-Assisted Condensation Reactions of Acetophenone Derivatives and Activated Methylene Compounds with Aldehydes Catalyzed by Boric Acid under Solvent-Free Conditions
Molecules 2015, 20(6), 11617-11631; doi:10.3390/molecules200611617
Received: 28 May 2015 / Revised: 14 June 2015 / Accepted: 15 June 2015 / Published: 23 June 2015
Cited by 3 | PDF Full-text (794 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
We here disclosed a new protocol for the condensation of acetophenone derivatives and active methylene compounds with aldehydes in the presence of boric acid under microwave conditions. Implementation of the reaction is simple, healthy and environmentally friendly owing to the use of a
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We here disclosed a new protocol for the condensation of acetophenone derivatives and active methylene compounds with aldehydes in the presence of boric acid under microwave conditions. Implementation of the reaction is simple, healthy and environmentally friendly owing to the use of a non-toxic catalyst coupled to a solvent-free procedure. A large variety of known or novel compounds have thus been prepared, including with substrates bearing acid or base-sensitive functional groups. Full article
(This article belongs to the Special Issue Microwave-Assisted Organic Synthesis)

Review

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Open AccessReview Multifunctional Iron Bound Lactoferrin and Nanomedicinal Approaches to Enhance Its Bioactive Functions
Molecules 2015, 20(6), 9703-9731; doi:10.3390/molecules20069703
Received: 23 February 2015 / Accepted: 13 May 2015 / Published: 26 May 2015
Cited by 18 | PDF Full-text (1616 KB) | HTML Full-text | XML Full-text
Abstract
Lactoferrin (Lf), an iron-binding protein from the transferrin family has been reported to have numerous functions. Even though Lf was first isolated from milk, it is also found in most exocrine secretions and in the secondary granules of neutrophils. Antimicrobial and anti-inflammatory activity
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Lactoferrin (Lf), an iron-binding protein from the transferrin family has been reported to have numerous functions. Even though Lf was first isolated from milk, it is also found in most exocrine secretions and in the secondary granules of neutrophils. Antimicrobial and anti-inflammatory activity reports on lactoferrin identified its significance in host defense against infection and extreme inflammation. Anticarcinogenic reports on lactoferrin make this protein even more valuable. This review is focused on the structural configuration of iron-containing and iron-free forms of lactoferrin obtained from different sources such as goat, camel and bovine. Apart for emphasizing on the specific beneficial properties of lactoferrin from each of these sources, the general antimicrobial, immunomodulatory and anticancer activities of lactoferrin are discussed here. Implementation of nanomedicinial strategies that enhance the bioactive function of lactoferrin are also discussed, along with information on lactoferrin in clinical trials. Full article
(This article belongs to the collection Nanomedicine)
Open AccessReview Molecular Interactions of β-(1→3)-Glucans with Their Receptors
Molecules 2015, 20(6), 9745-9766; doi:10.3390/molecules20069745
Received: 14 April 2015 / Accepted: 20 May 2015 / Published: 27 May 2015
Cited by 14 | PDF Full-text (1539 KB) | HTML Full-text | XML Full-text
Abstract
β-(1→3)-Glucans can be found as structural polysaccharides in cereals, in algae or as exo-polysaccharides secreted on the surfaces of mushrooms or fungi. Research has now established that β-(1→3)-glucans can trigger different immune responses and act as efficient immunostimulating agents. They constitute prevalent sources
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β-(1→3)-Glucans can be found as structural polysaccharides in cereals, in algae or as exo-polysaccharides secreted on the surfaces of mushrooms or fungi. Research has now established that β-(1→3)-glucans can trigger different immune responses and act as efficient immunostimulating agents. They constitute prevalent sources of carbons for microorganisms after subsequent recognition by digesting enzymes. Nevertheless, mechanisms associated with both roles are not yet clearly understood. This review focuses on the variety of elucidated molecular interactions that involve these natural or synthetic polysaccharides and their receptors, i.e., Dectin-1, CR3, glycolipids, langerin and carbohydrate-binding modules. Full article
(This article belongs to the Special Issue Protein-Carbohydrate Interactions, and Beyond)
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Open AccessReview The Role of Lectin-Carbohydrate Interactions in the Regulation of ER-Associated Protein Degradation
Molecules 2015, 20(6), 9816-9846; doi:10.3390/molecules20069816
Received: 28 April 2015 / Revised: 20 May 2015 / Accepted: 21 May 2015 / Published: 27 May 2015
Cited by 9 | PDF Full-text (1353 KB) | HTML Full-text | XML Full-text
Abstract
Proteins entering the secretory pathway are translocated across the endoplasmic reticulum (ER) membrane in an unfolded form. In the ER they are restricted to a quality control system that ensures correct folding or eventual degradation of improperly folded polypeptides. Mannose trimming of N-
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Proteins entering the secretory pathway are translocated across the endoplasmic reticulum (ER) membrane in an unfolded form. In the ER they are restricted to a quality control system that ensures correct folding or eventual degradation of improperly folded polypeptides. Mannose trimming of N-glycans on newly synthesized proteins plays an important role in the recognition and sorting of terminally misfolded glycoproteins for ER-associated protein degradation (ERAD). In this process misfolded proteins are retrotranslocated into the cytosol, polyubiquitinated, and eventually degraded by the proteasome. The mechanism by which misfolded glycoproteins are recognized and recruited to the degradation machinery has been extensively studied during last decade. In this review, we focus on ER degradation-enhancing α-mannosidase-like protein (EDEM) family proteins that seem to play a key role in the discrimination between proteins undergoing a folding process and terminally misfolded proteins directed for degradation. We describe interactions of EDEM proteins with other components of the ERAD machinery, as well as with various protein substrates. Carbohydrate-dependent interactions together with N-glycan-independent interactions seem to regulate the complex process of protein recognition and direction for proteosomal degradation. Full article
(This article belongs to the Special Issue Protein-Carbohydrate Interactions, and Beyond)
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Open AccessReview Developments in Synthetic Application of Selenium(IV) Oxide and Organoselenium Compounds as Oxygen Donors and Oxygen-Transfer Agents
Molecules 2015, 20(6), 10205-10243; doi:10.3390/molecules200610205
Received: 31 March 2015 / Revised: 23 May 2015 / Accepted: 1 June 2015 / Published: 3 June 2015
Cited by 20 | PDF Full-text (891 KB) | HTML Full-text | XML Full-text
Abstract
A variety of selenium compounds were proven to be useful reagents and catalysts for organic synthesis over the past several decades. The most interesting aspect, which emerged in recent years, concerns application of hydroperoxide/selenium(IV) oxide and hydroperoxide/organoselenium catalyst systems, as “green reagents” for
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A variety of selenium compounds were proven to be useful reagents and catalysts for organic synthesis over the past several decades. The most interesting aspect, which emerged in recent years, concerns application of hydroperoxide/selenium(IV) oxide and hydroperoxide/organoselenium catalyst systems, as “green reagents” for the oxidation of different organic functional groups. The topic of oxidations catalyzed by organoselenium derivatives has rapidly expanded in the last fifteen years This paper is devoted to the synthetic applications of the oxidation reactions mediated by selenium compounds such as selenium(IV) oxide, areneseleninic acids, their anhydrides, selenides, diselenides, benzisoselenazol-3(2H)-ones and other less often used other organoselenium compounds. All these compounds have been successfully applied for various oxidations useful in practical organic syntheses such as epoxidation, 1,2-dihydroxylation, and α-oxyfunctionalization of alkenes, as well as for ring contraction of cycloalkanones, conversion of halomethyl, hydroxymethyl or active methylene groups into formyl groups, oxidation of carbonyl compounds into carboxylic acids and/or lactones, sulfides into sulfoxides, and secondary amines into nitrones and regeneration of parent carbonyl compounds from their azomethine derivatives. Other reactions such as dehydrogenation and aromatization, active carbon-carbon bond cleavage, oxidative amidation, bromolactonization and oxidation of bromide for subsequent reactions with alkenes are also successfully mediated by selenium (IV) oxide or organoselenium compounds. The oxidation mechanisms of ionic or free radical character depending on the substrate and oxidant are discussed. Coverage of the literature up to early 2015 is provided. Links have been made to reviews that summarize earlier literature and to the methods of preparation of organoselenium reagents and catalysts. Full article
(This article belongs to the Special Issue Selenium Catalysts and Antioxidants)
Open AccessReview Overview of Methods for the Direct Molar Mass Determination of Cellulose
Molecules 2015, 20(6), 10313-10341; doi:10.3390/molecules200610313
Received: 10 March 2015 / Revised: 6 May 2015 / Accepted: 27 May 2015 / Published: 4 June 2015
Cited by 12 | PDF Full-text (946 KB) | HTML Full-text | XML Full-text
Abstract
The purpose of this article is to provide the reader with an overview of the methods used to determine the molecular weights of cellulose. Methods that employ direct dissolution of the cellulose polymer are described; hence methods for investigating the molecular weight of
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The purpose of this article is to provide the reader with an overview of the methods used to determine the molecular weights of cellulose. Methods that employ direct dissolution of the cellulose polymer are described; hence methods for investigating the molecular weight of cellulose in derivatized states, such as ethers or esters, only form a minor part of this review. Many of the methods described are primarily of historical interest since they have no use in modern cellulose chemistry. However, older methods, such as osmometry or ultracentrifuge experiments, were the first analytical methods used in polymer chemistry and continue to serve as sources of fundamental information (such as the cellulose structure in solution). The first part of the paper reviews methods, either absolute or relative, for the estimation of average molecular weights. Regardless of an absolute or relative approach, the outcome is a molecular weight average (MWA). In the final section, coupling methods are described. The primary benefit of performing a pre-separation step on the molecules is the discovery of the molecular weight distribution (MWD). Here, size exclusion chromatography (SEC) is unquestionably the most powerful and most commonly-applied method in modern laboratories and industrial settings. Full article
(This article belongs to the Special Issue New Trends in Cellulose and Chitin Chemistry)
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Open AccessReview Non-Conventional Yeasts Whole Cells as Efficient Biocatalysts for the Production of Flavors and Fragrances
Molecules 2015, 20(6), 10377-10398; doi:10.3390/molecules200610377
Received: 12 May 2015 / Revised: 31 May 2015 / Accepted: 1 June 2015 / Published: 4 June 2015
Cited by 5 | PDF Full-text (766 KB) | HTML Full-text | XML Full-text
Abstract
The rising consumer requests for natural flavors and fragrances have generated great interest in the aroma industry to seek new methods to obtain fragrance and flavor compounds naturally. An alternative and attractive route for these compounds is based on bio-transformations. In this review,
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The rising consumer requests for natural flavors and fragrances have generated great interest in the aroma industry to seek new methods to obtain fragrance and flavor compounds naturally. An alternative and attractive route for these compounds is based on bio-transformations. In this review, the application of biocatalysis by Non Conventional Yeasts (NCYs) whole cells for the production of flavor and fragrances is illustrated by a discussion of the production of different class of compounds, namely Aldehydes, Ketones and related compounds, Alcohols, Lactones, Terpenes and Terpenoids, Alkenes, and Phenols. Full article
(This article belongs to the collection Recent Advances in Flavors and Fragrances)
Open AccessReview Role and Regulation of Glutathione Metabolism in Plasmodium falciparum
Molecules 2015, 20(6), 10511-10534; doi:10.3390/molecules200610511
Received: 10 April 2015 / Revised: 11 May 2015 / Accepted: 1 June 2015 / Published: 8 June 2015
Cited by 14 | PDF Full-text (831 KB) | HTML Full-text | XML Full-text
Abstract
Malaria in humans is caused by one of five species of obligate intracellular protozoan parasites of the genus Plasmodium. P. falciparum causes the most severe disease and is responsible for 600,000 deaths annually, primarily in Sub-Saharan Africa. It has long been suggested that
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Malaria in humans is caused by one of five species of obligate intracellular protozoan parasites of the genus Plasmodium. P. falciparum causes the most severe disease and is responsible for 600,000 deaths annually, primarily in Sub-Saharan Africa. It has long been suggested that during their development, malaria parasites are exposed to environmental and metabolic stresses. One strategy to drug discovery was to increase these stresses by interfering with the parasites’ antioxidant and redox systems, which may be a valuable approach to disease intervention. Plasmodium possesses two redox systems—the thioredoxin and the glutathione system—with overlapping but also distinct functions. Glutathione is the most abundant low molecular weight redox active thiol in the parasites existing primarily in its reduced form representing an excellent thiol redox buffer. This allows for an efficient maintenance of the intracellular reducing environment of the parasite cytoplasm and its organelles. This review will highlight the mechanisms that are responsible for sustaining an adequate concentration of glutathione and maintaining its redox state in Plasmodium. It will provide a summary of the functions of the tripeptide and will discuss the potential of glutathione metabolism for drug discovery against human malaria parasites. Full article
(This article belongs to the Special Issue Thioredoxin and Glutathione Systems)
Open AccessReview Mucin-Type O-Glycosylation in Invertebrates
Molecules 2015, 20(6), 10622-10640; doi:10.3390/molecules200610622
Received: 14 March 2015 / Revised: 1 June 2015 / Accepted: 3 June 2015 / Published: 9 June 2015
Cited by 5 | PDF Full-text (892 KB) | HTML Full-text | XML Full-text
Abstract
O-Glycosylation is one of the most important posttranslational modifications of proteins. It takes part in protein conformation, protein sorting, developmental processes and the modulation of enzymatic activities. In vertebrates, the basics of the biosynthetic pathway of O-glycans are already well understood.
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O-Glycosylation is one of the most important posttranslational modifications of proteins. It takes part in protein conformation, protein sorting, developmental processes and the modulation of enzymatic activities. In vertebrates, the basics of the biosynthetic pathway of O-glycans are already well understood. However, the regulation of the processes and the molecular aspects of defects, especially in correlation with cancer or developmental abnormalities, are still under investigation. The knowledge of the correlating invertebrate systems and evolutionary aspects of these highly conserved biosynthetic events may help improve the understanding of the regulatory factors of this pathway. Invertebrates display a broad spectrum of glycosylation varieties, providing an enormous potential for glycan modifications which may be used for the design of new pharmaceutically active substances. Here, overviews of the present knowledge of invertebrate mucin-type O-glycan structures and the currently identified enzymes responsible for the biosynthesis of these oligosaccharides are presented, and the few data dealing with functional aspects of O-glycans are summarised. Full article
(This article belongs to the Special Issue Protein-Carbohydrate Interactions, and Beyond)
Open AccessReview Neurotrophins and Neuropathic Pain: Role in Pathobiology
Molecules 2015, 20(6), 10657-10688; doi:10.3390/molecules200610657
Received: 21 April 2015 / Accepted: 3 June 2015 / Published: 9 June 2015
Cited by 28 | PDF Full-text (1299 KB) | HTML Full-text | XML Full-text
Abstract
Neurotrophins (NTs) belong to a family of trophic factors that regulate the survival, growth and programmed cell death of neurons. In mammals, there are four structurally and functionally related NT proteins, viz. nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin 3
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Neurotrophins (NTs) belong to a family of trophic factors that regulate the survival, growth and programmed cell death of neurons. In mammals, there are four structurally and functionally related NT proteins, viz. nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin 3 and neurotrophin 4. Most research on NTs to date has focussed on the effects of NGF and BDNF signalling via their respective cognate high affinity neurotrophic tyrosine kinase viz TrkA and TrkB receptors. Apart from the key physiologic roles of NGF and BDNF in peripheral and central nervous system function, NGF and BDNF signalling via TrkA and TrkB receptors respectively have been implicated in mechanisms underpinning neuropathic pain. Additionally, NGF and BDNF signalling via the low-affinity pan neurotrophin receptor at 75 kDa (p75NTR) may also contribute to the pathobiology of neuropathic pain. In this review, we critically assess the role of neurotrophins signalling via their cognate high affinity receptors as well as the low affinity p75NTR in the pathophysiology of peripheral neuropathic and central neuropathic pain. We also identify knowledge gaps to guide future research aimed at generating novel insight on how to optimally modulate NT signalling for discovery of novel therapeutics to improve neuropathic pain relief. Full article
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Open AccessReview Carbocations and the Complex Flavor and Bouquet of Wine: Mechanistic Aspects of Terpene Biosynthesis in Wine Grapes
Molecules 2015, 20(6), 10781-10792; doi:10.3390/molecules200610781
Received: 16 March 2015 / Revised: 29 May 2015 / Accepted: 8 June 2015 / Published: 11 June 2015
Cited by 5 | PDF Full-text (789 KB) | HTML Full-text | XML Full-text
Abstract
Computational chemistry approaches for studying the formation of terpenes/terpenoids in wines are presented, using five particular terpenes/terpenoids (1,8-cineole, α-ylangene, botrydial, rotundone, and the wine lactone), volatile compounds (or their precursors) found in wine and/or wine grapes, as representative examples. Through these examples, we
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Computational chemistry approaches for studying the formation of terpenes/terpenoids in wines are presented, using five particular terpenes/terpenoids (1,8-cineole, α-ylangene, botrydial, rotundone, and the wine lactone), volatile compounds (or their precursors) found in wine and/or wine grapes, as representative examples. Through these examples, we show how modern computational quantum chemistry can be employed as an effective tool for assessing the validity of proposed mechanisms for terpene/terpenoid formation. Full article
(This article belongs to the collection Wine Chemistry)
Open AccessReview Progress in Studies on Rutaecarpine. II.—Synthesis and Structure-Biological Activity Relationships
Molecules 2015, 20(6), 10800-10821; doi:10.3390/molecules200610800
Received: 14 May 2015 / Revised: 27 May 2015 / Accepted: 1 June 2015 / Published: 11 June 2015
Cited by 7 | PDF Full-text (1006 KB) | HTML Full-text | XML Full-text
Abstract
Rutaecarpine is a pentacyclic indolopyridoquinazolinone alkaloid found in Evodia rutaecarpa and other related herbs. It has a variety of intriguing biological properties, which continue to attract the academic and industrial interest. Studies on rutaecarpine have included isolation from new natural sources, development of
[...] Read more.
Rutaecarpine is a pentacyclic indolopyridoquinazolinone alkaloid found in Evodia rutaecarpa and other related herbs. It has a variety of intriguing biological properties, which continue to attract the academic and industrial interest. Studies on rutaecarpine have included isolation from new natural sources, development of new synthetic methods for its total synthesis, the discovery of new biological activities, metabolism, toxicology, and establishment of analytical methods for determining rutaecarpine content. The present review focuses on the synthesis, biological activities, and structure-activity relationships of rutaecarpine derivatives, with respect to their antiplatelet, vasodilatory, cytotoxic, and anticholinesterase activities. Full article
Open AccessReview A Review of Extraction and Analysis of Bioactives in Oat and Barley and Scope for Use of Novel Food Processing Technologies
Molecules 2015, 20(6), 10884-10909; doi:10.3390/molecules200610884
Received: 7 April 2015 / Revised: 25 May 2015 / Accepted: 5 June 2015 / Published: 12 June 2015
Cited by 14 | PDF Full-text (806 KB) | HTML Full-text | XML Full-text
Abstract
Oat and barely are cereal crops mainly used as animal feed and for the purposes of malting and brewing, respectively. Some studies have indicated that consumption of oat and barley rich foods may reduce the risk of some chronic diseases such as coronary
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Oat and barely are cereal crops mainly used as animal feed and for the purposes of malting and brewing, respectively. Some studies have indicated that consumption of oat and barley rich foods may reduce the risk of some chronic diseases such as coronary heart disease, type II diabetes and cancer. Whilst there is no absolute consensus, some of these benefits may be linked to presence of compounds such as phenolics, vitamin E and β-glucan in these cereals. A number of benefits have also been linked to the lipid component (sterols, fatty acids) and the proteins and bioactive peptides in oats and barley. Since the available evidence is pointing toward the possible health benefits of oat and barley components, a number of authors have examined techniques for recovering them from their native sources. In the present review, we summarise and examine the range of conventional techniques that have been used for the purpose of extraction and detection of these bioactives. In addition, the recent advances in use of novel food processing technologies as a substitute to conventional processes for extraction of bioactives from oats and barley, has been discussed. Full article
(This article belongs to the Special Issue New Technologies for the Recovery of Natural Products)
Open AccessReview Green Chemistry Metrics with Special Reference to Green Analytical Chemistry
Molecules 2015, 20(6), 10928-10946; doi:10.3390/molecules200610928
Received: 25 April 2015 / Revised: 2 June 2015 / Accepted: 9 June 2015 / Published: 12 June 2015
Cited by 15 | PDF Full-text (1263 KB) | HTML Full-text | XML Full-text
Abstract
The concept of green chemistry is widely recognized in chemical laboratories. To properly measure an environmental impact of chemical processes, dedicated assessment tools are required. This paper summarizes the current state of knowledge in the field of development of green chemistry and green
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The concept of green chemistry is widely recognized in chemical laboratories. To properly measure an environmental impact of chemical processes, dedicated assessment tools are required. This paper summarizes the current state of knowledge in the field of development of green chemistry and green analytical chemistry metrics. The diverse methods used for evaluation of the greenness of organic synthesis, such as eco-footprint, E-Factor, EATOS, and Eco-Scale are described. Both the well-established and recently developed green analytical chemistry metrics, including NEMI labeling and analytical Eco-scale, are presented. Additionally, this paper focuses on the possibility of the use of multivariate statistics in evaluation of environmental impact of analytical procedures. All the above metrics are compared and discussed in terms of their advantages and disadvantages. The current needs and future perspectives in green chemistry metrics are also discussed. Full article
(This article belongs to the Special Issue Frontier in Green Chemistry Approaches)
Open AccessReview Development of Orally Active Thrombin Inhibitors for the Treatment of Thrombotic Disorder Diseases
Molecules 2015, 20(6), 11046-11062; doi:10.3390/molecules200611046
Received: 14 May 2015 / Accepted: 10 June 2015 / Published: 15 June 2015
Cited by 3 | PDF Full-text (916 KB) | HTML Full-text | XML Full-text
Abstract
Thrombotic disorders represent the major share of the various cardiovascular diseases, and significant progress has been made in the development of synthetic thrombin inhibitors as new anticoagulants. In addition to the development of highly potent and selective inhibitors with improved safety and suitable
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Thrombotic disorders represent the major share of the various cardiovascular diseases, and significant progress has been made in the development of synthetic thrombin inhibitors as new anticoagulants. In addition to the development of highly potent and selective inhibitors with improved safety and suitable half-life, several allosteric inhibitors have been designed and synthesized, that did not fully nullify the procoagulant signal and thus could result in reduced bleeding complications. Furthermore, natural products with thrombin inhibitory activity have been isolated, and some natural products have been modified in order to improve their inhibitory activity and metabolic stability. This review summarizes the development of orally active thrombin inhibitors for the treatment of thrombotic disorder diseases, which could serve as a reference for the interested researchers. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessReview Plasmodium falciparum Thioredoxin Reductase (PfTrxR) and Its Role as a Target for New Antimalarial Discovery
Molecules 2015, 20(6), 11459-11473; doi:10.3390/molecules200611459
Received: 12 May 2015 / Revised: 12 June 2015 / Accepted: 17 June 2015 / Published: 22 June 2015
Cited by 5 | PDF Full-text (1021 KB) | HTML Full-text | XML Full-text
Abstract
The growing resistance to current antimalarial drugs is a major concern for global public health. The pressing need for new antimalarials has led to an increase in research focused on the Plasmodium parasites that cause human malaria. Thioredoxin reductase (TrxR), an enzyme needed
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The growing resistance to current antimalarial drugs is a major concern for global public health. The pressing need for new antimalarials has led to an increase in research focused on the Plasmodium parasites that cause human malaria. Thioredoxin reductase (TrxR), an enzyme needed to maintain redox equilibrium in Plasmodium species, is a promising target for new antimalarials. This review paper provides an overview of the structure and function of TrxR, discusses similarities and differences between the thioredoxin reductases (TrxRs) of different Plasmodium species and the human forms of the enzyme, gives an overview of modeling Plasmodium infections in animals, and suggests the role of Trx functions in antimalarial drug resistance. TrxR of Plasmodium falciparum is a central focus of this paper since it is the only Plasmodium TrxR that has been crystallized and P. falciparum is the species that causes most malaria cases. It is anticipated that the information summarized here will give insight and stimulate new directions in which research might be most beneficial. Full article
(This article belongs to the Special Issue Thioredoxin and Glutathione Systems)
Open AccessReview Surfing the Protein-Protein Interaction Surface Using Docking Methods: Application to the Design of PPI Inhibitors
Molecules 2015, 20(6), 11569-11603; doi:10.3390/molecules200611569
Received: 27 March 2015 / Revised: 2 June 2015 / Accepted: 15 June 2015 / Published: 23 June 2015
Cited by 5 | PDF Full-text (2526 KB) | HTML Full-text | XML Full-text
Abstract
Blocking protein-protein interactions (PPI) using small molecules or peptides modulates biochemical pathways and has therapeutic significance. PPI inhibition for designing drug-like molecules is a new area that has been explored extensively during the last decade. Considering the number of available PPI inhibitor databases
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Blocking protein-protein interactions (PPI) using small molecules or peptides modulates biochemical pathways and has therapeutic significance. PPI inhibition for designing drug-like molecules is a new area that has been explored extensively during the last decade. Considering the number of available PPI inhibitor databases and the limited number of 3D structures available for proteins, docking and scoring methods play a major role in designing PPI inhibitors as well as stabilizers. Docking methods are used in the design of PPI inhibitors at several stages of finding a lead compound, including modeling the protein complex, screening for hot spots on the protein-protein interaction interface and screening small molecules or peptides that bind to the PPI interface. There are three major challenges to the use of docking on the relatively flat surfaces of PPI. In this review we will provide some examples of the use of docking in PPI inhibitor design as well as its limitations. The combination of experimental and docking methods with improved scoring function has thus far resulted in few success stories of PPI inhibitors for therapeutic purposes. Docking algorithms used for PPI are in the early stages, however, and as more data are available docking will become a highly promising area in the design of PPI inhibitors or stabilizers. Full article
(This article belongs to the Special Issue Molecular Docking in Drug Design)
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