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Molecules, Volume 20, Issue 10 (October 2015) , Pages 17684-19646

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Open AccessArticle Hinokitiol Exerts Anticancer Activity through Downregulation of MMPs 9/2 and Enhancement of Catalase and SOD Enzymes: In Vivo Augmentation of Lung Histoarchitecture
Molecules 2015, 20(10), 17720-17734; https://doi.org/10.3390/molecules201017720
Received: 21 August 2015 / Revised: 18 September 2015 / Accepted: 22 September 2015 / Published: 25 September 2015
Cited by 8 | Viewed by 2382 | PDF Full-text (1343 KB) | HTML Full-text | XML Full-text
Abstract
Melanoma is extremely resistant to chemotherapy and the death rate is increasing hastily worldwide. Extracellular matrix promotes the migration and invasion of tumor cells through the production of matrix metalloproteinase (MMP)-2 and -9. Evidence has shown that natural dietary antioxidants are capable of [...] Read more.
Melanoma is extremely resistant to chemotherapy and the death rate is increasing hastily worldwide. Extracellular matrix promotes the migration and invasion of tumor cells through the production of matrix metalloproteinase (MMP)-2 and -9. Evidence has shown that natural dietary antioxidants are capable of inhibiting cancer cell growth. Our recent studies showed that hinokitiol, a natural bioactive compound, inhibited vascular smooth muscle cell proliferation and platelets aggregation. The present study is to investigate the anticancer efficacy of hinokitiol against B16-F10 melanoma cells via modulating tumor invasion factors MMPs, antioxidant enzymes in vitro. An in vivo mice model of histological investigation was performed to study the patterns of elastic and collagen fibers. Hinokitiol inhibited the expression and activity of MMPs-2 and -9 in B16-F10 melanoma cells, as measured by western blotting and gelatin zymography, respectively. An observed increase in protein expression of MMPs 2/9 in melanoma cells was significantly inhibited by hinokitiol. Notably, hinokitiol (1–5 μM) increased the activities of antioxidant enzymes catalase (CAT) and superoxide dismutase (SOD) from the reduction in melanoma cells. Also, hinokitiol (2–10 µM) concentration dependently reduced in vitro Fenton reaction induced hydroxyl radical (OH·) formation. An in vivo study showed that hinokitiol treatment increased elastic fibers (EF), collagens dispersion, and improved alveolar alterations in the lungs of B16/F10 injected mice. Overall, our findings propose that hinokitiol may be a potent anticancer candidate through down regulation of MMPs 9/2, reduction of OH· production and enhancement of antioxidant enzymes SOD and CAT. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessCommunication Identification of Minor Benzoylated 4-Phenylcoumarins from a Mammea neurophylla Bark Extract
Molecules 2015, 20(10), 17735-17746; https://doi.org/10.3390/molecules201017735
Received: 7 July 2015 / Revised: 25 August 2015 / Accepted: 17 September 2015 / Published: 25 September 2015
Cited by 3 | Viewed by 2011 | PDF Full-text (764 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Through dereplication analysis, seven known Mammea coumarins were identified in a fraction obtained from Mammea neurophylla dichloromethane bark extract selected for its ability to prevent advanced glycation end-product (AGE) formation. Among them, a careful examination of the NMR dataset of pedilanthocoumarin B led [...] Read more.
Through dereplication analysis, seven known Mammea coumarins were identified in a fraction obtained from Mammea neurophylla dichloromethane bark extract selected for its ability to prevent advanced glycation end-product (AGE) formation. Among them, a careful examination of the NMR dataset of pedilanthocoumarin B led to a structural revision. Inspection of LC-DAD-MSn chromatograms allowed us to predict the presence of four new compounds, which were further isolated. Using spectroscopic methods (1H-, 13C- and 2D-NMR, HRMS, UV), these compounds were identified as new benzoyl substituted 4-phenylcoumarins (iso-pedilanthocoumarin B and neurophyllol C) and 4-(1-acetoxypropyl)coumarins cyclo F (ochrocarpins H and I). Full article
(This article belongs to the Special Issue Coumarins, Xanthones and Related Compounds)
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Open AccessArticle Protective Effect of Plantago major Extract against t-BOOH-Induced Mitochondrial Oxidative Damage and Cytotoxicity
Molecules 2015, 20(10), 17747-17759; https://doi.org/10.3390/molecules201017747
Received: 10 August 2015 / Revised: 18 September 2015 / Accepted: 21 September 2015 / Published: 25 September 2015
Cited by 4 | Viewed by 2289 | PDF Full-text (1425 KB) | HTML Full-text | XML Full-text
Abstract
Plantago major L. produces several chemical substances with anti-inflammatory and analgesic activities and its use in the treatment of oral and throat inflammation in popular medicine is well described. In this study, the antioxidant potential of the Plantago major hydroethanolic extract was screened [...] Read more.
Plantago major L. produces several chemical substances with anti-inflammatory and analgesic activities and its use in the treatment of oral and throat inflammation in popular medicine is well described. In this study, the antioxidant potential of the Plantago major hydroethanolic extract was screened and its protective action was evaluated against t-BOOH-induced oxidative stress. The extract was obtained by fractionated percolation using 50% ethanolic solution and, after drying, suspended in dimethyl sulfoxide. The chromatographic profile of crude extract was obtained with the identification of some phytochemical markers and the total phenols and flavonoids were quantified. The scavenger activity against DPPH (1,1-diphenyl-2-picrylhydrazyl) radicals was determined and the antioxidant activity in biological systems was evaluated in isolated rat liver mitochondria and HepG2 cells. The extract exhibited a significant free radical scavenger activity at 0.1 mg/mL, and decreased the ROS (reactive oxygen species) generation in succinate-energized mitochondria. Such an effect was associated with the preservation of the intrinsic antioxidant defenses (reduced glutathione and NAD(P)H) against the oxidation by t-BOOH, and also to the protection of membranes from lipid oxidation. The cytoprotective effect of PmHE against t-BOOH induced cell death was also shown. These findings contribute to the understanding of the health benefits attributed to P. major. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Enhanced Bioaccessibility of Crocetin Sugar Esters from Saffron in Infusions Rich in Natural Phenolic Antioxidants
Molecules 2015, 20(10), 17760-17774; https://doi.org/10.3390/molecules201017760
Received: 25 August 2015 / Revised: 15 September 2015 / Accepted: 21 September 2015 / Published: 25 September 2015
Cited by 9 | Viewed by 2197 | PDF Full-text (792 KB) | HTML Full-text | XML Full-text
Abstract
The present study aims to examine whether and to what extent the bioaccessibility of the major saffron apocarotenoids, namely crocetin sugar esters (CRTSEs), is affected by the presence of strong water-soluble antioxidants, ingredients of the herbs found in commercial tea blends with saffron. [...] Read more.
The present study aims to examine whether and to what extent the bioaccessibility of the major saffron apocarotenoids, namely crocetin sugar esters (CRTSEs), is affected by the presence of strong water-soluble antioxidants, ingredients of the herbs found in commercial tea blends with saffron. An in vitro digestion model was applied to infusions from these products to investigate the possible changes. All of the studied infusions were rich in total phenols (9.9–22.5 mg caffeic acid equivalents/100 mg dry infusion) and presented strong DPPH radical scavenging activity regardless of the composition of the corresponding herbal blends. RP-HPLC-DAD and LC-MS analysis enabled the grouping of the infusions into hydroxycinnamic acid-rich and in flavan-3-ol-rich ones. CRTSEs in herbal tea infusions were found to be significantly more bioaccessible (66.3%–88.6%) than those in the reference saffron infusion (60.9%). The positive role of strong phenolic antioxidants (caffeic acid, rosmarinic acid) on the stability of CRTSEs was also evidenced in model binary mixtures. On the contrary, cinnamic acid, exerting no antioxidant activity, did not have such an effect. Our findings suggest that strong radical scavengers may protect the crocetin sugar esters from oxidation during digestion when present in excess. Full article
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Open AccessArticle In Vitro Antioxidant Activities and in Vivo Anti-Hypoxic Activity of the Edible Mushroom Agaricus bisporus (Lange) Sing. Chaidam
Molecules 2015, 20(10), 17775-17788; https://doi.org/10.3390/molecules201017775
Received: 10 June 2015 / Revised: 11 September 2015 / Accepted: 18 September 2015 / Published: 25 September 2015
Cited by 9 | Viewed by 1999 | PDF Full-text (3512 KB) | HTML Full-text | XML Full-text
Abstract
With the rising awareness of a healthy lifestyle, natural functional foods have gained much interest as promising alternatives to synthetic functional drugs. Recently, wild Agaricus bisporus (Lange) Sing. Chaidam has been found and artificially cultivated for its thick fresh body and excellent taste, [...] Read more.
With the rising awareness of a healthy lifestyle, natural functional foods have gained much interest as promising alternatives to synthetic functional drugs. Recently, wild Agaricus bisporus (Lange) Sing. Chaidam has been found and artificially cultivated for its thick fresh body and excellent taste, with its antioxidant and anti-hypoxic abilities unknown. In this work, the antioxidant potential of its methanolic, 55% ethanolic, aqueous extracts and crude polysaccharide was evaluated in different systems. The results showed that polysaccharide was the most effective in scavenging ability on 2,2-diphenyl-1-picrylhydrazyl (DPPH) and hydroxyl radicals, metal chelating activity and reducing power, with EC50 values of 0.02, 2.79, 1.29, and 1.82 mg/mL, respectively. Therefore, we further studied the anti-hypoxic activity of crude polysaccharide. The results turned out that polysaccharide (300 mg/kg) prolonged the survival time, decreased the blood urea nitrogen and lactic acid content as well as increased the liver glycogen significantly, compared with the blank control and the commercialized product Hongjingtian (p < 0.05). With such excellent activities, we purified the polysaccharide and analyzed its molecular weight (120 kDa) as well as monosaccharide components (glucose, fructose and mannose). This study indicated that wild Agaricus bisporus (Lange) Sing. Chaidam had strong potential to be exploited as an effective natural functional food to relieve oxidative and hypoxia stresses Full article
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Open AccessArticle Is Promiscuous CALB a Good Scaffold for Designing New Epoxidases?
Molecules 2015, 20(10), 17789-17806; https://doi.org/10.3390/molecules201017789
Received: 7 August 2015 / Revised: 10 September 2015 / Accepted: 11 September 2015 / Published: 25 September 2015
Cited by 3 | Viewed by 2219 | PDF Full-text (6484 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Candida Antarctica lipase B (CALB) is a well-known enzyme, especially because of its promiscuous activity. Due to its properties, CALB was widely used as a benchmark for designing new catalysts for important organic reactions. The active site of CALB is very similar to [...] Read more.
Candida Antarctica lipase B (CALB) is a well-known enzyme, especially because of its promiscuous activity. Due to its properties, CALB was widely used as a benchmark for designing new catalysts for important organic reactions. The active site of CALB is very similar to that of soluble epoxide hydrolase (sEH) formed by a nucleophile-histidine-acid catalytic triad and an oxyanion hole typical for molecular structures derived from processes of α/β hydrolases. In this work we are exploring these similarities and proposing a Ser105Asp variant of CALB as a new catalyst for epoxide hydrolysis. In particular, the hydrolysis of the trans-diphenylpropene oxide (t-DPPO) is studied by means of quantum cluster models mimicking the active site of both enzymes. Our results, based on semi-empirical and DFT calculations, suggest that mutant Ser105Asp CALB is a good protein scaffold to be used for the bio-synthesis of chiral compounds. Full article
(This article belongs to the Special Issue Phase-Transfer Catalysis)
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Open AccessArticle Glucuronoyl Esterase Screening and Characterization Assays Utilizing Commercially Available Benzyl Glucuronic Acid Ester
Molecules 2015, 20(10), 17807-17817; https://doi.org/10.3390/molecules201017807
Received: 15 July 2015 / Revised: 10 September 2015 / Accepted: 17 September 2015 / Published: 25 September 2015
Cited by 12 | Viewed by 2033 | PDF Full-text (1833 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Research on glucuronoyl esterases (GEs) has been hampered by the lack of enzyme assays based on easily obtainable substrates. While benzyl d-glucuronic acid ester (BnGlcA) is a commercially available substrate that can be used for GE assays, several considerations regarding substrate instability, limited [...] Read more.
Research on glucuronoyl esterases (GEs) has been hampered by the lack of enzyme assays based on easily obtainable substrates. While benzyl d-glucuronic acid ester (BnGlcA) is a commercially available substrate that can be used for GE assays, several considerations regarding substrate instability, limited solubility and low apparent affinities should be made. In this work we discuss the factors that are important when using BnGlcA for assaying GE activity and show how these can be applied when designing BnGlcA-based GE assays for different applications: a thin-layer chromatography assay for qualitative activity detection, a coupled-enzyme spectrophotometric assay that can be used for high-throughput screening or general activity determinations and a HPLC-based detection method allowing kinetic determinations. The three-level experimental procedure not merely facilitates routine, fast and simple biochemical characterizations but it can also give rise to the discovery of different GEs through an extensive screening of heterologous Genomic and Metagenomic expression libraries. Full article
(This article belongs to the Special Issue Biocatalytic Lignin Modification)
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Open AccessArticle Bioassay-Guided Isolation and Identification of Xanthine Oxidase Inhibitory Constituents from the Leaves of Perilla frutescens
Molecules 2015, 20(10), 17848-17859; https://doi.org/10.3390/molecules201017848
Received: 27 August 2015 / Revised: 15 September 2015 / Accepted: 22 September 2015 / Published: 25 September 2015
Cited by 25 | Viewed by 2701 | PDF Full-text (984 KB) | HTML Full-text | XML Full-text
Abstract
Activity-directed fractionation and purification processes were employed to identify xanthine oxidase (XO) inhibitory compounds from the leaves of Perilla frutescens. The total extract was evaluated in vitro on XO inhibitory activity and in vivo in an experimental model with potassium oxonate-induced hyperuricemia [...] Read more.
Activity-directed fractionation and purification processes were employed to identify xanthine oxidase (XO) inhibitory compounds from the leaves of Perilla frutescens. The total extract was evaluated in vitro on XO inhibitory activity and in vivo in an experimental model with potassium oxonate-induced hyperuricemia in mice which was used to evaluate anti-hyperuricemic activity. The crude extract showed expressive urate-lowering activity results. Solvent partitioning of the total extract followed by macroporous resin column chromatography of the n-butanol extract yielded four extracts and eluted parts. Among them, only the 70% ethanol eluted part of the n-butanol extract showed strong activity and therefore was subjected to separation and purification using various chromatographic techniques. Five compounds showing potent activity were identified by comparing their spectral data with literature values to be caffeic acid, vinyl caffeate, rosmarinic acid, methyl rosmarinate, and apigenin. These results indicate that pending further study, these compounds could be used as novel natural product agents for the treatment of hyperuricemia. Full article
(This article belongs to the collection Bioactive Compounds)
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Open AccessArticle Amination of Aryl Halides and Esters Using Intensified Continuous Flow Processing
Molecules 2015, 20(10), 17860-17871; https://doi.org/10.3390/molecules201017860
Received: 25 August 2015 / Revised: 17 September 2015 / Accepted: 22 September 2015 / Published: 25 September 2015
Cited by 1 | Viewed by 2274 | PDF Full-text (1035 KB) | HTML Full-text | XML Full-text
Abstract
Significant process intensification of the amination reactions of aryl halides and esters has been demonstrated using continuous flow processing. Using this technology traditionally difficult amination reactions have been performed safely at elevated temperatures. These reactions were successfully conducted on laboratory scale coil reactor [...] Read more.
Significant process intensification of the amination reactions of aryl halides and esters has been demonstrated using continuous flow processing. Using this technology traditionally difficult amination reactions have been performed safely at elevated temperatures. These reactions were successfully conducted on laboratory scale coil reactor modules with 1 mm internal diameter (ID) and on a preparatory scale tubular reactor with 6 mm ID containing static mixers. Full article
(This article belongs to the Special Issue Recent Advances in Flow Chemistry)
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Open AccessArticle Methanolic Extract of Ganoderma lucidum Induces Autophagy of AGS Human Gastric Tumor Cells
Molecules 2015, 20(10), 17872-17882; https://doi.org/10.3390/molecules201017872
Received: 28 July 2015 / Revised: 21 September 2015 / Accepted: 23 September 2015 / Published: 29 September 2015
Cited by 14 | Viewed by 2773 | PDF Full-text (1839 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Ganoderma lucidum is one of the most widely studied mushroom species, particularly in what concerns its medicinal properties. Previous studies (including those from some of us) have shown some evidence that the methanolic extract of G. lucidum affects cellular autophagy. However, it was [...] Read more.
Ganoderma lucidum is one of the most widely studied mushroom species, particularly in what concerns its medicinal properties. Previous studies (including those from some of us) have shown some evidence that the methanolic extract of G. lucidum affects cellular autophagy. However, it was not known if it induces autophagy or decreases the autophagic flux. The treatment of a gastric adenocarcinoma cell line (AGS) with the mushroom extract increased the formation of autophagosomes (vacuoles typical from autophagy). Moreover, the cellular levels of LC3-II were also increased, and the cellular levels of p62 decreased, confirming that the extract affects cellular autophagy. Treating the cells with the extract together with lysossomal protease inhibitors, the cellular levels of LC3-II and p62 increased. The results obtained proved that, in AGS cells, the methanolic extract of G. lucidum causes an induction of autophagy, rather than a reduction in the autophagic flux. To our knowledge, this is the first study proving that statement. Full article
(This article belongs to the collection Bioactive Compounds)
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Open AccessArticle Phytotoxic Potential and Biological Activity of Three Synthetic Coumarin Derivatives as New Natural-Like Herbicides
Molecules 2015, 20(10), 17883-17902; https://doi.org/10.3390/molecules201017883
Received: 16 July 2015 / Revised: 21 September 2015 / Accepted: 21 September 2015 / Published: 29 September 2015
Cited by 9 | Viewed by 2101 | PDF Full-text (3377 KB) | HTML Full-text | XML Full-text
Abstract
Coumarin is a natural compound well known for its phytotoxic potential. In the search for new herbicidal compounds to manage weeds, three synthetic derivatives bearing the coumarin scaffold (13), synthesized by a carbonylative organometallic approach, were in vitro assayed [...] Read more.
Coumarin is a natural compound well known for its phytotoxic potential. In the search for new herbicidal compounds to manage weeds, three synthetic derivatives bearing the coumarin scaffold (13), synthesized by a carbonylative organometallic approach, were in vitro assayed on germination and root growth of two noxious weeds, Amaranthus retroflexus and Echinochloa crus-galli. Moreover, the synthetic coumarins 13 were also in vitro assayed on seedlings growth of the model species Arabidopsis thaliana to identify the possible physiological targets. All molecules strongly affected seed germination and root growth of both weeds. Interestingly, the effects of synthetic coumarins on weed germination were higher than template natural coumarin, pointing out ED50 values ranging from 50–115 µM. Moreover, all synthetic coumarins showed a strong phytotoxic potential on both Arabidopsis shoot and root growth, causing a strong reduction in shoot fresh weight (ED50 values ≤ 60 µM), accompanied by leaf development and a decrease in pigment content. Furthermore, they caused a strong alteration in root growth (ED50 values ≤ 170 µM) and morphology with evident alterations in root tip anatomy. Taken together, our results highlight the promising potential herbicidal activity of these compounds. Full article
(This article belongs to the Special Issue Coumarins, Xanthones and Related Compounds)
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Open AccessArticle Activity of Polyphenolic Compounds against Candida glabrata
Molecules 2015, 20(10), 17903-17912; https://doi.org/10.3390/molecules201017903
Received: 15 July 2015 / Revised: 16 September 2015 / Accepted: 24 September 2015 / Published: 29 September 2015
Cited by 10 | Viewed by 1948 | PDF Full-text (696 KB) | HTML Full-text | XML Full-text
Abstract
Opportunistic mycoses increase the morbidity and mortality of immuno-compromised patients. Five Candida species have been shown to be responsible for 97% of worldwide cases of invasive candidiasis. Resistance of C. glabrata and C. krusei to azoles has been reported, and new, improved antifungal [...] Read more.
Opportunistic mycoses increase the morbidity and mortality of immuno-compromised patients. Five Candida species have been shown to be responsible for 97% of worldwide cases of invasive candidiasis. Resistance of C. glabrata and C. krusei to azoles has been reported, and new, improved antifungal agents are needed. The current study was designed to evaluatethe activity of various polyphenolic compounds against Candida species. Antifungal activity was evaluated following the M27-A3 protocol of the Clinical and Laboratory Standards Institute, and antioxidant activity was determined using the DPPH assay. Myricetin and baicalein inhibited the growth of all species tested. This effect was strongest against C. glabrata, for which the minimum inhibitory concentration (MIC) value was lower than that of fluconazole. The MIC values against C. glabrata for myricitrin, luteolin, quercetin, 3-hydroxyflavone, and fisetin were similar to that of fluconazole. The antioxidant activity of all compounds was confirmed, and polyphenolic compounds with antioxidant activity had the greatest activity against C. glabrata. The structure and position of their hydroxyl groups appear to influence their activity against C. glabrata. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Potent Activities of Roemerine against Candida albicans and the Underlying Mechanisms
Molecules 2015, 20(10), 17913-17928; https://doi.org/10.3390/molecules201017913
Received: 1 August 2015 / Revised: 7 September 2015 / Accepted: 22 September 2015 / Published: 29 September 2015
Cited by 10 | Viewed by 2142 | PDF Full-text (3735 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Roemerine (RM) is an aporphine alkaloid isolated from the fresh rattan stem of Fibraurea recisa, and it has been demonstrated to have certain antifungal activity. This study aimed to investigate the antifungal activity of RM and the underlying mechanisms in Candida albicans [...] Read more.
Roemerine (RM) is an aporphine alkaloid isolated from the fresh rattan stem of Fibraurea recisa, and it has been demonstrated to have certain antifungal activity. This study aimed to investigate the antifungal activity of RM and the underlying mechanisms in Candida albicans (C. albicans). The in vitro antifungal activity of RM was evaluated by a series of experiments, including the XTT reduction assay, confocal laser scanning microscopy assay, scanning electron microscope assay. Results showed that 1 μg/mL RM inhibited biofilm formation significantly (p < 0.01) both in Spider medium and Lee’s medium. In addition, RM could inhibit yeast-to-hyphae transition of C. albicans in a dose-dependent manner. The biofilm-specific and hypha-specific genes such as YWP1, SAP5, SAP6, HWP1, ECE1 were up-regulated and EFG1 was down-regulated after 8 μg/mL RM treatment. Furthermore, the toxicity of RM was investigated using C. elegans worms, three cancer cells and one normal cell. The date showed that RM had no significant toxicity. In conclusion, RM could inhibited the formation of C. albicans biofilm in vitro, but it had no fungicidal effect on planktonic C. albicans cells, and the anti-biofilm mechanism may be related to the cAMP pathway. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Ionic Liquid-Based Ultrasonic-Assisted Extraction of Secoisolariciresinol Diglucoside from Flaxseed (Linum usitatissimum L.) with Further Purification by an Aqueous Two-Phase System
Molecules 2015, 20(10), 17929-17943; https://doi.org/10.3390/molecules201017929
Received: 6 July 2015 / Revised: 31 August 2015 / Accepted: 10 September 2015 / Published: 30 September 2015
Cited by 12 | Viewed by 2548 | PDF Full-text (1806 KB) | HTML Full-text | XML Full-text
Abstract
In this work, a two-step extraction methodology of ionic liquid-based ultrasonic-assisted extraction (IL-UAE) and ionic liquid-based aqueous two-phase system (IL-ATPS) was developed for the extraction and purification of secoisolariciresinol diglucoside (SDG) from flaxseed. In the IL-UAE step, several kinds of ILs were investigated [...] Read more.
In this work, a two-step extraction methodology of ionic liquid-based ultrasonic-assisted extraction (IL-UAE) and ionic liquid-based aqueous two-phase system (IL-ATPS) was developed for the extraction and purification of secoisolariciresinol diglucoside (SDG) from flaxseed. In the IL-UAE step, several kinds of ILs were investigated as the extractants, to identify the IL that affords the optimum extraction yield. The extraction conditions such as IL concentration, ultrasonic irradiation time, and liquid–solid ratio were optimized using response surface methodology (RSM). In the IL-ATPS step, ATPS formed by adding kosmotropic salts to the IL extract was used for further separation and purification of SDG. The most influential parameters (type and concentration of salt, temperature, and pH) were investigated to obtain the optimum extraction efficiency. The maximum extraction efficiency was 93.35% under the optimal conditions of 45.86% (w/w) IL and 8.27% (w/w) Na2SO4 at 22 °C and pH 11.0. Thus, the combination of IL-UAE and IL-ATPS makes up a simple and effective methodology for the extraction and purification of SDG. This process is also expected to be highly useful for the extraction and purification of bioactive compounds from other important medicinal plants. Full article
(This article belongs to the Section Natural Products Chemistry)
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Open AccessArticle Comparative Studies on Phenolic Composition, Antioxidant, Wound Healing and Cytotoxic Activities of Selected Achillea L. Species Growing in Turkey
Molecules 2015, 20(10), 17976-18000; https://doi.org/10.3390/molecules201017976
Received: 28 February 2015 / Revised: 20 September 2015 / Accepted: 21 September 2015 / Published: 30 September 2015
Cited by 22 | Viewed by 3114 | PDF Full-text (2983 KB) | HTML Full-text | XML Full-text
Abstract
Turkey is one of the most important centers of diversity for the genus Achillea L. in the world. Keeping in mind the immense medicinal importance of phenols, in this study, three species growing in Turkey, A. coarctata Poir. (AC), A. kotschyi Boiss. subsp. [...] Read more.
Turkey is one of the most important centers of diversity for the genus Achillea L. in the world. Keeping in mind the immense medicinal importance of phenols, in this study, three species growing in Turkey, A. coarctata Poir. (AC), A. kotschyi Boiss. subsp. kotschyi (AK) and A. lycaonica Boiss. & Heldr. (AL) were evaluated for their phenolic compositions, total phenolic contents (TPC), antioxidant properties, wound healing potencies on NIH-3T3 fibroblasts and cytotoxic effects on MCF-7 human breast cancer cells. Comprehensive LC-MS/MS analysis revealed that AK was distinctively rich in chlorogenic acid, hyperoside, apigenin, hesperidin, rutin, kaempferol and luteolin (2890.6, 987.3, 797.0, 422.5, 188.1, 159.4 and 121.2 µg analyte/g extract, respectively). The findings exhibited a strong correlation between TPC and both free radical scavenging activity and total antioxidant capacity (TAC). Among studied species, the highest TPC (148.00 mg GAE/g extract) and TAC (2.080 UAE), the strongest radical scavenging (EC50 = 32.63 μg/mL), the most prominent wound healing and most abundant cytotoxic activities were observed with AK. The results suggested that AK is a valuable source of flavonoids and chlorogenic acid with important antioxidant, wound healing and cytotoxic activities. These findings warrant further studies to assess the potential of AK as a bioactive source that could be exploited in pharmaceutical, cosmetics and food industries. Full article
(This article belongs to the Section Natural Products Chemistry)
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Open AccessArticle Cucurbitacins from the Leaves of Citrullus colocynthis (L.) Schrad
Molecules 2015, 20(10), 18001-18015; https://doi.org/10.3390/molecules201018001
Received: 8 July 2015 / Revised: 14 September 2015 / Accepted: 23 September 2015 / Published: 30 September 2015
Cited by 11 | Viewed by 2513 | PDF Full-text (885 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Two new tetracyclic cucurbitane-type triterpene glycosides were isolated from an ethyl acetate extract of Citrullus colocynthis leaves together with four known cucurbitacins. Their structures were established on the basis of their spectroscopic data (mainly NMR and mass spectrometry). Evaluation of the in vitro [...] Read more.
Two new tetracyclic cucurbitane-type triterpene glycosides were isolated from an ethyl acetate extract of Citrullus colocynthis leaves together with four known cucurbitacins. Their structures were established on the basis of their spectroscopic data (mainly NMR and mass spectrometry). Evaluation of the in vitro cytotoxic activity of the isolated compounds against two human colon cancer cell lines (HT29 and Caco-2) and one normal rat intestine epithelial cell line (IEC6), revealed that one of the isolated compounds presented interesting specific cytotoxic activity towards colorectal cell lines. Full article
(This article belongs to the Section Natural Products Chemistry)
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Open AccessArticle Treatment Efficiency of Free and Nanoparticle-Loaded Mitoxantrone for Magnetic Drug Targeting in Multicellular Tumor Spheroids
Molecules 2015, 20(10), 18016-18030; https://doi.org/10.3390/molecules201018016
Received: 14 August 2015 / Revised: 14 September 2015 / Accepted: 24 September 2015 / Published: 30 September 2015
Cited by 12 | Viewed by 2514 | PDF Full-text (3358 KB) | HTML Full-text | XML Full-text
Abstract
Major problems of cancer treatment using systemic chemotherapy are severe side effects. Magnetic drug targeting (MDT) employing superparamagnetic iron oxide nanoparticles (SPION) loaded with chemotherapeutic agents may overcome this dilemma by increasing drug accumulation in the tumor and reducing toxic side effects in [...] Read more.
Major problems of cancer treatment using systemic chemotherapy are severe side effects. Magnetic drug targeting (MDT) employing superparamagnetic iron oxide nanoparticles (SPION) loaded with chemotherapeutic agents may overcome this dilemma by increasing drug accumulation in the tumor and reducing toxic side effects in the healthy tissue. For translation of nanomedicine from bench to bedside, nanoparticle-mediated effects have to be studied carefully. In this study, we compare the effect of SPION, unloaded or loaded with the cytotoxic drug mitoxantrone (MTO) with the effect of free MTO, on the viability and proliferation of HT-29 cells within three-dimensional multicellular tumor spheroids. Fluorescence microscopy and flow cytometry showed that both free MTO, as well as SPION-loaded MTO (SPIONMTO) are able to penetrate into tumor spheroids and thereby kill tumor cells, whereas unloaded SPION did not affect cellular viability. Since SPIONMTO has herewith proven its effectivity also in complex multicellular tumor structures with its surrounding microenvironment, we conclude that it is a promising candidate for further use in magnetic drug targeting in vivo. Full article
(This article belongs to the collection Nanomedicine)
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Open AccessArticle Plasma Pharmacokinetics of Polyphenols in a Traditional Japanese Medicine, Jumihaidokuto, Which Suppresses Propionibacterium acnes-Induced Dermatitis in Rats
Molecules 2015, 20(10), 18031-18046; https://doi.org/10.3390/molecules201018031
Received: 26 August 2015 / Revised: 24 September 2015 / Accepted: 27 September 2015 / Published: 30 September 2015
Cited by 7 | Viewed by 2881 | PDF Full-text (2480 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Most orally administered polyphenols are metabolized, with very little absorbed as aglycones and/or unchanged forms. Metabolic and pharmacokinetic studies are therefore necessary to understand the pharmacological mechanisms of polyphenols. Jumihaidokuto (JHT), a traditional Japanese medicine, has been used for treatment of skin diseases [...] Read more.
Most orally administered polyphenols are metabolized, with very little absorbed as aglycones and/or unchanged forms. Metabolic and pharmacokinetic studies are therefore necessary to understand the pharmacological mechanisms of polyphenols. Jumihaidokuto (JHT), a traditional Japanese medicine, has been used for treatment of skin diseases including inflammatory acne. Because JHT contains various types of bioactive polyphenols, our aim was to clarify the metabolism and pharmacokinetics of the polyphenols in JHT and identify active metabolites contributing to its antidermatitis effects. Orally administered JHT inhibited the increase in ear thickness in rats induced by intradermal injection of Propionibacterium acnes. Quantification by LC-MS/MS indicated that JHT contains various types of flavonoids and is also rich in hydrolysable tannins, such as 1,2,3,4,6-penta-O-galloyl glucose. Pharmacokinetic and antioxidant analyses showed that some flavonoid conjugates, such as genistein 7-O-glucuronide and liquiritigenin 7-O-glucuronide, appeared in rat plasma and had an activity to inhibit hydrogen peroxide-dependent oxidation. Furthermore, 4-O-methylgallic acid, a metabolite of Gallic acid, appeared in rat plasma and inhibited the nitric oxide reaction. JHT has numerous polyphenols; it inhibited dermatitis probably via the antioxidant effect of its metabolites. Our study is beneficial for understanding in vivo actions of orally administered polyphenol drugs. Full article
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Open AccessArticle Metabolic Profiling of Alpine and Ecuadorian Lichens
Molecules 2015, 20(10), 18047-18065; https://doi.org/10.3390/molecules201018047
Received: 14 August 2015 / Revised: 22 September 2015 / Accepted: 24 September 2015 / Published: 1 October 2015
Cited by 6 | Viewed by 2643 | PDF Full-text (2785 KB) | HTML Full-text | XML Full-text
Abstract
Non-targeted 1H-NMR methods were used to determine metabolite profiles from crude extracts of Alpine and Ecuadorian lichens collected from their natural habitats. In control experiments, the robustness of metabolite detection and quantification was estimated using replicate measurements of Stereocaulon alpinum extracts. The [...] Read more.
Non-targeted 1H-NMR methods were used to determine metabolite profiles from crude extracts of Alpine and Ecuadorian lichens collected from their natural habitats. In control experiments, the robustness of metabolite detection and quantification was estimated using replicate measurements of Stereocaulon alpinum extracts. The deviations in the overall metabolite fingerprints were low when analyzing S. alpinum collections from different locations or during different annual and seasonal periods. In contrast, metabolite profiles observed from extracts of different Alpine and Ecuadorian lichens clearly revealed genus- and species-specific profiles. The discriminating functions determining cluster formation in principle component analysis (PCA) were due to differences in the amounts of genus-specific compounds such as sticticin from the Sticta species, but also in the amounts of ubiquitous metabolites, such as sugar alcohols or trehalose. However, varying concentrations of these metabolites from the same lichen species e.g., due to different environmental conditions appeared of minor relevance for the overall cluster formation in PCA. The metabolic clusters matched phylogenetic analyses using nuclear ribosomal DNA (nrDNA) internal transcribed spacer (ITS) sequences of lichen mycobionts, as exemplified for the genus Sticta. It can be concluded that NMR-based non-targeted metabolic profiling is a useful tool in the chemo-taxonomy of lichens. The same approach could also facilitate the discovery of novel lichen metabolites on a rapid and systematical basis. Full article
(This article belongs to the Section Natural Products Chemistry)
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Open AccessArticle Antiproliferative and Apoptotic Activity of Chamaecyparis obtusa Leaf Extract against the HCT116 Human Colorectal Cancer Cell Line and Investigation of the Bioactive Compound by Gas Chromatography-Mass Spectrometry-Based Metabolomics
Molecules 2015, 20(10), 18066-18082; https://doi.org/10.3390/molecules201018066
Received: 4 September 2015 / Revised: 21 September 2015 / Accepted: 29 September 2015 / Published: 2 October 2015
Cited by 7 | Viewed by 2581 | PDF Full-text (2153 KB) | HTML Full-text | XML Full-text
Abstract
Chamaecyparis obtusa (CO) belongs to the Cupressaceae family, and it is found widely distributed in Japan and Korea. In this study, the anti-proliferative activities of the methanol and water extracts of CO leaves against a human colorectal cancer cell line (HCT116) were investigated. [...] Read more.
Chamaecyparis obtusa (CO) belongs to the Cupressaceae family, and it is found widely distributed in Japan and Korea. In this study, the anti-proliferative activities of the methanol and water extracts of CO leaves against a human colorectal cancer cell line (HCT116) were investigated. The methanol extract of CO leaves, at a concentration of 1.25 µg/mL, exhibited anti-proliferative activity against HCT116 cells, while displaying no cytotoxicity against Chang liver cells. Comparative global metabolite profiling was performed using gas chromatography-mass spectrometry coupled with multivariate statistical analysis, and it was revealed that anthricin was the major compound contributing to the anti-proliferative activity. The activation of c-Jun N-terminal kinases played a key role in the apoptotic effect of the methanol extract of CO leaves in HCT116 human colon cancer cells. These results suggest that the methanol extract and anthricin derived from CO leaves might be useful in the development of medicines with anti-colorectal cancer activity. Full article
(This article belongs to the Special Issue Applications of Metabolomics within Natural Products Chemistry)
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Open AccessArticle Quantification of Coumarins in Aqueous Extract of Pterocaulon balansae (Asteraceae) and Characterization of a New Compound
Molecules 2015, 20(10), 18083-18094; https://doi.org/10.3390/molecules201018083
Received: 13 August 2015 / Revised: 16 September 2015 / Accepted: 17 September 2015 / Published: 2 October 2015
Cited by 7 | Viewed by 2190 | PDF Full-text (758 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Plants from the genus Pterocaulon are popularly used as antifungal and wound-healing agents. Such activities have been related to coumarins, which are abundant in those plants. Coumarins are soluble in organic solvents, such as hexane and dichloromethane, and some of them are also [...] Read more.
Plants from the genus Pterocaulon are popularly used as antifungal and wound-healing agents. Such activities have been related to coumarins, which are abundant in those plants. Coumarins are soluble in organic solvents, such as hexane and dichloromethane, and some of them are also soluble in hot water. Considering that infusion and decoctions of these plants are used in traditional medicine, the aim of this study was to identify and quantify the coumarins in the aqueous extract of Pterocaulon balansae. The aqueous extract was obtained by dynamic maceration and the compounds were characterized by UPLC-UV-MS analysis. A new coumarin and 5-methoxy-6,7-methylenedioxycoumarin, used for validation of the analytical HPLC method were obtained by partition of the aqueous extract with n-hexane. The HPLC method validated was linear, specific, and precise. Seven coumarins were characterized in the aqueous extract in a range of 0.584–54 mg/g of dry plant material. The main compound, 5,6-dimethoxy-7-(3′-methyl-2′,3′-dihydroxybutyloxy)coumarin, is described for the first time in P. balansae together with a new compound, 5,6-dimethoxy-7-(2′,3′-epoxy-3′-methylbutyloxy)coumarin. Full article
(This article belongs to the Special Issue Coumarins, Xanthones and Related Compounds)
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Open AccessArticle Characterization of Non-Anthocyanic Flavonoids in Some Hybrid Red Grape Extracts Potentially Interesting for Industrial Uses
Molecules 2015, 20(10), 18095-18106; https://doi.org/10.3390/molecules201018095
Received: 7 August 2015 / Revised: 24 September 2015 / Accepted: 30 September 2015 / Published: 2 October 2015
Cited by 9 | Viewed by 1978 | PDF Full-text (717 KB) | HTML Full-text | XML Full-text
Abstract
Previous studies showed that hybrid grapes often have qualitatively and quantitatively higher polyphenolic contents than the common V. vinifera grape varieties. In general, these compounds are studied for grape chemotaxonomy and for nutraceutical purposes due to their relevant antioxidant activity. Non-anthocyanic flavonoid composition [...] Read more.
Previous studies showed that hybrid grapes often have qualitatively and quantitatively higher polyphenolic contents than the common V. vinifera grape varieties. In general, these compounds are studied for grape chemotaxonomy and for nutraceutical purposes due to their relevant antioxidant activity. Non-anthocyanic flavonoid composition of five red hybrid grape varieties produced by crossing of V. vinifera, V. aestivalis, V. cinerea, V. berlandieri, V. labrusca, V. lincecumii, and V. rupestris were studied by liquid chromatography/high-resolution mass spectrometry. Thirty-one compounds were identified, including methylnaringenin, a tetrahydroxy-dimethoxyflavanone-hexoside, two flavonols (quercetin and a pentahydroxyflavone isomer), 20 glycoside flavonols (four quercetin, two myricetin, two kaempferol, three isorhamnetin, one laricitrin, two syringetin, one kaempferide and two dihydroflavonol derivatives; myricetin-glucoside-glucuronide; myricetin-diglucoside; syringetin-dihexoside), three flavan-3-ols (−)-epicatechin, (+)-catechin, (−)-epicatechin gallate) and four proantocyanidins (procyanidin B1, procyanidin B2, procyanidin B3 or B4/B5, procyanidin T2 or T3/T4/C1). Seibel 19881, Seyve Villard 12-347 and Seyve Villard 29-399 were particularly rich in polyphenols. These findings emphasize that these grapes are especially interesting for the production of antioxidant extracts for nutraceutical and pharmaceutical uses. Full article
(This article belongs to the Section Natural Products Chemistry)
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Open AccessArticle A Quantum-Based Similarity Method in Virtual Screening
Molecules 2015, 20(10), 18107-18127; https://doi.org/10.3390/molecules201018107
Received: 26 August 2015 / Revised: 22 September 2015 / Accepted: 23 September 2015 / Published: 2 October 2015
Cited by 8 | Viewed by 2291 | PDF Full-text (741 KB) | HTML Full-text | XML Full-text
Abstract
One of the most widely-used techniques for ligand-based virtual screening is similarity searching. This study adopted the concepts of quantum mechanics to present as state-of-the-art similarity method of molecules inspired from quantum theory. The representation of molecular compounds in mathematical quantum space plays [...] Read more.
One of the most widely-used techniques for ligand-based virtual screening is similarity searching. This study adopted the concepts of quantum mechanics to present as state-of-the-art similarity method of molecules inspired from quantum theory. The representation of molecular compounds in mathematical quantum space plays a vital role in the development of quantum-based similarity approach. One of the key concepts of quantum theory is the use of complex numbers. Hence, this study proposed three various techniques to embed and to re-represent the molecular compounds to correspond with complex numbers format. The quantum-based similarity method that developed in this study depending on complex pure Hilbert space of molecules called Standard Quantum-Based (SQB). The recall of retrieved active molecules were at top 1% and top 5%, and significant test is used to evaluate our proposed methods. The MDL drug data report (MDDR), maximum unbiased validation (MUV) and Directory of Useful Decoys (DUD) data sets were used for experiments and were represented by 2D fingerprints. Simulated virtual screening experiment show that the effectiveness of SQB method was significantly increased due to the role of representational power of molecular compounds in complex numbers forms compared to Tanimoto benchmark similarity measure. Full article
(This article belongs to the Special Issue Chemoinformatics)
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Open AccessArticle Phytochemical and Biological Investigation of Two Diplotaxis Species Growing in Tunisia: D. virgata & D. erucoides
Molecules 2015, 20(10), 18128-18143; https://doi.org/10.3390/molecules201018128
Received: 24 July 2015 / Revised: 11 August 2015 / Accepted: 13 August 2015 / Published: 5 October 2015
Cited by 6 | Viewed by 1896 | PDF Full-text (764 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A phytochemical investigation of Diplotaxis virgata D.C. and D. erucoides (L.) D.C. (Brassicaceae) offered to the isolation of two new flavonoids isorhamnetin-3-O-α-l-glucopyranoside (1) and rhamnetin-3,3ʹ-di-O-β-d-glucopyranoside (2), respectively. Their structures have been elucidated from [...] Read more.
A phytochemical investigation of Diplotaxis virgata D.C. and D. erucoides (L.) D.C. (Brassicaceae) offered to the isolation of two new flavonoids isorhamnetin-3-O-α-l-glucopyranoside (1) and rhamnetin-3,3ʹ-di-O-β-d-glucopyranoside (2), respectively. Their structures have been elucidated from the extended spectroscopic methods, including 1D- and 2D-NMR, UV and mass spectrometry analysis and by comparison with literature data. The fatty acid composition of the hexane extracts of the two species was also investigated by using GC-MS. The antioxidant activity of ethanol, ethyl acetate, n-butanol extracts and the isolated compounds from the two species was evaluated using DPPH and ABTS+ scavenging assays. All the tested samples showed an efficient radical scavenging ability, with IC50 values ranging from 16–40 µg/mL for the DPPH and from 17–44 µg/mL for the ABTS+ assays. In addition, the antibacterial activity of the prepared extracts and compounds 1 and 2, determined by well diffusion agar method against two Gram positive and five Gram negative bacteria, was evaluated and the results showed significant effects against all strains used. Full article
(This article belongs to the Section Natural Products Chemistry)
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Open AccessArticle Antibacterial Activity, Antioxidant Effect and Chemical Composition of Propolis from the Región del Maule, Central Chile
Molecules 2015, 20(10), 18144-18167; https://doi.org/10.3390/molecules201018144
Received: 16 July 2015 / Revised: 28 September 2015 / Accepted: 29 September 2015 / Published: 6 October 2015
Cited by 24 | Viewed by 2853 | PDF Full-text (1920 KB) | HTML Full-text | XML Full-text
Abstract
Propolis is commercialized in Chile as an antimicrobial agent. It is obtained mainly from central and southern Chile, but is used for the same purposes regardless of its origin. To compare the antimicrobial effect, the total phenolic (TP), the total flavonoid (TF) content [...] Read more.
Propolis is commercialized in Chile as an antimicrobial agent. It is obtained mainly from central and southern Chile, but is used for the same purposes regardless of its origin. To compare the antimicrobial effect, the total phenolic (TP), the total flavonoid (TF) content and the phenolic composition, 19 samples were collected in the main production centers in the Región del Maule, Chile. Samples were extracted with MeOH and assessed for antimicrobial activity against Gram (+) and Gram (−) bacteria. TP and TF content, antioxidant activity by the DPPH, FRAP and TEAC methods were also determined. Sample composition was assessed by HPLD-DAD-ESI-MS/MS. Differential compounds in the samples were isolated and characterized. The antimicrobial effect of the samples showed MICs ranging from 31.5 to > 1000 µg/mL. Propolis from the central valley was more effective as antibacterial than those from the coastal area or Andean slopes. The samples considered of interest (MIC ≤ 62.5 µg/mL) showed effect on Escherichia coli, Pseudomonas sp., Yersinia enterocolitica and Salmonella enteritidis. Two new diarylheptanoids, a diterpene, the flavonoids pinocembrin and chrysin were isolated and elucidated by spectroscopic and spectrometric means. Some 29 compounds were dereplicated by HPLC-MS and tentatively identified, including nine flavones/flavonol derivatives, one flavanone, eight dihydroflavonols and nine phenyl-propanoids. Propolis from the Región del Maule showed large variation in antimicrobial effect, antioxidant activity and composition. So far the presence of diarylheptanoids in samples from the coastal area of central Chile can be considered as a marker of a new type of propolis. Full article
(This article belongs to the Special Issue Recent Advances in Plant Phenolics)
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Open AccessArticle Synthesis and Preliminary Evaluation of N-Oxide Derivatives for the Prevention of Atherothrombotic Events
Molecules 2015, 20(10), 18185-18200; https://doi.org/10.3390/molecules201018185
Received: 17 August 2015 / Revised: 5 September 2015 / Accepted: 15 September 2015 / Published: 7 October 2015
Cited by 8 | Viewed by 2026 | PDF Full-text (1073 KB) | HTML Full-text | XML Full-text
Abstract
Thrombosis is the main outcome of many cardiovascular diseases. Current treatments to prevent thrombotic events involve the long-term use of antiplatelet drugs. However, this therapy has several limitations, thereby justifying the development of new drugs. A series of N-oxide derivatives (furoxan and [...] Read more.
Thrombosis is the main outcome of many cardiovascular diseases. Current treatments to prevent thrombotic events involve the long-term use of antiplatelet drugs. However, this therapy has several limitations, thereby justifying the development of new drugs. A series of N-oxide derivatives (furoxan and benzofuroxan) were synthesized and characterized as potential antiplatelet/antithrombotic compounds. All compounds (3a,b, 4a,b, 8a,b, 9a,b, 13a,b and 14a,b) inhibited platelet aggregation induced by adenosine-5-diphosphate, collagen, and arachidonic acid. All compounds protected mice from pulmonary thromboembolism induced by a mixture of collagen and epinephrine; however, benzofuroxan derivatives (13a,b and 14a,b) were the most active compounds, reducing thromboembolic events by up to 80%. N-oxide derivative 14a did not induce genotoxicity in vivo. In conclusion, 14a has emerged as a new antiplatelet/antithrombotic prototype useful for the prevention of atherothrombotic events. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Synthesis of Some Novel Heterocyclic and Schiff Base Derivatives as Antimicrobial Agents
Molecules 2015, 20(10), 18201-18218; https://doi.org/10.3390/molecules201018201
Received: 5 September 2015 / Revised: 20 September 2015 / Accepted: 23 September 2015 / Published: 7 October 2015
Cited by 14 | Viewed by 3172 | PDF Full-text (864 KB) | HTML Full-text | XML Full-text
Abstract
Treatment of 2,3-diaryloxirane-2,3-dicarbonitriles 1ac with different nitrogen nucleophiles, e.g., hydrazine, methyl hydrazine, phenyl hydrazine, hydroxylamine, thiosemicarbazide, and/or 2-amino-5-phenyl-1,3,4-thiadiazole, afforded pyrazole, isoxazole, pyrrolotriazine, imidazolothiadiazole derivatives 25, respectively. Reacting pyrazoles 2ac with aromatic aldehydes and/or methyl glycinate produced [...] Read more.
Treatment of 2,3-diaryloxirane-2,3-dicarbonitriles 1ac with different nitrogen nucleophiles, e.g., hydrazine, methyl hydrazine, phenyl hydrazine, hydroxylamine, thiosemicarbazide, and/or 2-amino-5-phenyl-1,3,4-thiadiazole, afforded pyrazole, isoxazole, pyrrolotriazine, imidazolothiadiazole derivatives 25, respectively. Reacting pyrazoles 2ac with aromatic aldehydes and/or methyl glycinate produced Schiff’s bases 7ad and pyrazolo[3,4-b]-pyrazinone derivative 8, respectively. Treating 7 with ammonium acetate and/or hydrazine hydrate, furnished the imidazolopyrazole and pyrazolotriazine derivatives 9 and 10, respectively. Reaction of 8 with chloroacetic acid and/or diethyl malonate gave tricyclic compound 11 and triketone 12, respectively. On the other hand, compound 1 was reacted with active methylene precursors, e.g., acetylacetone and/or cyclopentanone producing adducts 14a,b which upon fusion with ammonium acetate furnished the 3-pyridone derivatives 15a,b, respectively. Some of newly synthesized compounds were screened for activity against bacterial and fungal strains and most of the newly synthesized compounds showed high antimicrobial activities. The structures of the new compounds were elucidated using IR, 1H-NMR, 13C-NMR and mass spectroscopy. Full article
(This article belongs to the collection Heterocyclic Compounds)
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Open AccessArticle Potential of Essential Oils as Penetration Enhancers for Transdermal Administration of Ibuprofen to Treat Dysmenorrhoea
Molecules 2015, 20(10), 18219-18236; https://doi.org/10.3390/molecules201018219
Received: 3 September 2015 / Revised: 27 September 2015 / Accepted: 28 September 2015 / Published: 7 October 2015
Cited by 21 | Viewed by 3020 | PDF Full-text (895 KB) | HTML Full-text | XML Full-text
Abstract
The present study was conducted to evaluate and compare five essential oils (EOs) as penetration enhancers (PEs) to improve the transdermal drug delivery (TDD) of ibuprofen to treat dysmenorrhoea. The EOs were prepared using the steam distillation method and their chemical compositions were [...] Read more.
The present study was conducted to evaluate and compare five essential oils (EOs) as penetration enhancers (PEs) to improve the transdermal drug delivery (TDD) of ibuprofen to treat dysmenorrhoea. The EOs were prepared using the steam distillation method and their chemical compositions were identified by GC-MS. The corresponding cytotoxicities were evaluated in epidermal keartinocyte HaCaT cell lines by an MTT assay. Furthermore, the percutaneous permeation studies were carried out to compare the permeation enhancement effect of EOs. Then the therapeutic efficacy of ibuprofen with EOs was evaluated using dysmenorrheal model mice. The data supports a decreasing trend of skin cell viability in which Clove oil >Angelica oil > Chuanxiong oil > Cyperus oil > Cinnamon oil >> Azone. Chuanxiong oil and Angelica oil had been proved to possess a significant permeation enhancement for TDD of ibuprofen. More importantly, the pain inhibitory intensity of ibuprofen hydrogel was demonstrated to be greater with Chuanxiong oil when compared to ibuprofen without EOs (p < 0.05). The contents of calcium ion and nitric oxide (NO) were also significantly changed after the addition of Chuanxiong oil (p < 0.05). In summary, we suggest that Chuanxiong oil should be viewed as the best PE for TDD of ibuprofen to treat dysmenorrhea. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Ring Opening Reactions through C-O Bond Cleavage Uniquely Adding Chemical Functionality to Boron Subphthalocyanine
Molecules 2015, 20(10), 18237-18245; https://doi.org/10.3390/molecules201018237
Received: 30 July 2015 / Revised: 16 September 2015 / Accepted: 21 September 2015 / Published: 7 October 2015
Cited by 2 | Viewed by 2070 | PDF Full-text (759 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
We are reporting the unexpected reaction between bromo-boron subphthalocyanine (Br-BsubPc) and THF, 1,4-dioxane or γ-butyrolactone that results in the ring opening of the solvent and its addition into the BsubPc moiety. Under heating, the endocyclic C-O bond of the solvent is cleaved and [...] Read more.
We are reporting the unexpected reaction between bromo-boron subphthalocyanine (Br-BsubPc) and THF, 1,4-dioxane or γ-butyrolactone that results in the ring opening of the solvent and its addition into the BsubPc moiety. Under heating, the endocyclic C-O bond of the solvent is cleaved and the corresponding bromoalkoxy-BsubPc derivative is obtained. These novel alkoxy-BsubPc derivatives have remaining alkyl-bromides suitable for further functionalization. The alkoxy-BsubPcs maintain the characteristic strongly absorption in visible spectrum and their fluorescence quantum yields. Full article
(This article belongs to the Special Issue Tetrapyrroles, Porphyrins and Phthalocyanines)
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Open AccessArticle Lead Optimization of 2-Cyclohexyl-N-[(Z)-(3-methoxyphenyl/3-hydroxyphenyl) methylidene]hydrazinecarbothioamides for Targeting the HER-2 Overexpressed Breast Cancer Cell Line SKBr-3
Molecules 2015, 20(10), 18246-18263; https://doi.org/10.3390/molecules201018246
Received: 19 June 2015 / Revised: 2 October 2015 / Accepted: 2 October 2015 / Published: 7 October 2015
Cited by 5 | Viewed by 1935 | PDF Full-text (1477 KB) | HTML Full-text | XML Full-text
Abstract
Lead derivatives of 2-cyclohexyl-N-[(Z)-(3-methoxyphenyl/3-hydroxyphenyl) methylidene]hydrazinecarbothioamides 118 were synthesized, characterized and evaluated in vitro against HER-2 overexpressed breast cancer cell line SKBr-3. All the compounds showed activity against HER-2 overexpressed SKBr-3 cells with IC50 = 17.44 ± [...] Read more.
Lead derivatives of 2-cyclohexyl-N-[(Z)-(3-methoxyphenyl/3-hydroxyphenyl) methylidene]hydrazinecarbothioamides 118 were synthesized, characterized and evaluated in vitro against HER-2 overexpressed breast cancer cell line SKBr-3. All the compounds showed activity against HER-2 overexpressed SKBr-3 cells with IC50 = 17.44 ± 0.01 µM to 53.29 ± 0.33 µM. (2Z)-2-(3-Hydroxybenzylidene)-N-(3-methoxyphenyl)hydrazinecarbothioamide (12, IC50 = 17.44 ± 0.01 µM) was found to be most potent compound of this series targeting HER-2 overexpressed breast cancer cells compared to the standard drug 5-fluorouracil (5-FU) (IC50 = 38.58 ± 0.04 µM). Compound 12 inhibited the cellular proliferation via DNA degradation. Full article
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Open AccessArticle New Non-Toxic Semi-Synthetic Derivatives from Natural Diterpenes Displaying Anti-Tuberculosis Activity
Molecules 2015, 20(10), 18264-18278; https://doi.org/10.3390/molecules201018264
Received: 25 August 2015 / Revised: 30 September 2015 / Accepted: 30 September 2015 / Published: 7 October 2015
Cited by 5 | Viewed by 2102 | PDF Full-text (742 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
We report herein the synthesis of six diterpene derivatives, three of which are new, generated through known organic chemistry reactions that allowed structural modification of the existing natural products kaurenoic acid (1) and copalic acid (2). The new compounds [...] Read more.
We report herein the synthesis of six diterpene derivatives, three of which are new, generated through known organic chemistry reactions that allowed structural modification of the existing natural products kaurenoic acid (1) and copalic acid (2). The new compounds were fully characterized using high resolution mass spectrometry, infrared spectroscopy, 1H- and 13C-NMR experiments. We also report the evaluation of the anti-tuberculosis potential for all compounds, which showed some promising results for Micobacterium tuberculosis inhibition. Moreover, the toxicity for each of the most active compounds was also assessed. Full article
(This article belongs to the Section Natural Products Chemistry)
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Open AccessArticle A Generally Applicable Computer Algorithm Based on the Group Additivity Method for the Calculation of Seven Molecular Descriptors: Heat of Combustion, LogPO/W, LogS, Refractivity, Polarizability, Toxicity and LogBB of Organic Compounds; Scope and Limits of Applicability
Molecules 2015, 20(10), 18279-18351; https://doi.org/10.3390/molecules201018279
Received: 5 August 2015 / Revised: 25 September 2015 / Accepted: 29 September 2015 / Published: 7 October 2015
Cited by 8 | Viewed by 2014 | PDF Full-text (5766 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A generally applicable computer algorithm for the calculation of the seven molecular descriptors heat of combustion, logPoctanol/water, logS (water solubility), molar refractivity, molecular polarizability, aqueous toxicity (protozoan growth inhibition) and logBB (log (cblood/cbrain)) is presented. The method, [...] Read more.
A generally applicable computer algorithm for the calculation of the seven molecular descriptors heat of combustion, logPoctanol/water, logS (water solubility), molar refractivity, molecular polarizability, aqueous toxicity (protozoan growth inhibition) and logBB (log (cblood/cbrain)) is presented. The method, an extendable form of the group-additivity method, is based on the complete break-down of the molecules into their constituting atoms and their immediate neighbourhood. The contribution of the resulting atom groups to the descriptor values is calculated using the Gauss-Seidel fitting method, based on experimental data gathered from literature. The plausibility of the method was tested for each descriptor by means of a k-fold cross-validation procedure demonstrating good to excellent predictive power for the former six descriptors and low reliability of logBB predictions. The goodness of fit (Q2) and the standard deviation of the 10-fold cross-validation calculation was >0.9999 and 25.2 kJ/mol, respectively, (based on N = 1965 test compounds) for the heat of combustion, 0.9451 and 0.51 (N = 2640) for logP, 0.8838 and 0.74 (N = 1419) for logS, 0.9987 and 0.74 (N = 4045) for the molar refractivity, 0.9897 and 0.77 (N = 308) for the molecular polarizability, 0.8404 and 0.42 (N = 810) for the toxicity and 0.4709 and 0.53 (N = 383) for logBB. The latter descriptor revealing a very low Q2 for the test molecules (R2 was 0.7068 and standard deviation 0.38 for N = 413 training molecules) is included as an example to show the limits of the group-additivity method. An eighth molecular descriptor, the heat of formation, was indirectly calculated from the heat of combustion data and correlated with published experimental heat of formation data with a correlation coefficient R2 of 0.9974 (N = 2031). Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Characterization and Quantification by LC-MS/MS of the Chemical Components of the Heating Products of the Flavonoids Extract in Pollen Typhae for Transformation Rule Exploration
Molecules 2015, 20(10), 18352-18366; https://doi.org/10.3390/molecules201018352
Received: 5 August 2015 / Revised: 28 September 2015 / Accepted: 1 October 2015 / Published: 8 October 2015
Cited by 21 | Viewed by 2231 | PDF Full-text (853 KB) | HTML Full-text | XML Full-text
Abstract
The Traditional Chinese Medicine herbs Pollen Typhae and Pollen Typhae Carbonisatus have been used as a hemostatic medicine promoting blood clotting for thousands of years. In this study, a reliable, highly sensitive method based on LC-MS/MS has been developed for differentiation of the [...] Read more.
The Traditional Chinese Medicine herbs Pollen Typhae and Pollen Typhae Carbonisatus have been used as a hemostatic medicine promoting blood clotting for thousands of years. In this study, a reliable, highly sensitive method based on LC-MS/MS has been developed for differentiation of the heating products of total flavonoids in Pollen Typhae (FPT-N). Twenty three peaks were detected and 18 peaks have been structurally identified by comparing retention times, high resolution mass spectrometry data, and fragment ions with those of the reference substances and/or literature data. Additionally, 15 compounds have been quantified by multiple reaction monitoring in the negative ionization mode. It was found that the contents of the characterized compounds differed greatly from each other in FPT-N samples. Among them, the content of huaicarbon B significantly increased at first, while it decreased after heating for 25 min, which could be considered as the characteristic component for distinguishing FPT-N. The present study provided an approach to rapidly distinguish the differences of FPT-N samples. In addition, the actively summarized characteristic fragmentation might help deducing the structure of unknown flavonols compounds. Furthermore, transformation rules of flavonoids during the heating process in carbonisatus development could contribute to hemostatic therapeutic component exploration. Full article
(This article belongs to the Section Natural Products Chemistry)
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Open AccessArticle Synthesis and Spectroscopic Evaluation of Two Novel Glycosylated Zinc(II)-Phthalocyanines
Molecules 2015, 20(10), 18367-18386; https://doi.org/10.3390/molecules201018367
Received: 23 September 2015 / Revised: 5 October 2015 / Accepted: 6 October 2015 / Published: 9 October 2015
Cited by 5 | Viewed by 2284 | PDF Full-text (1718 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In continuation of our work on glycoconjugated phthalocyanines, two new water soluble, non-ionic zinc(II) phthalocyanines have been prepared and fully characterized by means of 1H-NMR, 13C-NMR, MALDI-TOF, ESI-TOF, UV-Vis spectroscopy, emission spectroscopy and fluorescence lifetime measurements. The carbohydrate-containing phthalonitrile precursors were [...] Read more.
In continuation of our work on glycoconjugated phthalocyanines, two new water soluble, non-ionic zinc(II) phthalocyanines have been prepared and fully characterized by means of 1H-NMR, 13C-NMR, MALDI-TOF, ESI-TOF, UV-Vis spectroscopy, emission spectroscopy and fluorescence lifetime measurements. The carbohydrate-containing phthalonitrile precursors were synthesized through a copper-catalyzed azide-alkyne cycloaddition (CuAAC). The 2-methoxyethoxymethyl protecting group (MEM) was used to protect the carbohydrate moieties. It resisted the harsh basic cyclotetramerization conditions and could be easily cleaved under mild acidic conditions. The glycoconjugated zinc(II) phthalocyanines described here have molar extinction coefficents εmax > 105 m−1 cm−1 and absorption maxima λ > 680 nm, which make them attractive photosensitizers for photo-dynamic therapy. Full article
(This article belongs to the Special Issue Tetrapyrroles, Porphyrins and Phthalocyanines)
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Open AccessArticle A Promising PET Tracer for Imaging of α7 Nicotinic Acetylcholine Receptors in the Brain: Design, Synthesis, and in Vivo Evaluation of a Dibenzothiophene-Based Radioligand
Molecules 2015, 20(10), 18387-18421; https://doi.org/10.3390/molecules201018387
Received: 15 July 2015 / Revised: 25 September 2015 / Accepted: 28 September 2015 / Published: 9 October 2015
Cited by 6 | Viewed by 2896 | PDF Full-text (1677 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Changes in the expression of α7 nicotinic acetylcholine receptors (α7 nAChRs) in the human brain are widely assumed to be associated with neurological and neurooncological processes. Investigation of these receptors in vivo depends on the availability of imaging agents such as [...] Read more.
Changes in the expression of α7 nicotinic acetylcholine receptors (α7 nAChRs) in the human brain are widely assumed to be associated with neurological and neurooncological processes. Investigation of these receptors in vivo depends on the availability of imaging agents such as radioactively labelled ligands applicable in positron emission tomography (PET). We report on a series of new ligands for α7 nAChRs designed by the combination of dibenzothiophene dioxide as a novel hydrogen bond acceptor functionality with diazabicyclononane as an established cationic center. To assess the structure-activity relationship (SAR) of this new basic structure, we further modified the cationic center systematically by introduction of three different piperazine-based scaffolds. Based on in vitro binding affinity and selectivity, assessed by radioligand displacement studies at different rat and human nAChR subtypes and at the structurally related human 5-HT3 receptor, we selected the compound 7-(1,4-diazabicyclo[3.2.2]nonan-4-yl)-2-fluorodibenzo-[b,d]thiophene 5,5-dioxide (10a) for radiolabeling and further evaluation in vivo. Radiosynthesis of [18F]10a was optimized and transferred to an automated module. Dynamic PET imaging studies with [18F]10a in piglets and a monkey demonstrated high uptake of radioactivity in the brain, followed by washout and target-region specific accumulation under baseline conditions. Kinetic analysis of [18F]10a in pig was performed using a two-tissue compartment model with arterial-derived input function. Our initial evaluation revealed that the dibenzothiophene-based PET radioligand [18F]10a ([18F]DBT-10) has high potential to provide clinically relevant information about the expression and availability of α7 nAChR in the brain. Full article
(This article belongs to the Special Issue Preparation of Radiopharmaceuticals and Their Use in Drug Development)
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Open AccessArticle Contribution of Bacillus Isolates to the Flavor Profiles of Vanilla Beans Assessed through Aroma Analysis and Chemometrics
Molecules 2015, 20(10), 18422-18436; https://doi.org/10.3390/molecules201018422
Received: 5 August 2015 / Revised: 11 September 2015 / Accepted: 17 September 2015 / Published: 9 October 2015
Cited by 2 | Viewed by 2121 | PDF Full-text (1538 KB) | HTML Full-text | XML Full-text
Abstract
Colonizing Bacillus in vanilla (Vanilla planifolia Andrews) beans is involved in glucovanillin hydrolysis and vanillin formation during conventional curing. The flavor profiles of vanilla beans under Bacillus-assisted curing were analyzed through gas chromatography-mass spectrometry, electronic nose, and quantitative sensory analysis. The [...] Read more.
Colonizing Bacillus in vanilla (Vanilla planifolia Andrews) beans is involved in glucovanillin hydrolysis and vanillin formation during conventional curing. The flavor profiles of vanilla beans under Bacillus-assisted curing were analyzed through gas chromatography-mass spectrometry, electronic nose, and quantitative sensory analysis. The flavor profiles were analytically compared among the vanilla beans under Bacillus-assisted curing, conventional curing, and non-microorganism-assisted curing. Vanilla beans added with Bacillus vanillea XY18 and Bacillus subtilis XY20 contained higher vanillin (3.58% ± 0.05% and 3.48% ± 0.10%, respectively) than vanilla beans that underwent non-microorganism-assisted curing and conventional curing (3.09% ± 0.14% and 3.21% ± 0.15%, respectively). Forty-two volatiles were identified from endogenous vanilla metabolism. Five other compounds were identified from exogenous Bacillus metabolism. Electronic nose data confirmed that vanilla flavors produced through the different curing processes were easily distinguished. Quantitative sensory analysis confirmed that Bacillus-assisted curing increased vanillin production without generating any unpleasant sensory attribute. Partial least squares regression further provided a correlation model of different measurements. Overall, we comparatively analyzed the flavor profiles of vanilla beans under Bacillus-assisted curing, indirectly demonstrated the mechanism of vanilla flavor formation by microbes. Full article
(This article belongs to the collection Recent Advances in Flavors and Fragrances)
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Open AccessArticle Cladribine Analogues via O6-(Benzotriazolyl) Derivatives of Guanine Nucleosides
Molecules 2015, 20(10), 18437-18463; https://doi.org/10.3390/molecules201018437
Received: 17 August 2015 / Revised: 20 September 2015 / Accepted: 22 September 2015 / Published: 9 October 2015
Cited by 6 | Viewed by 2986 | PDF Full-text (1310 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Cladribine, 2-chloro-2′-deoxyadenosine, is a highly efficacious, clinically used nucleoside for the treatment of hairy cell leukemia. It is also being evaluated against other lymphoid malignancies and has been a molecule of interest for well over half a century. In continuation of our interest [...] Read more.
Cladribine, 2-chloro-2′-deoxyadenosine, is a highly efficacious, clinically used nucleoside for the treatment of hairy cell leukemia. It is also being evaluated against other lymphoid malignancies and has been a molecule of interest for well over half a century. In continuation of our interest in the amide bond-activation in purine nucleosides via the use of (benzotriazol-1yl-oxy)tris(dimethylamino)phosphonium hexafluorophosphate, we have evaluated the use of O6-(benzotriazol-1-yl)-2′-deoxyguanosine as a potential precursor to cladribine and its analogues. These compounds, after appropriate deprotection, were assessed for their biological activities, and the data are presented herein. Against hairy cell leukemia (HCL), T-cell lymphoma (TCL) and chronic lymphocytic leukemia (CLL), cladribine was the most active against all. The bromo analogue of cladribine showed comparable activity to the ribose analogue of cladribine against HCL, but was more active against TCL and CLL. The bromo ribose analogue of cladribine showed activity, but was the least active among the C6-NH2-containing compounds. Substitution with alkyl groups at the exocyclic amino group appears detrimental to activity, and only the C6 piperidinyl cladribine analogue demonstrated any activity. Against adenocarcinoma MDA-MB-231 cells, cladribine and its ribose analogue were most active. Full article
(This article belongs to the Special Issue Nucleoside Modifications) Printed Edition available
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Open AccessArticle A Mild and Regioselective Ring-Opening of Aziridines with Acid Anhydride Using TBD or PS-TBD as a Catalyst
Molecules 2015, 20(10), 18482-18495; https://doi.org/10.3390/molecules201018482
Received: 2 September 2015 / Revised: 22 September 2015 / Accepted: 23 September 2015 / Published: 9 October 2015
Cited by 5 | Viewed by 2087 | PDF Full-text (756 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The ring-opening of N-tosylaziridines with various acid anhydrides catalyzed by 5 mol % of 1,5,7-triazabicyclo[4,4,0]dec-5-ene (TBD) afforded the corresponding β-amino esters in excellent yields under mild reaction conditions. Polymer-supported catalyst, PS-TBD also acts as a good catalyst for this reaction. PS-TBD was [...] Read more.
The ring-opening of N-tosylaziridines with various acid anhydrides catalyzed by 5 mol % of 1,5,7-triazabicyclo[4,4,0]dec-5-ene (TBD) afforded the corresponding β-amino esters in excellent yields under mild reaction conditions. Polymer-supported catalyst, PS-TBD also acts as a good catalyst for this reaction. PS-TBD was easily recovered and reused with minimal loss of activity. Full article
(This article belongs to the Special Issue Brønsted Base Catalysis in Organic Synthesis)
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Open AccessArticle Anti-Inflammatory Constituents from Bidens frondosa
Molecules 2015, 20(10), 18496-18510; https://doi.org/10.3390/molecules201018496
Received: 31 August 2015 / Revised: 25 September 2015 / Accepted: 29 September 2015 / Published: 9 October 2015
Cited by 9 | Viewed by 2072 | PDF Full-text (974 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A new polyacetylene glucoside (3E,5E,11E)-tridecatriene-7,9-diyne-1,2,13-triol-2-O-β-d-glucopyranoside (1), a new phenylpropanoid glucoside 2′-butoxyethylconiferin (2), and a new flavonoid glycoside 8,3′,4′-trihydroxyflavone-7-O-(6′′-O-p-coumaroyl)-β-d-glucopyranoside (3), have been isolated from [...] Read more.
A new polyacetylene glucoside (3E,5E,11E)-tridecatriene-7,9-diyne-1,2,13-triol-2-O-β-d-glucopyranoside (1), a new phenylpropanoid glucoside 2′-butoxyethylconiferin (2), and a new flavonoid glycoside 8,3′,4′-trihydroxyflavone-7-O-(6′′-O-p-coumaroyl)-β-d-glucopyranoside (3), have been isolated from Bidens frondosa together with fifty-three known compounds 456. The structures of these compounds were established by spectroscopic methods. mainly ESIMS, 1D- and 2D-NMR spectroscopic data. and comparison with literature data. Compounds 134, 36, 39, 43, 47, 51, and 52 were tested for inhibition of nuclear factor kappa B (NF-κB) in 293-NF-κB-luciferase report cell line induced by lipopolysaccharide (LPS), and compounds 1, 2, 3, 9, 15, 21, 24 and 51 were tested for the production of TNF-α, IL-1β, IL-6, IL-10 in RAW 264.7 macrophages induced by LPS. In conclusion, the isolated compounds 1, 2, 3, 9, 15, 21, 24 and 51 exhibited significant activity in anti-inflammatory activity assays. Full article
(This article belongs to the Section Natural Products Chemistry)
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Open AccessArticle Fluorescent Sensor for PH Monitoring Based on an i-Motif- – Switching Aptamer Containing a Tricyclic Cytosine Analogue (tC)
Molecules 2015, 20(10), 18511-18525; https://doi.org/10.3390/molecules201018511
Received: 31 August 2015 / Revised: 24 September 2015 / Accepted: 6 October 2015 / Published: 9 October 2015
Cited by 10 | Viewed by 2920 | PDF Full-text (932 KB) | HTML Full-text | XML Full-text
Abstract
There are cytosine-rich regions in the genome that bind protons with high specificity. Thus protonated C-rich sequence may undergo folding to tetraplex structures called i-motifs. Therefore, one can regard such specific C-rich oligonucleotides as aptamers that recognize protons and undergo conformational transitions. Proper [...] Read more.
There are cytosine-rich regions in the genome that bind protons with high specificity. Thus protonated C-rich sequence may undergo folding to tetraplex structures called i-motifs. Therefore, one can regard such specific C-rich oligonucleotides as aptamers that recognize protons and undergo conformational transitions. Proper labeling of the aptamer with a fluorescent tag constitutes a platform to construct a pH-sensitive aptasensor. Since the hemiprotonated C-C+ base pairs are responsible for the folded tetraplex structure of i-motif, we decided to substitute one of cytosines in an aptamer sequence with its fluorescent analogue, 1,3-diaza-2-oxophenothiazine (tC). In this paper we report on three tC-modified fluorescent probes that contain RET related sequences as a proton recognizing aptamer. Results of the circular dichroism (CD), UV absorption melting experiments, and steady-state fluorescence measurements of these tC-modified i-motif probes are presented and discussed. The pH-induced i-motif formation by the probes resulted in fluorescence quenching of tC fluorophore. Efficiency of quenching was related to the pH variations. Suitability of the sensor for monitoring pH changes was also demonstrated. Full article
(This article belongs to the Special Issue Aptamers: Past, Present, and Future)
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Open AccessArticle Highly Stable Tetra-Phenolato Titanium(IV) Agent Formulated into Nanoparticles Demonstrates Anti-Tumoral Activity and Selectivity
Molecules 2015, 20(10), 18526-18538; https://doi.org/10.3390/molecules201018526
Received: 1 September 2015 / Revised: 30 September 2015 / Accepted: 5 October 2015 / Published: 9 October 2015
Cited by 10 | Viewed by 2569 | PDF Full-text (847 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Titanium(IV) complexes exhibit high potential as anti-tumor agents, particularly due to their low intrinsic toxicity and cytotoxicity toward cisplatin resistant cells. Nevertheless, Ti(IV) complexes generally undergo rapid hydrolysis that previously hampered their utilization as anticancer drugs. We recently overcame this difficulty by developing [...] Read more.
Titanium(IV) complexes exhibit high potential as anti-tumor agents, particularly due to their low intrinsic toxicity and cytotoxicity toward cisplatin resistant cells. Nevertheless, Ti(IV) complexes generally undergo rapid hydrolysis that previously hampered their utilization as anticancer drugs. We recently overcame this difficulty by developing a highly stable Ti(IV) complex that is based on tetra-phenolato, hexadentate ligand, formulated into organic nanoparticles. Herein we investigated the activity of this complex in vitro and in vivo. Although inactive when tested directly due to poor solubility, when formulated, this complex displayed (a) high cytotoxicity toward cisplatin resistant human ovarian cells, A2780-cp, with resistance factor of 1.1; (b) additive behavior in combination with cisplatin toward ovarian and colon cancer cells; (c) selectivity toward cancer cells as implied by its mild activity toward non-cancerous, fibroblast lung cells, MRC-5; (d) high stability and durability as manifested by the ability to maintain cytotoxicity, even following one week of incubation in 100% aquatic medium solution; and (e) in vivo efficacy toward solid tumors of human colon cancer cells, HT-29, in nude mice without any clinical signs of toxicity. These features support the formulated phenolato Ti(IV) complex being an effective and selective anti-tumoral agent. Full article
(This article belongs to the collection Poorly Soluble Drugs)
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Open AccessArticle Identification and Expression Analysis of Zebrafish (Danio rerio) E-Selectin during Embryonic Development
Molecules 2015, 20(10), 18539-18550; https://doi.org/10.3390/molecules201018539
Received: 25 July 2015 / Revised: 10 September 2015 / Accepted: 25 September 2015 / Published: 12 October 2015
Cited by 2 | Viewed by 21642 | PDF Full-text (1840 KB) | HTML Full-text | XML Full-text
Abstract
In this study, we cloned the full-length cDNA of E-selectin of zebrafish (Danio rerio), analyzed its expression pattern and preliminarily explored its biological function. Zebrafish E-selectin cDNA is 3146 bp and encodes a putative 871 amino acid protein. All structural domains [...] Read more.
In this study, we cloned the full-length cDNA of E-selectin of zebrafish (Danio rerio), analyzed its expression pattern and preliminarily explored its biological function. Zebrafish E-selectin cDNA is 3146 bp and encodes a putative 871 amino acid protein. All structural domains involved in E-selectin function are conserved in the putative protein. Whole-mount in situ hybridization of zebrafish at 24 and 48 h post-fertilization (hpf) revealed E-selectin expression mainly in vascular/endothelial progenitor cells in the posterior trunk and blood cells in the intermediate cell mass and posterior cardinal vein regions. Real-time quantitative RT-PCR analysis detected E-selectin expression at 0.2, 24 and 48 hpf and significantly decreased from 48 to 72 hpf. The expression of E-selectin, tumor necrosis factor-α and interleukin-1β was significantly upregulated at 22 to 72 h after induction with bacterial lipopolysaccharide. Thus, the structure of E-selectin protein is highly conserved among species, and E-selectin may be involved in embryonic development and essential for hematopoiesis and angiogenesis during embryonic development in zebrafish. Furthermore, we provide the first evidence of inflammatory mediators inducing E-selectin expression in non-mammalian vertebrates, which suggests that zebrafish E-selectin may be involved in inflammation and probably has similar biological function to mammalian E-selectin. Full article
(This article belongs to the Section Molecular Diversity)
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Open AccessArticle Limonoids from the Seeds of Swietenia macrophylla and Their Anti-Inflammatory Activities
Molecules 2015, 20(10), 18551-18564; https://doi.org/10.3390/molecules201018551
Received: 23 August 2015 / Revised: 2 October 2015 / Accepted: 5 October 2015 / Published: 12 October 2015
Cited by 8 | Viewed by 2037 | PDF Full-text (792 KB) | HTML Full-text | XML Full-text
Abstract
A new limonoid, swietemacrophin (1), was isolated from the seeds of Swietenia macrophylla, together with five known compounds 26. The structure of 1 was determined through extensive 1D/2D-NMR and mass-spectrometric analyses. Swietemacrophin (1), humilinolide F [...] Read more.
A new limonoid, swietemacrophin (1), was isolated from the seeds of Swietenia macrophylla, together with five known compounds 26. The structure of 1 was determined through extensive 1D/2D-NMR and mass-spectrometric analyses. Swietemacrophin (1), humilinolide F (2), 3,6-O,O-diacetylswietenolide (3), 3-O-tigloylswietenolide (4), and swietemahonin E (5) exhibited inhibition (IC50 values ≤ 45.44 μM) of superoxide anion generation by human neutrophils in response to formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP). Compounds 1, 4, 5, and swietenine (6) showed potent inhibition with IC50 values ≤ 36.32 μM, against lipopolysaccharide (LPS)-induced nitric oxide (NO) generation. Full article
(This article belongs to the Section Natural Products Chemistry)
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Open AccessArticle Synthesis, Fluorescence Properties, and Antiproliferative Potential of Several 3-Oxo-3H-benzo[f]chromene-2-carboxylic Acid Derivatives
Molecules 2015, 20(10), 18565-18584; https://doi.org/10.3390/molecules201018565
Received: 1 August 2015 / Revised: 3 October 2015 / Accepted: 7 October 2015 / Published: 13 October 2015
Cited by 2 | Viewed by 2131 | PDF Full-text (1074 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In this study, two series of 3-oxo-3H-benzo[f]chromene-2-carboxylic acid derivatives (compounds 5ai and 6ag) were synthesized. Their in vitro proliferation inhibitory activities against the A549 and NCI-H460 human non-small cell lung cancer (NSCLC) cell lines [...] Read more.
In this study, two series of 3-oxo-3H-benzo[f]chromene-2-carboxylic acid derivatives (compounds 5ai and 6ag) were synthesized. Their in vitro proliferation inhibitory activities against the A549 and NCI-H460 human non-small cell lung cancer (NSCLC) cell lines were evaluated. Their photophysical properties were measured. Among these target compounds, 5e exhibited the strongest antiproliferative activity by inducing apoptosis, arresting cell cycle, and elevating intracellular reactive oxygen species (ROS) level, suggesting that it may be a potent antitumor agent. In addition, compound 6g with very low cytotoxicity, demonstrated excellent fluorescence properties, which could be used as an effective fluorescence probe for biological imaging. Full article
(This article belongs to the Section Bioorganic Chemistry)
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Open AccessArticle Green Synthesis of Novel Polyaniline Nanofibers: Application in pH Sensing
Molecules 2015, 20(10), 18585-18596; https://doi.org/10.3390/molecules201018585
Received: 19 June 2015 / Revised: 29 September 2015 / Accepted: 30 September 2015 / Published: 13 October 2015
Cited by 9 | Viewed by 2508 | PDF Full-text (1837 KB) | HTML Full-text | XML Full-text
Abstract
An optically active polyaniline nanomaterial (PANI-Nap), doped with (S)-naproxen, was developed and evaluated as a potent pH sensor. We synthesized the material in one pot by the addition of the dopant, (S)-naproxen, prior to polymerization, followed by the addition [...] Read more.
An optically active polyaniline nanomaterial (PANI-Nap), doped with (S)-naproxen, was developed and evaluated as a potent pH sensor. We synthesized the material in one pot by the addition of the dopant, (S)-naproxen, prior to polymerization, followed by the addition of the oxidizing agent (ammonium persulfate) that causes polymerization of the aniline. This green chemistry approach allowed us to take only 1 h to produce a water-soluble and stable nanomaterial. UV-visible spectroscopy, fluorescence spectroscopy, FT-IR spectroscopy, Raman spectroscopy, scanning electron microscopy (SEM), transmission electron microscopy (TEM), and X-ray photoelectron spectroscopy (XPS) were used to characterize the designed nanomaterial. This nanomaterial exhibited excellent pH sensing properties and showed long term stability (up to one month) without loss of sensor performance. Full article
(This article belongs to the Special Issue Frontier in Green Chemistry Approaches)
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Open AccessArticle Qualitative and Quantitative Analysis of the Major Constituents in Shexiang Tongxin Dropping Pill by HPLC-Q-TOF-MS/MS and UPLC-QqQ-MS/MS
Molecules 2015, 20(10), 18597-18619; https://doi.org/10.3390/molecules201018597
Received: 17 July 2015 / Revised: 23 September 2015 / Accepted: 6 October 2015 / Published: 14 October 2015
Cited by 18 | Viewed by 2622 | PDF Full-text (1131 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Shexiang Tongxin dropping pill (STP) is a traditional Chinese medicine formula that consists of total saponins of ginseng, synthetic Calculus bovis, bear gall, Venenum bufonis, borneol and Salvia miltiorrhiza. STP has been widely used in China and Southeast Asia for [...] Read more.
Shexiang Tongxin dropping pill (STP) is a traditional Chinese medicine formula that consists of total saponins of ginseng, synthetic Calculus bovis, bear gall, Venenum bufonis, borneol and Salvia miltiorrhiza. STP has been widely used in China and Southeast Asia for the treatment of cardiovascular diseases. In this study, a qualitative analytical method using high performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry was developed for identification of the major constituents in STP. Based on the retention time and MS spectra, 41 components were identified by comparison with reference compounds and literature data. Moreover, using ultra-performance liquid chromatography coupled with triple-quadrupole tandem mass spectrometry in multiple-reaction monitoring mode, we quantified 13 of the identified constituents (ginsenoside Rg1, ginsenoside Rk3, cinobufagin, arenobufagin, bufalin, resibufogenin, tanshinone IIA, taurine, tauroursodeoxycholic acid, taurocholic acid, cholic acid, deoxycholic acid, and chenodeoxycholic acid). These results suggest that this new approach is applicable for the routine analysis and quality control of STP products and provides fundamental data for further in vivo pharmacokinetical studies. Full article
(This article belongs to the Section Metabolites)
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Open AccessArticle Resin-Immobilized Palladium Nanoparticle Catalysts for Organic Reactions in Aqueous Media: Morphological Aspects
Molecules 2015, 20(10), 18661-18684; https://doi.org/10.3390/molecules201018661
Received: 24 September 2015 / Revised: 8 October 2015 / Accepted: 8 October 2015 / Published: 14 October 2015
Cited by 9 | Viewed by 2434 | PDF Full-text (12768 KB) | HTML Full-text | XML Full-text
Abstract
An insight into the nano- and micro-structural morphology of a polymer supported Pd catalyst employed in different catalytic reactions under green conditions is reported. The pre-catalyst was obtained by copolymerization of the metal-containing monomer Pd(AAEMA)2 [AAEMA = deprotonated form of 2-(acetoacetoxy) [...] Read more.
An insight into the nano- and micro-structural morphology of a polymer supported Pd catalyst employed in different catalytic reactions under green conditions is reported. The pre-catalyst was obtained by copolymerization of the metal-containing monomer Pd(AAEMA)2 [AAEMA = deprotonated form of 2-(acetoacetoxy) ethyl methacrylate] with ethyl methacrylate as co-monomer, and ethylene glycol dimethacrylate as cross-linker. This material was used in water for the Suzuki-Miyaura cross-coupling of aryl bromides, and for the reduction of nitroarenes and quinolines using NaBH4 or H2, as reductants. TEM analyses showed that in all cases the pristine Pd(II) species were reduced in situ to Pd(0), which formed metal nanoparticles (NPs, the real active species). The dependence of their average size (2–10 nm) and morphology on different parameters (temperature, reducing agent, presence of a phase transfer agent) is discussed. TEM and micro-IR analyses showed that the polymeric support retained its porosity and stability for several catalytic cycles in all reactions and Pd NPs did not aggregate after reuse. The metal nanoparticle distribution throughout the polymer matrix after several recycles provided precious information about the catalytic mechanism, which was truly heterogeneous in the hydrogenation reactions and of the so-called “release and catch” type in the Suzuki coupling. Full article
(This article belongs to the Special Issue Metal Nanocatalysts in Green Synthesis and Energy Applications)
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Open AccessArticle Antimicrobial Activity of Rhoeo discolor Phenolic Rich Extracts Determined by Flow Cytometry
Molecules 2015, 20(10), 18685-18703; https://doi.org/10.3390/molecules201018685
Received: 5 August 2015 / Revised: 7 September 2015 / Accepted: 18 September 2015 / Published: 14 October 2015
Cited by 5 | Viewed by 3251 | PDF Full-text (2836 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Traditional medicine has led to the discovery of important active substances used in several health-related areas. Phytochemicals in Rhoeo discolor extracts have proven to have important antimicrobial activity. In the present study, our group determined the antimicrobial effects of extracts of Rhoeo discolor [...] Read more.
Traditional medicine has led to the discovery of important active substances used in several health-related areas. Phytochemicals in Rhoeo discolor extracts have proven to have important antimicrobial activity. In the present study, our group determined the antimicrobial effects of extracts of Rhoeo discolor, a plant commonly used in Mexico for both medicinal and ornamental purposes. We evaluated the in vitro activity of phenolic rich extracts against specifically chosen microorganisms of human health importance by measuring their susceptibility via agar-disc diffusion assay and flow cytometry: Gram-positive Listeria innocua and Streptococcus mutans, Gram-negative Escherichia coli and Pseudomonas aeruginosa, and lastly a fungal pathogen Candida albicans. Ten different extracts were tested in eight different doses on all the microorganisms. Analytical data revealed a high content of phenolic compounds. Both agar-disc diffusion assay and flow cytometry results demonstrated that Pseudomonas aeruginosa was the least affected by extract exposure. However, low doses of these extracts (predominantly polar), in a range from 1 to 4 μg/mL, did produce a statistically significant bacteriostatic and bactericidal effect on the rest of the microorganisms. These results suggest the addition of certain natural extracts from Rhoeo discolor could act as antibacterial and antimycotic drugs or additives for foods and cosmetics. Full article
(This article belongs to the Special Issue Recent Advances in Plant Phenolics)
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Open AccessArticle Study of the Biotransformation of Tongmai Formula by Human Intestinal Flora and Its Intestinal Permeability across the Caco-2 Cell Monolayer
Molecules 2015, 20(10), 18704-18716; https://doi.org/10.3390/molecules201018704
Received: 23 August 2015 / Revised: 2 October 2015 / Accepted: 7 October 2015 / Published: 15 October 2015
Cited by 10 | Viewed by 2485 | PDF Full-text (743 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Tongmai formula (TMF) is a well-known Chinese medicinal preparation that contains isoflavones as its major bioactive constituents. As traditional Chinese medicines (TCMs) are usually used by oral administration, their fate inside the intestinal lumen, including their biotransformation by human intestinal flora (HIF) and [...] Read more.
Tongmai formula (TMF) is a well-known Chinese medicinal preparation that contains isoflavones as its major bioactive constituents. As traditional Chinese medicines (TCMs) are usually used by oral administration, their fate inside the intestinal lumen, including their biotransformation by human intestinal flora (HIF) and intestinal absorption deserves study. In this work TMF extract was incubated with human intestinal bacteria under anaerobic conditions and the changes in the twelve main constituents of TMF were then investigated. Their intestinal permeabilities, i.e., the transport capability across the intestinal brush border were investigated with a human colon carcinoma cell line (Caco­2) cell monolayer model to predict the absorption mechanism. Meanwhile, rapid HPLC-DAD methods were established for the assay. According to the biotransformation curves of the twelve constituents and the permeability coefficients, the intestinal absorption capacity of the typical compounds was elevated from the levels of 10−7 cm/s to 10−5 cm/s from those of the original compounds in TMF. Among them the main isoflavone glycosides puerarin (4), mirificin (6) and daidzin (7) were transformed into the same aglycone, daidzein (10). Therefore it was predicted that the aglycone compounds might be the real active ingredients in TMF. The models used can represent a novel path for the TCM studies. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Enzymatic Hydrolysis and Simultaneous Extraction for Preparation of Genipin from Bark of Eucommia ulmoides after Ultrasound, Microwave Pretreatment
Molecules 2015, 20(10), 18717-18731; https://doi.org/10.3390/molecules201018717
Received: 10 July 2015 / Revised: 22 September 2015 / Accepted: 12 October 2015 / Published: 15 October 2015
Cited by 4 | Viewed by 1872 | PDF Full-text (2265 KB) | HTML Full-text | XML Full-text
Abstract
A continuous process based on the combination of ultrasounds and/or microwaves pretreatments followed by enzymatic hydrolysis and simultaneous extraction (EHSE) has been proposed to recover genipin from Eucommia ulmoides bark. At first, in the pretreatment step, the mixture of 1.0 g dried bark [...] Read more.
A continuous process based on the combination of ultrasounds and/or microwaves pretreatments followed by enzymatic hydrolysis and simultaneous extraction (EHSE) has been proposed to recover genipin from Eucommia ulmoides bark. At first, in the pretreatment step, the mixture of 1.0 g dried bark powder and 10 mL deionized water were irradiated by microwave under 500 W for 10 min. Then, in hydrolysis step, the optimal conditions were as follows: 0.5 mg/mL of cellulase concentration, 4.0 pH of enzyme solution, 24 h of incubation time and 40 °C of incubation temperature. After incubation, 10 mL ethanol was added to extract genipin for 30 min by ultrasound. After EHSE treatment, the yield of genipin could reach 1.71 μmol/g. Moreover, scanning electron micrographs illustrated that severe structural disruption of plant was obtained by EHSE. The results indicated that the EHSE method provided a good alternative for the preparation of genipin from Eucommia ulmoides bark as well as other herbs. Full article
(This article belongs to the Section Natural Products Chemistry)
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Open AccessArticle In Vitro Cytoprotective Effects and Antioxidant Capacity of Phenolic Compounds from the Leaves of Swietenia macrophylla
Molecules 2015, 20(10), 18777-18788; https://doi.org/10.3390/molecules201018777
Received: 16 July 2015 / Revised: 18 August 2015 / Accepted: 25 August 2015 / Published: 16 October 2015
Cited by 5 | Viewed by 2027 | PDF Full-text (900 KB) | HTML Full-text | XML Full-text
Abstract
Swietenia macrophylla (mahogany) is a highly valued timber species, whereas the leaves are considered to be waste product. A total of 27 phenolic compounds were identified in aqueous extracts from mahogany leaves by comparing retention times and mass spectra data with those of [...] Read more.
Swietenia macrophylla (mahogany) is a highly valued timber species, whereas the leaves are considered to be waste product. A total of 27 phenolic compounds were identified in aqueous extracts from mahogany leaves by comparing retention times and mass spectra data with those of authentic standards using LC-ESI-MS/MS. Polyphenols play an important role in plants as defense mechanisms against pests and pathogens and have potent antioxidant properties. In terms of health applications, interest has increased considerably in naturally occurring antioxidant sources, since they can retard the progress of many important neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases. The antioxidant capacities of two aqueous extracts, M1 (decoction) and M2 (infusion), were measured using TEAC and Folin-Ciocalteau methods. Additionally, M1 was used in order to investigate its potential cytoprotective effects on an in vitro model of neurodegeneration, by using primary cerebellar cultures exposed to methyl mercury (MeHg). Under experimental sub-chronic conditions (72 h), concomitant exposure of the same cultures to MeHg and M1 extract resulted in a statistically significant increase in cell viability in all three concentrations tested (10, 50 and 100 μg/mL), strongly suggesting that due to its high content of antioxidant compounds, the M1 extract provides significant cytoprotection against the MeHg-induced in vitro neurotoxicity. Full article
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Open AccessArticle Phosphonylated Acyclic Guanosine Analogues with the 1,2,3-Triazole Linker
Molecules 2015, 20(10), 18789-18807; https://doi.org/10.3390/molecules201018789
Received: 1 September 2015 / Revised: 15 September 2015 / Accepted: 17 September 2015 / Published: 16 October 2015
Cited by 4 | Viewed by 2202 | PDF Full-text (834 KB) | HTML Full-text | XML Full-text
Abstract
A novel series of {4-[(2-amino-6-chloro-9H-purin-9-yl)methyl]-1H-1,2,3-triazol-1-yl}alkylphosphonates and {4-[(2-amino-6-oxo-1,6-dihydro-9H-purin-9-yl)methyl]-1H-1,2,3-triazol-1-yl}alkylphosphonates as acyclic analogues of guanosine were synthesized and assessed for antiviral activity against a broad range of DNA and RNA viruses and for their cytostatic activity toward three [...] Read more.
A novel series of {4-[(2-amino-6-chloro-9H-purin-9-yl)methyl]-1H-1,2,3-triazol-1-yl}alkylphosphonates and {4-[(2-amino-6-oxo-1,6-dihydro-9H-purin-9-yl)methyl]-1H-1,2,3-triazol-1-yl}alkylphosphonates as acyclic analogues of guanosine were synthesized and assessed for antiviral activity against a broad range of DNA and RNA viruses and for their cytostatic activity toward three cancerous cell lines (HeLa, L1210 and CEM). They were devoid of antiviral activity; however, several phosphonates were found slightly cytostatic against HeLa cells at an IC50 in the 80–210 µM range. Compounds (1R,2S)-17k and (1S,2S)-17k showed the highest inhibitory effects (IC50 = 15–30 µM) against the proliferation of murine leukemia (L1210) and human T-lymphocyte (CEM) cell lines. Full article
(This article belongs to the Section Organic Chemistry)
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Open AccessArticle Synthesis, Hydrolysis, and Protonation-Promoted Intramolecular Reductive Breakdown of Potential NRTIs: Stavudine α-P-Borano-γ-P-N-l-tryptophanyltriphosphates
Molecules 2015, 20(10), 18808-18826; https://doi.org/10.3390/molecules201018808
Received: 16 August 2015 / Revised: 15 September 2015 / Accepted: 21 September 2015 / Published: 16 October 2015
Cited by 3 | Viewed by 2072 | PDF Full-text (968 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Phosphorus-modified prodrugs of dideoxynucleoside triphosphates (ddNTPs) have shown promise as pronucleotide strategies for improving antiviral activity compared to their parent dideoxynucleosides. Borane modified NTPs offer a promising choice as nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs). However, the availability of α-P-borano-γ-P-substituted [...] Read more.
Phosphorus-modified prodrugs of dideoxynucleoside triphosphates (ddNTPs) have shown promise as pronucleotide strategies for improving antiviral activity compared to their parent dideoxynucleosides. Borane modified NTPs offer a promising choice as nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs). However, the availability of α-P-borano-γ-P-substituted NTP analogs remains limited due to challenges with synthesis and purification. Here, we report the chemical synthesis and stability of a new potential class of NRTI prodrugs: stavudine (d4T) 5′-α-P-borano-γ-P-N-L-tryptophanyltriphosphates. One-pot synthesis of these compounds was achieved via a modified cyclic trimetaphosphate approach. Pure Rp and Sp diastereomers were obtained after HPLC separation. Based on LC-MS analysis, we report degradation pathways, half-lives (5–36 days) and mechanisms arising from structural differences to generate the corresponding borano tri- and di-phosphates, and H-phosphonate, via several parallel routes in buffer at physiologically relevant pH and temperature. Here, the major hydrolysis products, d4T α-P-boranotriphosphate Rp and Sp isomers, were isolated by HPLC and identified with spectral data. We first propose that one of the major degradation products, d4T H-phosphonate, was generated from the d4T pronucleotides via a protonation-promoted intramolecular reduction followed by a second step nucleophilic attack. This report could provide valuable information for pronucleotide-based drug design in terms of selective release of target nucleotides. Full article
(This article belongs to the Special Issue Frontiers in Nucleic Acid Chemistry)
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Open AccessArticle Synthesis and Crystallographic Insight into the Structural Aspects of Some Novel Adamantane-Based Ester Derivatives
Molecules 2015, 20(10), 18827-18846; https://doi.org/10.3390/molecules201018827
Received: 24 August 2015 / Revised: 31 August 2015 / Accepted: 5 October 2015 / Published: 16 October 2015
Cited by 4 | Viewed by 2232 | PDF Full-text (3079 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Adamantyl-based compounds are commercially important in the treatments for neurological conditions and type-2 diabetes, aside from their anti-viral abilities. Their values in drug design are chronicled as multi-dimensional. In the present study, a series of 2-(adamantan-1-yl)-2-oxoethyl benzoates, 2(aq), [...] Read more.
Adamantyl-based compounds are commercially important in the treatments for neurological conditions and type-2 diabetes, aside from their anti-viral abilities. Their values in drug design are chronicled as multi-dimensional. In the present study, a series of 2-(adamantan-1-yl)-2-oxoethyl benzoates, 2(aq), and 2-(adamantan-1-yl)-2-oxoethyl 2-pyridinecarboxylate, 2r, were synthesized by reacting 1-adamantyl bromomethyl ketone with various carboxylic acids using potassium carbonate in dimethylformamide medium at room temperature. Three-dimensional structures studied using X-ray diffraction suggest that the adamantyl moiety can serve as an efficient building block to synthesize 2-oxopropyl benzoate derivatives with synclinal conformation with a looser-packed crystal packing system. Compounds 2a, 2b, 2f, 2g, 2i, 2j, 2m, 2n, 2o, 2q and 2r exhibit strong antioxidant activities in the hydrogen peroxide radical scavenging test. Furthermore, three compounds, 2p, 2q and 2r, show good anti-inflammatory activities in the evaluation of albumin denaturation. Full article
(This article belongs to the Section Molecular Diversity)
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Open AccessCommunication Amine-Functionalized ZnO Nanosheets for Efficient CO2 Capture and Photoreduction
Molecules 2015, 20(10), 18847-18855; https://doi.org/10.3390/molecules201018847
Received: 20 August 2015 / Revised: 7 October 2015 / Accepted: 14 October 2015 / Published: 16 October 2015
Cited by 15 | Viewed by 2385 | PDF Full-text (1773 KB) | HTML Full-text | XML Full-text
Abstract
Amine-functionalized ZnO nanosheets were prepared through a one-step hydrothermal method by using monoethanolamine, which has a hydroxyl group, for covalent attachment on ZnO and a primary amine group to supply the amine-functionalization. We demonstrate that the terminal amine groups on ZnO surfaces substantially [...] Read more.
Amine-functionalized ZnO nanosheets were prepared through a one-step hydrothermal method by using monoethanolamine, which has a hydroxyl group, for covalent attachment on ZnO and a primary amine group to supply the amine-functionalization. We demonstrate that the terminal amine groups on ZnO surfaces substantially increase the capability of CO2 capture via chemisorption, resulting in effective CO2 activation. As a result, the photogenerated electrons from excited ZnO can more readily reduce the surface-activated CO2, which thereby enhances the activity for photocatalytic CO2 reduction. Full article
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Open AccessArticle Maleimides Designed for Self-Assembly and Reactivity on Graphene
Molecules 2015, 20(10), 18856-18869; https://doi.org/10.3390/molecules201018856
Received: 26 August 2015 / Revised: 12 October 2015 / Accepted: 13 October 2015 / Published: 16 October 2015
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Abstract
Two new maleimide derivatives have been synthesized, prone to self-assemble and react with graphene as dienophiles. Both compounds bear a long alkyl chain on the carbon-carbon double bond position 3. The maleimide 1 bears a second alkyl chain at the nitrogen, while in [...] Read more.
Two new maleimide derivatives have been synthesized, prone to self-assemble and react with graphene as dienophiles. Both compounds bear a long alkyl chain on the carbon-carbon double bond position 3. The maleimide 1 bears a second alkyl chain at the nitrogen, while in compound 2, three maleimide functionalities are linked to a triethynylbenzene core. Full article
(This article belongs to the Section Organic Chemistry)
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Open AccessArticle Structure–Activity Relationship of Oligomeric Flavan-3-ols: Importance of the Upper-Unit B-ring Hydroxyl Groups in the Dimeric Structure for Strong Activities
Molecules 2015, 20(10), 18870-18885; https://doi.org/10.3390/molecules201018870
Received: 30 June 2015 / Revised: 3 October 2015 / Accepted: 7 October 2015 / Published: 16 October 2015
Cited by 8 | Viewed by 2126 | PDF Full-text (1083 KB) | HTML Full-text | XML Full-text
Abstract
Proanthocyanidins, which are composed of oligomeric flavan-3-ol units, are contained in various foodstuffs (e.g., fruits, vegetables, and drinks) and are strongly biologically active compounds. We investigated which element of the proanthocyanidin structure is primarily responsible for this functionality. In this study, we elucidate [...] Read more.
Proanthocyanidins, which are composed of oligomeric flavan-3-ol units, are contained in various foodstuffs (e.g., fruits, vegetables, and drinks) and are strongly biologically active compounds. We investigated which element of the proanthocyanidin structure is primarily responsible for this functionality. In this study, we elucidate the importance of the upper-unit of 4–8 condensed dimeric flavan-3-ols for antimicrobial activity against Saccharomyces cerevisiae (S. cerevisiae) and cervical epithelioid carcinoma cell line HeLa S3 proliferation inhibitory activity. To clarify the important constituent unit of proanthocyanidin, we synthesized four dimeric compounds, (−)-epigallocatechin-[4,8]-(+)-catechin, (−)-epigallocatechin-[4,8]-(−)-epigallocatechin, (−)-epigallocatechin-[4,8]-(−)-epigallocatechin-3-O-gallate, and (+)-catechin-[4,8]-(−)-epigallocatechin and performed structure–activity relationship (SAR) studies. In addition to antimicrobial activity against S. cerevisiae and proliferation inhibitory activity on HeLa S3 cells, the correlation of 2,2-diphenyl-l-picrylhydrazyl radical scavenging activity with the number of phenolic hydroxyl groups was low. On the basis of the results of our SAR studies, we concluded that B-ring hydroxyl groups of the upper-unit of the dimer are crucially important for strong and effective activity. Full article
(This article belongs to the Section Natural Products Chemistry)
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Open AccessArticle Phytochemicals from Ruta graveolens Activate TAS2R Bitter Taste Receptors and TRP Channels Involved in Gustation and Nociception
Molecules 2015, 20(10), 18907-18922; https://doi.org/10.3390/molecules201018907
Received: 22 July 2015 / Revised: 26 August 2015 / Accepted: 9 October 2015 / Published: 16 October 2015
Cited by 13 | Viewed by 2961 | PDF Full-text (1262 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Ruta graveolens (rue) is a spontaneous plant in the Mediterranean area with a strong aroma and a very intense bitter taste, used in gastronomy and in folk medicine. From the leaves, stems and fruits of rue, we isolated rutin, rutamarin, three furanocoumarins, two [...] Read more.
Ruta graveolens (rue) is a spontaneous plant in the Mediterranean area with a strong aroma and a very intense bitter taste, used in gastronomy and in folk medicine. From the leaves, stems and fruits of rue, we isolated rutin, rutamarin, three furanocoumarins, two quinolinic alkaloids, a dicoumarin and two long chain ketones. Bitter taste and chemesthetic properties have been evaluated by in vitro assays with twenty receptors of the TAS2R family and four TRP ion channels involved in gustation and nociception. Among the alkaloids, skimmianine was active as a specific agonist of T2R14, whereas kokusaginin did not activate any of the tested receptors. The furanocoumarins activates TAS2R10, 14, and 49 with different degrees of selectivity, as well as the TRPA1 somatosensory ion channel. Rutamarin is an agonist of TRPM5 and TRPV1 and a strong antagonist of TRPM8 ion channels. Full article
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Open AccessArticle Effect of Three Training Systems on Grapes in a Wet Region of China: Yield, Incidence of Disease and Anthocyanin Compositions of Vitis vinifera cv. Cabernet Sauvignon
Molecules 2015, 20(10), 18967-18987; https://doi.org/10.3390/molecules201018967
Received: 22 August 2015 / Revised: 9 October 2015 / Accepted: 12 October 2015 / Published: 19 October 2015
Cited by 6 | Viewed by 1918 | PDF Full-text (1510 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Grapevine training systems determine the suitability for grape varieties in a specific growing region. We evaluated the influence of three training systems, Single Guyot (SG), Spur-pruned Vertical Shoot-Positioned (VSP), and Four-Arm Kniffin (4AK), on the performance of grapes and vines of Vitis vinifera [...] Read more.
Grapevine training systems determine the suitability for grape varieties in a specific growing region. We evaluated the influence of three training systems, Single Guyot (SG), Spur-pruned Vertical Shoot-Positioned (VSP), and Four-Arm Kniffin (4AK), on the performance of grapes and vines of Vitis vinifera L. cv. Cabernet Sauvignon in the 2012 and 2013 growing seasons in a wet region of central China. 4AK was the most productive system in comparison to SG and VSP. SG and VSP had lower disease infections of leaves and berries, especially in the mid- and final stage of berry ripening. Three training systems had no impact on berry maturity. PLS-DA (Partial Least Squares-Discriminant) analysis showed that the relatively dry vintage could well discriminate three training systems, but the wet vintage was not. A wet vintage of 2013 had more accumulation of 3′5′-substituted and acylated anthocyanins, including malvidin-3-O-(6-O-acetyl)-glucoside, malvidin-3-O-glucoside, and petunidin-3-O-(cis-6-O-coumaryl)-glucoside, etc. With regard to the effect of training systems, 4AK grapes had the lowest concentrations of total anthocyanins and individual anthocyanins, SG and VSP differed according to the different vintages, and showed highest concentration of total individual anthocyanins in 2012 and 2013, respectively. Generally, VSP benefited the most, contributing to significantly highest levels of total individual anthocyanins, and major anthocyanin, including malvidin-3-O-glucoside and malvidin-3-O-(6-O-acetyl)-glucoside, and the grapes obtained from VSP presented significantly highest proportion of 3′5′-substituted anthocyanins. With regard to the ratios of 3′5′/3′-substituted, methoxylated/non-methoxylated and acylated/non-acylated anthocyanins, the significantly higher levels were also shown in VSP system. In summary, VSP was the best training system for Cabernet Sauvignon to accumulate relatively stable individual anthocyanins in this wet region of China and potentially in other rainy regions. Full article
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Open AccessArticle Validated LC-MS/MS Method for the Determination of Scopoletin in Rat Plasma and Its Application to Pharmacokinetic Studies
Molecules 2015, 20(10), 18988-19001; https://doi.org/10.3390/molecules201018988
Received: 18 September 2015 / Revised: 12 October 2015 / Accepted: 13 October 2015 / Published: 19 October 2015
Cited by 7 | Viewed by 2404 | PDF Full-text (1577 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A rapid, sensitive and selective liquid chromatography-electrospray ionization-tandem mass spectrometric method was developed and validated for the quantification of scopoletin in rat plasma. After the addition of the internal standard xanthotoxin, plasma samples were pretreated by a simple one-step protein precipitation with acetonitrile-methanol [...] Read more.
A rapid, sensitive and selective liquid chromatography-electrospray ionization-tandem mass spectrometric method was developed and validated for the quantification of scopoletin in rat plasma. After the addition of the internal standard xanthotoxin, plasma samples were pretreated by a simple one-step protein precipitation with acetonitrile-methanol (2:1, v/v). Chromatographic separation was achieved on a Diamonsil ODS chromatography column using gradient elution with the mobile phase consisting of acetonitrile and 0.1% formic acid. The determination was performed by positive ion electrospray ionization in multiple reaction monitoring mode. The calibration curve was linear over the concentration range of 5–1000 ng/mL (r = 0.9996). The intra- and inter-day precision (RSD%) was less than 6.1%, and the accuracy (RE%) was from −3.0%–2.5%. This method was successfully applied to the pharmacokinetic research of scopoletin in rats after intravenous (5 mg/kg) or oral (5, 10 and 20 mg/kg) administration. The result showed that oral bioavailability with a dose of 5 mg/kg was 6.62% ± 1.72%, 10 mg/kg, 5.59% ± 1.16%, and 20 mg/kg, 5.65% ± 0.75%. Full article
(This article belongs to the Special Issue Coumarins, Xanthones and Related Compounds)
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Open AccessArticle The Occurrence of Propyl Lactate in Chinese Baijius (Chinese Liquors) Detected by Direct Injection Coupled with Gas Chromatography-Mass Spectrometry
Molecules 2015, 20(10), 19002-19013; https://doi.org/10.3390/molecules201019002
Received: 1 September 2015 / Revised: 7 October 2015 / Accepted: 13 October 2015 / Published: 19 October 2015
Cited by 7 | Viewed by 2111 | PDF Full-text (1106 KB) | HTML Full-text | XML Full-text
Abstract
As one of the oldest distillates in the world, flavor compounds of Chinese Baijiu (Chinese liquor) were extremely complex. Propyl lactate was firstly detected by direct injection and gas chromatography-mass spectrometry (GC-MS) in 72 Chinese Baijius. The objectives were to detect the contents [...] Read more.
As one of the oldest distillates in the world, flavor compounds of Chinese Baijiu (Chinese liquor) were extremely complex. Propyl lactate was firstly detected by direct injection and gas chromatography-mass spectrometry (GC-MS) in 72 Chinese Baijius. The objectives were to detect the contents of propyl lactate and evaluate its contribution to the aroma of Chinese Baijiu based on odor activity values (OAVs). The levels of propyl lactate in these distillates were determined by internal standard method and selective ion monitoring (SIM), which ranged from 0.050 to 1.900 mg∙L−1 under investigation. Its detection threshold was determined by Three-Alternative Forced-Choice (3-AFC) and curve fitting (CF), which was 0.740 mg∙L−1 in 38% ethanol solution. The contribution of propyl lactate on the aroma of these distillate drinks was evaluated by their odor activity values (OAVs), which varied from 0.066 to 4.440. The OAVs of propyl lactate were found to exceed 1 in 13 Chinese Baijius, including 50° Jingzhi Guniang 5 years (4.440), 52° Jingzhi Guniang 10 years (3.024), Jingyanggang (2.568), Xianghe Ronghe Shaofang (2.313), and 1956 Laolang (1.431), which indicated that propyl lactate was one of odor-active components in these Chinese Baijius. Full article
(This article belongs to the collection Recent Advances in Flavors and Fragrances)
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Open AccessArticle Oligomeric Procyanidins Interfere with Glycolysis of Activated T Cells. A Novel Mechanism for Inhibition of T Cell Function
Molecules 2015, 20(10), 19014-19026; https://doi.org/10.3390/molecules201019014
Received: 13 August 2015 / Revised: 3 October 2015 / Accepted: 15 October 2015 / Published: 20 October 2015
Cited by 3 | Viewed by 2565 | PDF Full-text (973 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Procyanidins, which are flavonoids that are found in a variety of plant species, reduce or prevent immune disorders, such as allergy and autoimmune diseases, through an unknown mechanism. In the present study, we investigated the effects of procyanidins on the T cell receptor [...] Read more.
Procyanidins, which are flavonoids that are found in a variety of plant species, reduce or prevent immune disorders, such as allergy and autoimmune diseases, through an unknown mechanism. In the present study, we investigated the effects of procyanidins on the T cell receptor (TCR)-mediated responses of CD4+ T cells in vitro. Apple procyanidins strongly suppressed the proliferation of splenic CD4+ T cells that were stimulated by an anti-CD3ε antibody, as well as splenocytes stimulated by antigen, but did not alter interleukin (IL)-2 secretion from these cells. Furthermore, we found that oligomeric procyanidins strongly suppressed, in a degree of polymerization dependent manner, the proliferation of activated CD4+ T cells, as well as their production of effector cytokines, including glycolysis associated-cytokines, without affecting IL-2 secretion. Additionally, we investigated the inhibitory effects of oligomeric procyanidins on the glycolytic activity of activated CD4+ T cells. We show that pentameric procyanidin suppressed L-lactate production and glucose uptake in activated CD4+ T cells. These results suggest that oligomeric procyanidins suppress the functions of activated CD4+ T cells by interfering with glycolysis. Full article
(This article belongs to the Section Natural Products Chemistry)
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Open AccessArticle miRNA Stability in Frozen Plasma Samples
Molecules 2015, 20(10), 19030-19040; https://doi.org/10.3390/molecules201019030
Received: 24 July 2015 / Revised: 9 October 2015 / Accepted: 13 October 2015 / Published: 20 October 2015
Cited by 25 | Viewed by 3693 | PDF Full-text (729 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
MicroRNAs (miRNAs) represent a family of small non-coding ribonucleic acids that post-transcriptionally inhibits the expression of their target messenger RNAs (mRNAs), thereby acting as general gene repressors. In this study we examined the relative quantity and stability of miRNA subjected to a long [...] Read more.
MicroRNAs (miRNAs) represent a family of small non-coding ribonucleic acids that post-transcriptionally inhibits the expression of their target messenger RNAs (mRNAs), thereby acting as general gene repressors. In this study we examined the relative quantity and stability of miRNA subjected to a long period of freezing; we compared the stability of eight miRNAs in the plasma of five human healthy controls before freezing and after six and 12 months of storage at −80 °C. In addition, we examined the plasma frozen for 14 years and the amount of miRNA still available. Using a Life Technologies protocol to amplify and quantify plasma miRNAs from EDTA (Ethylene Diamine Tetraacetic Acid)-treated blood, we analyzed the stability of eight miRNAs, (miR-125b-5p, miR-425-5p, miR-200b-5p, miR-200c-3p, miR-579-3p, miR-212-3p, miR-126-3p, and miR-21-5p). The miRNAs analyzed showed a high stability and long frozen half-life. Full article
(This article belongs to the Section Molecular Diversity)
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Open AccessArticle Thermal Influence of CNT on the Polyamide 12 Nanocomposite for Selective Laser Sintering
Molecules 2015, 20(10), 19041-19050; https://doi.org/10.3390/molecules201019041
Received: 17 September 2015 / Revised: 2 October 2015 / Accepted: 14 October 2015 / Published: 20 October 2015
Cited by 22 | Viewed by 2200 | PDF Full-text (1551 KB) | HTML Full-text | XML Full-text
Abstract
The thermal influence of carbon nanotubes (CNTs) on the PA12 in the laser sintering process was assessed by physical experiments and a three dimensional simulation model. It appears that, by adding the CNTs into the PA12 matrix, the thermal conductivity increased. A double [...] Read more.
The thermal influence of carbon nanotubes (CNTs) on the PA12 in the laser sintering process was assessed by physical experiments and a three dimensional simulation model. It appears that, by adding the CNTs into the PA12 matrix, the thermal conductivity increased. A double ellipsoidal heat flux model was applied to input a three dimensional, continuous moving, volumetric laser heat source. The predicted three dimensional temperature distributions suggested that the laser heat was conducted wider and deeper in the PA12-CNT sample than PA12. Greater heat conduction can reduce the interspace between two successive layers, and result in the increase of the parts’ density and properties. Full article
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Open AccessArticle Antioxidant Properties of Essential Oil Extracted from Pinus morrisonicola Hay Needles by Supercritical Fluid and Identification of Possible Active Compounds by GC/MS
Molecules 2015, 20(10), 19051-19065; https://doi.org/10.3390/molecules201019051
Received: 11 August 2015 / Revised: 11 October 2015 / Accepted: 15 October 2015 / Published: 20 October 2015
Cited by 6 | Viewed by 2474 | PDF Full-text (2302 KB) | HTML Full-text | XML Full-text
Abstract
Pine (Pinus morrisonicola Hay, PM) needles have been used as folk medicine for their antihypertension and lipid-lowering effects. As supercritical fluid extraction (SFE) is considered an ideal technique for the extraction of essential oil from plant materials, the present work investigated the [...] Read more.
Pine (Pinus morrisonicola Hay, PM) needles have been used as folk medicine for their antihypertension and lipid-lowering effects. As supercritical fluid extraction (SFE) is considered an ideal technique for the extraction of essential oil from plant materials, the present work investigated the optimal SFE conditions and the protective effects of different resulting fractions of PM needles on lipid peroxidation and foam cell production in macrophages. Nine PM needle extracts (PME1–9) were obtained in 1%–4% yields using different SFE conditions, of which PME1 had the lowest yield (1.1%) and PME3 the highest (3.9%). PME3 exhibited lower cytotoxic effects and stronger inhibition of lipid peroxidation and formation of foam cell in RAW 264.7 macrophages than those of other PME extracts. PME3-1 purified from PME3 by column and thin layer chromatography inhibited LDL oxidation more effectively than did PME3 in a cell-free system oxidized by Cu2+. PME3-1 dose-dependently (25–100 μg/mL) decreased conjugated diene levels and foam cell formation induced by ox-LDL. GC/MS analyses revealed that 1-docosene, neophytadiene, and methyl abietate were increased 5.2-, 1.7- and 4.3-fold in PME3-1 relative to PME3. A new hydrocarbon compound, cedrane-8,13-diol, was identified in PME3-1. Overall, the present study demonstrates the optimal extraction conditions of SFE of PM and identifies the most potent antioxidant fractions and possible active compounds in PM. Full article
(This article belongs to the collection Bioactive Compounds)
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Open AccessArticle Synthesis and Evaluation of New Pyrazoline Derivatives as Potential Anticancer Agents
Molecules 2015, 20(10), 19066-19084; https://doi.org/10.3390/molecules201019066
Received: 17 August 2015 / Revised: 14 October 2015 / Accepted: 14 October 2015 / Published: 20 October 2015
Cited by 22 | Viewed by 3049 | PDF Full-text (540 KB) | HTML Full-text | XML Full-text
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New pyrazoline derivatives were synthesized and evaluated for their cytotoxic effects on AsPC-1 human pancreatic adenocarcinoma, U87 and U251 human glioblastoma cell lines. 1-[((5-(4-Methylphenyl)-1,3,4-oxadiazol-2-yl)thio)acetyl]-3-(2-thienyl)-5-(4-chlorophenyl)-2-pyrazoline (11) was found to be the most effective anticancer agent against AsPC-1 and U251 cell lines, with [...] Read more.
New pyrazoline derivatives were synthesized and evaluated for their cytotoxic effects on AsPC-1 human pancreatic adenocarcinoma, U87 and U251 human glioblastoma cell lines. 1-[((5-(4-Methylphenyl)-1,3,4-oxadiazol-2-yl)thio)acetyl]-3-(2-thienyl)-5-(4-chlorophenyl)-2-pyrazoline (11) was found to be the most effective anticancer agent against AsPC-1 and U251 cell lines, with IC50 values of 16.8 µM and 11.9 µM, respectively. Tumor selectivity of compound 11 was clearly seen between Jurkat human leukemic T-cell line and human peripheral blood mononuclear cells (PBMC). Due to its promising anticancer activity, compound 11 was chosen for apoptosis/necrosis evaluation and DNA-cleavage analysis in U251 cells. Compound 11-treated U251 cells exhibited apoptotic phenotype at low concentration (1.5 µM). DNA-cleaving efficiency of this ligand was more significant than cisplatin and was clearly enhanced by Fe(II)-H2O2-ascorbic acid systems. This result pointed out the relationship between the DNA cleavage and the cell death. Full article
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Open AccessArticle Lupanine Improves Glucose Homeostasis by Influencing KATP Channels and Insulin Gene Expression
Molecules 2015, 20(10), 19085-19100; https://doi.org/10.3390/molecules201019085
Received: 8 July 2015 / Revised: 22 September 2015 / Accepted: 13 October 2015 / Published: 20 October 2015
Cited by 8 | Viewed by 2366 | PDF Full-text (1302 KB) | HTML Full-text | XML Full-text
Abstract
The glucose-lowering effects of lupin seeds involve the combined action of several components. The present study investigates the influence of one of the main quinolizidine alkaloids, lupanine, on pancreatic beta cells and in an animal model of type-2 diabetes mellitus. In vitro studies [...] Read more.
The glucose-lowering effects of lupin seeds involve the combined action of several components. The present study investigates the influence of one of the main quinolizidine alkaloids, lupanine, on pancreatic beta cells and in an animal model of type-2 diabetes mellitus. In vitro studies were performed with insulin-secreting INS-1E cells or islets of C57BL/6 mice. In the in vivo experiments, hyperglycemia was induced in rats by injecting streptozotocin (65 mg/kg body weight). In the presence of 15 mmol/L glucose, insulin secretion was significantly elevated by 0.5 mmol/L lupanine, whereas the alkaloid did not stimulate insulin release with lower glucose concentrations. In islets treated with l-arginine, the potentiating effect of lupanine already occurred at 8 mmol/L glucose. Lupanine increased the expression of the Ins-1 gene. The potentiating effect on secretion was correlated to membrane depolarization and an increase in the frequency of Ca2+ action potentials. Determination of the current through ATP-dependent K+ channels (KATP channels) revealed that lupanine directly inhibited the channel. The effect was dose-dependent but, even with a high lupanine concentration of 1 mmol/L or after a prolonged exposure time (12 h), the KATP channel block was incomplete. Oral administration of lupanine did not induce hypoglycemia. By contrast, lupanine improved glycemic control in response to an oral glucose tolerance test in streptozotocin-diabetic rats. In summary, lupanine acts as a positive modulator of insulin release obviously without a risk for hypoglycemic episodes. Full article
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Open AccessArticle Synthesis, Molecular Structure, Metabolic Stability and QSAR Studies of a Novel Series of Anticancer N-Acylbenzenesulfonamides
Molecules 2015, 20(10), 19101-19129; https://doi.org/10.3390/molecules201019101
Received: 9 September 2015 / Revised: 1 October 2015 / Accepted: 12 October 2015 / Published: 21 October 2015
Cited by 7 | Viewed by 1844 | PDF Full-text (1304 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A series of novel N-acyl-4-chloro-5-methyl-2-(R1-methylthio)benzenesulfonamides 1847 have been synthesized by the reaction of N-[4-chloro-5-methyl-2-(R1-methylthio) benzenesulfonyl]cyanamide potassium salts with appropriate carboxylic acids. Some of them showed anticancer activity toward the human cancer cell lines MCF-7, HCT-116 [...] Read more.
A series of novel N-acyl-4-chloro-5-methyl-2-(R1-methylthio)benzenesulfonamides 1847 have been synthesized by the reaction of N-[4-chloro-5-methyl-2-(R1-methylthio) benzenesulfonyl]cyanamide potassium salts with appropriate carboxylic acids. Some of them showed anticancer activity toward the human cancer cell lines MCF-7, HCT-116 and HeLa, with the growth percentages (GPs) in the range from 7% to 46%. Quantitative structure-activity relationship (QSAR) studies on the cytotoxic activity of N-acylsulfonamides toward MCF-7, HCT-116 and HeLa were performed by using topological, ring and charge descriptors based on the stepwise multiple linear regression technique (MLR). The QSAR studies revealed three predictive and statistically significant models for the investigated compounds. The results obtained with these models indicated that the anticancer activity of N-acylsulfonamides depends on topological distances, number of ring system, maximum positive charge and number of atom-centered fragments. The metabolic stability of the selected compounds had been evaluated on pooled human liver microsomes and NADPH, both R1 and R2 substituents of the N-acylsulfonamides simultaneously affected them. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Olefin Metathesis Reaction in Water and in Air Improved by Supramolecular Additives
Molecules 2015, 20(10), 19130-19141; https://doi.org/10.3390/molecules201019130
Received: 23 September 2015 / Revised: 13 October 2015 / Accepted: 14 October 2015 / Published: 21 October 2015
Cited by 9 | Viewed by 2151 | PDF Full-text (1640 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A range of water-immiscible commercially available Grubbs-type precatalysts can be used in ring-closing olefin metathesis reaction in high yields. The synthetic transformation is possible in pure water under ambient conditions. Sulfocalixarenes can help to boost the reactivity of the metathesis reaction by [...] Read more.
A range of water-immiscible commercially available Grubbs-type precatalysts can be used in ring-closing olefin metathesis reaction in high yields. The synthetic transformation is possible in pure water under ambient conditions. Sulfocalixarenes can help to boost the reactivity of the metathesis reaction by catalyst activation, improved mass transfer, and solubility of reactants in the aqueous reaction media. Additionally, the use of supramolecular additives allows lower catalyst loadings, but still high activity in pure water under aerobic conditions. Full article
(This article belongs to the Special Issue Olefin Metathesis)
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Open AccessArticle Iridoids and Flavonoids of Four Siberian Gentians: Chemical Profile and Gastric Stimulatory Effect
Molecules 2015, 20(10), 19172-19188; https://doi.org/10.3390/molecules201019172
Received: 28 August 2015 / Revised: 15 October 2015 / Accepted: 16 October 2015 / Published: 21 October 2015
Cited by 11 | Viewed by 2011 | PDF Full-text (1232 KB) | HTML Full-text | XML Full-text
Abstract
Some Gentiana species have been used by the nomadic people of Siberia as bitter teas or appetizers to eliminate digestive disorders (dyspepsia, heartburn, nausea, etc.). We studied the most frequently used gentians: Gentiana algida, G. decumbens, G. macrophylla and G. triflora [...] Read more.
Some Gentiana species have been used by the nomadic people of Siberia as bitter teas or appetizers to eliminate digestive disorders (dyspepsia, heartburn, nausea, etc.). We studied the most frequently used gentians: Gentiana algida, G. decumbens, G. macrophylla and G. triflora. The aim of the present study was to evaluate the phytochemical features and gastrostimulatnt activity of these four gentian herbs. Five iridoids, seven flavones and mangiferin were detected in gentian herbs after analysis by microcolumn-RP-HPLC-UV-ESI-MS. A componential phytochemical profile of the G. decumbens herb is presented for the first time, as well as information about distinct phytochemicals found in gentian herbs. HPLC quantification of the specific compounds of gentian herbs demonstrated the high content of iridoids (24.73–73.53 mg/g) and flavonoids (12.92–78.14 mg/g). The results of biological activity evaluation of four gentian decoctions demonstrated their good ability to stimulate acid-, enzyme- and mucin-forming functions of the stomach attributed to mostly by iridoids and flavonoids. In general, it can be claimed that the gentian decoctions can be used as effective and safe appetizers and are also a good source of biologically active agents. Full article
(This article belongs to the collection Herbal Medicine Research)
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Open AccessArticle Enhanced Visible Light Photocatalytic Activity of Br-Doped Bismuth Oxide Formate Nanosheets
Molecules 2015, 20(10), 19189-19202; https://doi.org/10.3390/molecules201019189
Received: 7 August 2015 / Revised: 3 October 2015 / Accepted: 14 October 2015 / Published: 21 October 2015
Cited by 5 | Viewed by 2220 | PDF Full-text (5398 KB) | HTML Full-text | XML Full-text
Abstract
A facile method was developed to enhance the visible light photocatalytic activity of bismuth oxide formate (BiOCOOH) nanosheets via Br-doping. The as-prepared samples were characterized by X-ray diffraction, scanning electron microscopy, transmission electron microscopy, X-ray photoelectron spectroscopy, the Brunauer–Emmett–Teller surface area, UV-vis diffuse [...] Read more.
A facile method was developed to enhance the visible light photocatalytic activity of bismuth oxide formate (BiOCOOH) nanosheets via Br-doping. The as-prepared samples were characterized by X-ray diffraction, scanning electron microscopy, transmission electron microscopy, X-ray photoelectron spectroscopy, the Brunauer–Emmett–Teller surface area, UV-vis diffuse reflectance spectroscopy, photoluminescence spectra, and N2 adsorption-desorption isotherms measurement. The Br ions replaced the COOH ions in the layers of BiOCOOH, result in a decreased layer distance. The photocatalytic activity of the as-prepared materials was evaluated by removal of NO in qir at ppb level. The results showed that the Br-doped BiOCOOH nanosheets showed enhanced visible light photocatalytic activtiy with a NO removal of 37.8%. The enhanced activity can be ascribed to the increased visible light absorption and the promoted charge separation. Full article
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Open AccessArticle Greener Selective Cycloalkane Oxidations with Hydrogen Peroxide Catalyzed by Copper-5-(4-pyridyl)tetrazolate Metal-Organic Frameworks
Molecules 2015, 20(10), 19203-19220; https://doi.org/10.3390/molecules201019203
Received: 25 September 2015 / Revised: 13 October 2015 / Accepted: 16 October 2015 / Published: 21 October 2015
Cited by 9 | Viewed by 2220 | PDF Full-text (1083 KB) | HTML Full-text | XML Full-text
Abstract
Microwave assisted synthesis of the Cu(I) compound [Cu(µ4-4-ptz)]n [1, 4-ptz = 5-(4-pyridyl)tetrazolate]has been performed by employing a relatively easy method and within a shorter period of time compared to its sister compounds. The syntheses of the Cu(II) [...] Read more.
Microwave assisted synthesis of the Cu(I) compound [Cu(µ4-4-ptz)]n [1, 4-ptz = 5-(4-pyridyl)tetrazolate] has been performed by employing a relatively easy method and within a shorter period of time compared to its sister compounds. The syntheses of the Cu(II) compounds [Cu33-4-ptz)42-N3)2(DMF)2]n∙(DMF)2n (2) and [Cu(µ2-4-ptz)2(H2O)2]n (3) using a similar method were reported previously by us. MOFs 1-3 revealed high catalytic activity toward oxidation of cyclic alkanes (cyclopentane, -hexane and -octane) with aqueous hydrogen peroxide, under very mild conditions (at room temperature), without any added solvent or additive. The most efficient system (2/H2O2) showed, for the oxidation of cyclohexane, a turnover number (TON) of 396 (TOF of 40 h−1), with an overall product yield (cyclohexanol and cyclohexanone) of 40% relative to the substrate. Moreover, the heterogeneous catalytic systems 13 allowed an easy catalyst recovery and reuse, at least for four consecutive cycles, maintaining ca. 90% of the initial high activity and concomitant high selectivity. Full article
(This article belongs to the Special Issue Metal Mediated Activation of Small Molecules)
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Open AccessArticle γ-Alumina Nanoparticle Catalyzed Efficient Synthesis of Highly Substituted Imidazoles
Molecules 2015, 20(10), 19221-19235; https://doi.org/10.3390/molecules201019221
Received: 6 September 2015 / Revised: 11 October 2015 / Accepted: 14 October 2015 / Published: 21 October 2015
Cited by 5 | Viewed by 1603 | PDF Full-text (2518 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
γ-Alumina nano particle catalyzed multi component reaction of benzil, arylaldehyde and aryl amines afforded the highly substituted 1,2,4,5-tetraaryl imidazoles with good to excellent yield in less reaction time under the sonication as well as the conventional methods. Convenient operational simplicity, mild conditions and [...] Read more.
γ-Alumina nano particle catalyzed multi component reaction of benzil, arylaldehyde and aryl amines afforded the highly substituted 1,2,4,5-tetraaryl imidazoles with good to excellent yield in less reaction time under the sonication as well as the conventional methods. Convenient operational simplicity, mild conditions and the reusability of catalyst were the other advantages of this developed protocol. Full article
(This article belongs to the Section Organic Chemistry)
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Open AccessArticle A Self-Adaptive Steered Molecular Dynamics Method Based on Minimization of Stretching Force Reveals the Binding Affinity of Protein–Ligand Complexes
Molecules 2015, 20(10), 19236-19251; https://doi.org/10.3390/molecules201019236
Received: 31 August 2015 / Revised: 14 October 2015 / Accepted: 14 October 2015 / Published: 22 October 2015
Cited by 9 | Viewed by 1818 | PDF Full-text (1790 KB) | HTML Full-text | XML Full-text
Abstract
Binding affinity prediction of protein–ligand complexes has attracted widespread interest. In this study, a self-adaptive steered molecular dynamics (SMD) method is proposed to reveal the binding affinity of protein–ligand complexes. The SMD method is executed through adjusting pulling direction to find an optimum [...] Read more.
Binding affinity prediction of protein–ligand complexes has attracted widespread interest. In this study, a self-adaptive steered molecular dynamics (SMD) method is proposed to reveal the binding affinity of protein–ligand complexes. The SMD method is executed through adjusting pulling direction to find an optimum trajectory of ligand dissociation, which is realized by minimizing the stretching force automatically. The SMD method is then used to simulate the dissociations of 19 common protein–ligand complexes which are derived from two homology families, and the binding free energy values are gained through experimental techniques. Results show that the proposed SMD method follows a different dissociation pathway with lower a rupture force and energy barrier when compared with the conventional SMD method, and further analysis indicates the rupture forces of the complexes in the same protein family correlate well with their binding free energy, which reveals the possibility of using the proposed SMD method to identify the active ligand. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Cytotoxicity of Triterpenes from Green Walnut Husks of Juglans mandshurica Maxim in HepG-2 Cancer Cells
Molecules 2015, 20(10), 19252-19262; https://doi.org/10.3390/molecules201019252
Received: 6 September 2015 / Revised: 15 October 2015 / Accepted: 19 October 2015 / Published: 22 October 2015
Cited by 10 | Viewed by 2213 | PDF Full-text (837 KB) | HTML Full-text | XML Full-text
Abstract
Among the classes of identified natural products, triterpenoids, one of the largest families, have been studied extensively for their diverse structures and variety of biological activities, including antitumor effects. In the present study, a phytochemical study of the green walnut husks of Juglans [...] Read more.
Among the classes of identified natural products, triterpenoids, one of the largest families, have been studied extensively for their diverse structures and variety of biological activities, including antitumor effects. In the present study, a phytochemical study of the green walnut husks of Juglans mandshurica Maxim led to the isolation of a new dammarane triterpene, 12β, 20(R), 24(R)-trihydroxydammar-25-en-3-one (6), together with sixteen known compounds, chiefly from chloroform and ethyl acetate extracts. According to their structural characteristics, these compounds were divided into dammarane-type, oleanane- and ursane-type. Dammarane-type triterpenoids were isolated for the first time from the Juglans genus. As part of our continuing search for biologically active compounds from this plant, all of these compounds were also evaluated for their cytotoxic activities against the growth of human cancer cells lines HepG-2 by the MTT assay. The results were shown that 20(S)-protopanaxadiol, 2α,3β,23-trihydroxyolean-12-en-28-oic acid and 2α,3β,23-trihydroxyurs-12-en-28-oic acid exhibited better cytotoxicity in vitro with IC50 values of 10.32 ± 1.13, 16.13 ± 3.83, 15.97 ± 2.47 μM, respectively. Preliminary structure-activity relationships for these compounds were discussed. Full article
(This article belongs to the collection Bioactive Compounds)
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Open AccessArticle Novel 2-Thioxanthine and Dipyrimidopyridine Derivatives: Synthesis and Antimicrobial Activity
Molecules 2015, 20(10), 19263-19276; https://doi.org/10.3390/molecules201019263
Received: 22 August 2015 / Revised: 3 October 2015 / Accepted: 12 October 2015 / Published: 22 October 2015
Cited by 4 | Viewed by 1910 | PDF Full-text (310 KB) | HTML Full-text | XML Full-text | Correction
Abstract
Several fused imidazolopyrimidines were synthesized starting from 6-amino-1-methyl-2-thiouracil (1) followed by nitrosation, reduction and condensation with different aromatic aldehydes to give Schiff’s base. The dehydrocyclization of Schiff’s bases using iodine/DMF gave Compounds 5ag. The methylation of 5a [...] Read more.
Several fused imidazolopyrimidines were synthesized starting from 6-amino-1-methyl-2-thiouracil (1) followed by nitrosation, reduction and condensation with different aromatic aldehydes to give Schiff’s base. The dehydrocyclization of Schiff’s bases using iodine/DMF gave Compounds 5ag. The methylation of 5ag using a simple alkylating agent as dimethyl sulfate ((CH3)2SO4) gave either monoalkylated imidazolopyrimidine 6ag at room temperature or dialkylated derivatives 7ag on heating 6ag with ((CH3)2SO4). On the other hand, treatment of 1 with different aromatic aldehydes in absolute ethanol in the presence of conc. hydrochloric acid at room temperature and/or reflux with acetic acid afforded bis-5,5́-diuracylmethylene 8ae, which cyclized on heating with a mixture of acetic acid/HCl (1:1) to give 9ae. Compounds 9ae can be obtained directly by refluxing of Compound 1 with a mixture of acetic acid/HCl. The synthesized new compounds were screened for antimicrobial activity, and the MIC was measured. Full article
(This article belongs to the collection Heterocyclic Compounds)
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Open AccessArticle Antimycobacterial Activities of Endolysins Derived From a Mycobacteriophage, BTCU-1
Molecules 2015, 20(10), 19277-19290; https://doi.org/10.3390/molecules201019277
Received: 25 September 2015 / Revised: 15 October 2015 / Accepted: 16 October 2015 / Published: 22 October 2015
Cited by 9 | Viewed by 2063 | PDF Full-text (3300 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The high incidence of Mycobacterium infection, notably multidrug-resistant M. tuberculosis infection, has become a significant public health concern worldwide. In this study, we isolate and analyze a mycobacteriophage, BTCU-1, and a foundational study was performed to evaluate the antimycobacterial activity of BTCU-1 and [...] Read more.
The high incidence of Mycobacterium infection, notably multidrug-resistant M. tuberculosis infection, has become a significant public health concern worldwide. In this study, we isolate and analyze a mycobacteriophage, BTCU-1, and a foundational study was performed to evaluate the antimycobacterial activity of BTCU-1 and its cloned lytic endolysins. Using Mycobacterium smegmatis as host, a mycobacteriophage, BTCU-1, was isolated from soil in eastern Taiwan. The electron microscopy images revealed that BTCU-1 displayed morphology resembling the Siphoviridae family. In the genome of BTCU-1, two putative lytic genes, BTCU-1_ORF7 and BTCU-1_ORF8 (termed lysA and lysB, respectively), were identified, and further subcloned and expressed in Escherichia coli. When applied exogenously, both LysA and LysB were active against M. smegmatis tested. Scanning electron microscopy revealed that LysA and LysB caused a remarkable modification of the cell shape of M. smegmatis. Intracellular bactericidal activity assay showed that treatment of M. smegmatis—infected RAW 264.7 macrophages with LysA or LysB resulted in a significant reduction in the number of viable intracellular bacilli. These results indicate that the endolysins derived from BTCU-1 have antimycobacterial activity, and suggest that they are good candidates for therapeutic/disinfectant agents to control mycobacterial infections. Full article
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Open AccessArticle Highly Selective Bioconversion of Ginsenoside Rb1 to Compound K by the Mycelium of Cordyceps sinensis under Optimized Conditions
Molecules 2015, 20(10), 19291-19309; https://doi.org/10.3390/molecules201019291
Received: 10 August 2015 / Revised: 1 October 2015 / Accepted: 2 October 2015 / Published: 23 October 2015
Cited by 7 | Viewed by 2575 | PDF Full-text (3055 KB) | HTML Full-text | XML Full-text
Abstract
Compound K (CK), a highly active and bioavailable derivative obtained from protopanaxadiol ginsenosides, displays a wide variety of pharmacological properties, especially antitumor activity. However, the inadequacy of natural sources limits its application in the pharmaceutical industry. In this study, we firstly discovered that [...] Read more.
Compound K (CK), a highly active and bioavailable derivative obtained from protopanaxadiol ginsenosides, displays a wide variety of pharmacological properties, especially antitumor activity. However, the inadequacy of natural sources limits its application in the pharmaceutical industry. In this study, we firstly discovered that Cordyceps sinensis was a potent biocatalyst for the biotransformation of ginsenoside Rb1 into CK. After a series of investigations on the biotransformation parameters, an optimal composition of the biotransformation culture was found to be lactose, soybean powder and MgSO4 without controlling the pH. Also, an optimum temperature of 30 °C for the biotransformation process was suggested in a range of 25 °C–50 °C. Then, a biotransformation pathway of Rb1 → Rd → F2 → CK was established using high performance liquid chromatography/quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF-MS). Our results demonstrated that the molar bioconversion rate of Rb1 to CK was more than 82% and the purity of CK produced by C. sinensis under the optimized conditions was more than 91%. In conclusion, the combination of C. sinensis and the optimized conditions is applicable for the industrial preparation of CK for medicinal purposes. Full article
(This article belongs to the Section Natural Products Chemistry)
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