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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; doi:10.3390/molecules201017720
Received: 21 August 2015 / Revised: 18 September 2015 / Accepted: 22 September 2015 / Published: 25 September 2015
Cited by 3 | 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)
Open AccessCommunication Identification of Minor Benzoylated 4-Phenylcoumarins from a Mammea neurophylla Bark Extract
Molecules 2015, 20(10), 17735-17746; doi:10.3390/molecules201017735
Received: 7 July 2015 / Revised: 25 August 2015 / Accepted: 17 September 2015 / Published: 25 September 2015
Cited by 2 | 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
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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; doi:10.3390/molecules201017747
Received: 10 August 2015 / Revised: 18 September 2015 / Accepted: 21 September 2015 / Published: 25 September 2015
Cited by 2 | 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
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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)
Open AccessArticle Enhanced Bioaccessibility of Crocetin Sugar Esters from Saffron in Infusions Rich in Natural Phenolic Antioxidants
Molecules 2015, 20(10), 17760-17774; doi:10.3390/molecules201017760
Received: 25 August 2015 / Revised: 15 September 2015 / Accepted: 21 September 2015 / Published: 25 September 2015
Cited by 2 | 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.
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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; doi:10.3390/molecules201017775
Received: 10 June 2015 / Revised: 11 September 2015 / Accepted: 18 September 2015 / Published: 25 September 2015
Cited by 6 | 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
Open AccessArticle Is Promiscuous CALB a Good Scaffold for Designing New Epoxidases?
Molecules 2015, 20(10), 17789-17806; doi:10.3390/molecules201017789
Received: 7 August 2015 / Revised: 10 September 2015 / Accepted: 11 September 2015 / Published: 25 September 2015
Cited by 3 | 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
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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; doi:10.3390/molecules201017807
Received: 15 July 2015 / Revised: 10 September 2015 / Accepted: 17 September 2015 / Published: 25 September 2015
Cited by 6 | 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; doi:10.3390/molecules201017848
Received: 27 August 2015 / Revised: 15 September 2015 / Accepted: 22 September 2015 / Published: 25 September 2015
Cited by 13 | 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)
Open AccessArticle Amination of Aryl Halides and Esters Using Intensified Continuous Flow Processing
Molecules 2015, 20(10), 17860-17871; doi:10.3390/molecules201017860
Received: 25 August 2015 / Revised: 17 September 2015 / Accepted: 22 September 2015 / Published: 25 September 2015
Cited by 1 | 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
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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; doi:10.3390/molecules201017872
Received: 28 July 2015 / Revised: 21 September 2015 / Accepted: 23 September 2015 / Published: 29 September 2015
Cited by 7 | 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; doi:10.3390/molecules201017883
Received: 16 July 2015 / Revised: 21 September 2015 / Accepted: 21 September 2015 / Published: 29 September 2015
Cited by 5 | 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
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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)
Open AccessArticle Activity of Polyphenolic Compounds against Candida glabrata
Molecules 2015, 20(10), 17903-17912; doi:10.3390/molecules201017903
Received: 15 July 2015 / Revised: 16 September 2015 / Accepted: 24 September 2015 / Published: 29 September 2015
Cited by 4 | 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; doi:10.3390/molecules201017913
Received: 1 August 2015 / Revised: 7 September 2015 / Accepted: 22 September 2015 / Published: 29 September 2015
Cited by 9 | 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
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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)
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; doi:10.3390/molecules201017929
Received: 6 July 2015 / Revised: 31 August 2015 / Accepted: 10 September 2015 / Published: 30 September 2015
Cited by 7 | 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
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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)
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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; doi:10.3390/molecules201017976
Received: 28 February 2015 / Revised: 20 September 2015 / Accepted: 21 September 2015 / Published: 30 September 2015
Cited by 13 | 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)
Open AccessArticle Cucurbitacins from the Leaves of Citrullus colocynthis (L.) Schrad
Molecules 2015, 20(10), 18001-18015; doi:10.3390/molecules201018001
Received: 8 July 2015 / Revised: 14 September 2015 / Accepted: 23 September 2015 / Published: 30 September 2015
Cited by 3 | 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)
Open AccessArticle Treatment Efficiency of Free and Nanoparticle-Loaded Mitoxantrone for Magnetic Drug Targeting in Multicellular Tumor Spheroids
Molecules 2015, 20(10), 18016-18030; doi:10.3390/molecules201018016
Received: 14 August 2015 / Revised: 14 September 2015 / Accepted: 24 September 2015 / Published: 30 September 2015
Cited by 4 | 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
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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)
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; doi:10.3390/molecules201018031
Received: 26 August 2015 / Revised: 24 September 2015 / Accepted: 27 September 2015 / Published: 30 September 2015
Cited by 4 | 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
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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; doi:10.3390/molecules201018047
Received: 14 August 2015 / Revised: 22 September 2015 / Accepted: 24 September 2015 / Published: 1 October 2015
Cited by 4 | 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
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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)
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; doi:10.3390/molecules201018066
Received: 4 September 2015 / Revised: 21 September 2015 / Accepted: 29 September 2015 / Published: 2 October 2015
Cited by 2 | 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.
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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; doi:10.3390/molecules201018083
Received: 13 August 2015 / Revised: 16 September 2015 / Accepted: 17 September 2015 / Published: 2 October 2015
Cited by 4 | 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
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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; doi:10.3390/molecules201018095
Received: 7 August 2015 / Revised: 24 September 2015 / Accepted: 30 September 2015 / Published: 2 October 2015
Cited by 3 | 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
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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)
Open AccessArticle A Quantum-Based Similarity Method in Virtual Screening
Molecules 2015, 20(10), 18107-18127; doi:10.3390/molecules201018107
Received: 26 August 2015 / Revised: 22 September 2015 / Accepted: 23 September 2015 / Published: 2 October 2015
Cited by 5 | 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
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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)
Open AccessArticle Phytochemical and Biological Investigation of Two Diplotaxis Species Growing in Tunisia: D. virgata & D. erucoides
Molecules 2015, 20(10), 18128-18143; doi:10.3390/molecules201018128
Received: 24 July 2015 / Revised: 11 August 2015 / Accepted: 13 August 2015 / Published: 5 October 2015
Cited by 3 | 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
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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)
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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; doi:10.3390/molecules201018144
Received: 16 July 2015 / Revised: 28 September 2015 / Accepted: 29 September 2015 / Published: 6 October 2015
Cited by 16 | 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
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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; doi:10.3390/molecules201018185
Received: 17 August 2015 / Revised: 5 September 2015 / Accepted: 15 September 2015 / Published: 7 October 2015
Cited by 6 | 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
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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; doi:10.3390/molecules201018201
Received: 5 September 2015 / Revised: 20 September 2015 / Accepted: 23 September 2015 / Published: 7 October 2015
Cited by 7 | 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
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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)
Open AccessArticle Potential of Essential Oils as Penetration Enhancers for Transdermal Administration of Ibuprofen to Treat Dysmenorrhoea
Molecules 2015, 20(10), 18219-18236; doi:10.3390/molecules201018219
Received: 3 September 2015 / Revised: 27 September 2015 / Accepted: 28 September 2015 / Published: 7 October 2015
Cited by 11 | 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
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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; doi:10.3390/molecules201018237
Received: 30 July 2015 / Revised: 16 September 2015 / Accepted: 21 September 2015 / Published: 7 October 2015
Cited by 2 | 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
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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; doi:10.3390/molecules201018246
Received: 19 June 2015 / Revised: 2 October 2015 / Accepted: 2 October 2015 / Published: 7 October 2015
Cited by 3 | 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 ±
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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; doi:10.3390/molecules201018264
Received: 25 August 2015 / Revised: 30 September 2015 / Accepted: 30 September 2015 / Published: 7 October 2015
Cited by 4 | 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
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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)
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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; doi:10.3390/molecules201018279
Received: 5 August 2015 / Revised: 25 September 2015 / Accepted: 29 September 2015 / Published: 7 October 2015
Cited by 5 | 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,
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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)
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; doi:10.3390/molecules201018352
Received: 5 August 2015 / Revised: 28 September 2015 / Accepted: 1 October 2015 / Published: 8 October 2015
Cited by 7 | 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
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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)
Open AccessArticle Synthesis and Spectroscopic Evaluation of Two Novel Glycosylated Zinc(II)-Phthalocyanines
Molecules 2015, 20(10), 18367-18386; doi:10.3390/molecules201018367
Received: 23 September 2015 / Revised: 5 October 2015 / Accepted: 6 October 2015 / Published: 9 October 2015
Cited by 2 | 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)
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; doi:10.3390/molecules201018387
Received: 15 July 2015 / Revised: 25 September 2015 / Accepted: 28 September 2015 / Published: 9 October 2015
Cited by 4 | 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
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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)
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; doi:10.3390/molecules201018422
Received: 5 August 2015 / Revised: 11 September 2015 / Accepted: 17 September 2015 / Published: 9 October 2015
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
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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)
Open AccessArticle Cladribine Analogues via O6-(Benzotriazolyl) Derivatives of Guanine Nucleosides
Molecules 2015, 20(10), 18437-18463; doi:10.3390/molecules201018437
Received: 17 August 2015 / Revised: 20 September 2015 / Accepted: 22 September 2015 / Published: 9 October 2015
Cited by 3 | 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
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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; doi:10.3390/molecules201018482
Received: 2 September 2015 / Revised: 22 September 2015 / Accepted: 23 September 2015 / Published: 9 October 2015
Cited by 3 | 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
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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; doi:10.3390/molecules201018496
Received: 31 August 2015 / Revised: 25 September 2015 / Accepted: 29 September 2015 / Published: 9 October 2015
Cited by 4 | 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)
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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; doi:10.3390/molecules201018511
Received: 31 August 2015 / Revised: 24 September 2015 / Accepted: 6 October 2015 / Published: 9 October 2015
Cited by 6 | 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
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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; doi:10.3390/molecules201018526
Received: 1 September 2015 / Revised: 30 September 2015 / Accepted: 5 October 2015 / Published: 9 October 2015
Cited by 4 | 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
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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; doi:10.3390/molecules201018539
Received: 25 July 2015 / Revised: 10 September 2015 / Accepted: 25 September 2015 / Published: 12 October 2015
Cited by 2 | 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
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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)
Open AccessArticle Limonoids from the Seeds of Swietenia macrophylla and Their Anti-Inflammatory Activities
Molecules 2015, 20(10), 18551-18564; doi:10.3390/molecules201018551
Received: 23 August 2015 / Revised: 2 October 2015 / Accepted: 5 October 2015 / Published: 12 October 2015
Cited by 4 | 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
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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)
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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; doi:10.3390/molecules201018565
Received: 1 August 2015 / Revised: 3 October 2015 / Accepted: 7 October 2015 / Published: 13 October 2015
Cited by 2 | 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
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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; doi:10.3390/molecules201018585
Received: 19 June 2015 / Revised: 29 September 2015 / Accepted: 30 September 2015 / Published: 13 October 2015
Cited by 4 | 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
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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; doi:10.3390/molecules201018597
Received: 17 July 2015 / Revised: 23 September 2015 / Accepted: 6 October 2015 / Published: 14 October 2015
Cited by 8 | 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
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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)
Open AccessArticle Resin-Immobilized Palladium Nanoparticle Catalysts for Organic Reactions in Aqueous Media: Morphological Aspects
Molecules 2015, 20(10), 18661-18684; doi:10.3390/molecules201018661
Received: 24 September 2015 / Revised: 8 October 2015 / Accepted: 8 October 2015 / Published: 14 October 2015
Cited by 4 | 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)
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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; doi:10.3390/molecules201018685
Received: 5 August 2015 / Revised: 7 September 2015 / Accepted: 18 September 2015 / Published: 14 October 2015
Cited by 5 | 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
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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; doi:10.3390/molecules201018704
Received: 23 August 2015 / Revised: 2 October 2015 / Accepted: 7 October 2015 / Published: 15 October 2015
Cited by 7 | 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
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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)
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; doi:10.3390/molecules201018717
Received: 10 July 2015 / Revised: 22 September 2015 / Accepted: 12 October 2015 / Published: 15 October 2015
Cited by 2 | 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
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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)
Open AccessArticle In Vitro Cytoprotective Effects and Antioxidant Capacity of Phenolic Compounds from the Leaves of Swietenia macrophylla
Molecules 2015, 20(10), 18777-18788; doi:10.3390/molecules201018777
Received: 16 July 2015 / Revised: 18 August 2015 / Accepted: 25 August 2015 / Published: 16 October 2015
Cited by 2 | 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
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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; doi:10.3390/molecules201018789
Received: 1 September 2015 / Revised: 15 September 2015 / Accepted: 17 September 2015 / Published: 16 October 2015
Cited by 3 | 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
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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 Synthesis)
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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; doi:10.3390/molecules201018808
Received: 16 August 2015 / Revised: 15 September 2015 / Accepted: 21 September 2015 / Published: 16 October 2015
Cited by 2 | 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
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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; doi:10.3390/molecules201018827
Received: 24 August 2015 / Revised: 31 August 2015 / Accepted: 5 October 2015 / Published: 16 October 2015
Cited by 3 | 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),
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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)
Open AccessCommunication Amine-Functionalized ZnO Nanosheets for Efficient CO2 Capture and Photoreduction
Molecules 2015, 20(10), 18847-18855; doi:10.3390/molecules201018847
Received: 20 August 2015 / Revised: 7 October 2015 / Accepted: 14 October 2015 / Published: 16 October 2015
Cited by 9 | 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
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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
Open AccessArticle Maleimides Designed for Self-Assembly and Reactivity on Graphene
Molecules 2015, 20(10), 18856-18869; doi:10.3390/molecules201018856
Received: 26 August 2015 / Revised: 12 October 2015 / Accepted: 13 October 2015 / Published: 16 October 2015
PDF Full-text (987 KB) | HTML Full-text | XML Full-text | Supplementary Files
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
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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 Synthesis)
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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; doi:10.3390/molecules201018870
Received: 30 June 2015 / Revised: 3 October 2015 / Accepted: 7 October 2015 / Published: 16 October 2015
Cited by 4 | 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
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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)
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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; doi:10.3390/molecules201018907
Received: 22 July 2015 / Revised: 26 August 2015 / Accepted: 9 October 2015 / Published: 16 October 2015
Cited by 7 | 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
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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
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; doi:10.3390/molecules201018967
Received: 22 August 2015 / Revised: 9 October 2015 / Accepted: 12 October 2015 / Published: 19 October 2015
Cited by 2 | 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
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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; doi:10.3390/molecules201018988
Received: 18 September 2015 / Revised: 12 October 2015 / Accepted: 13 October 2015 / Published: 19 October 2015
Cited by 3 | 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
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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; doi:10.3390/molecules201019002
Received: 1 September 2015 / Revised: 7 October 2015 / Accepted: 13 October 2015 / Published: 19 October 2015
Cited by 2 | 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
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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)
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; doi:10.3390/molecules201019014
Received: 13 August 2015 / Revised: 3 October 2015 / Accepted: 15 October 2015 / Published: 20 October 2015
Cited by 2 | 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
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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)
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Open AccessArticle miRNA Stability in Frozen Plasma Samples
Molecules 2015, 20(10), 19030-19040; doi:10.3390/molecules201019030
Received: 24 July 2015 / Revised: 9 October 2015 / Accepted: 13 October 2015 / Published: 20 October 2015
Cited by 12 | 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
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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)
Open AccessArticle Thermal Influence of CNT on the Polyamide 12 Nanocomposite for Selective Laser Sintering
Molecules 2015, 20(10), 19041-19050; doi:10.3390/molecules201019041
Received: 17 September 2015 / Revised: 2 October 2015 / Accepted: 14 October 2015 / Published: 20 October 2015
Cited by 12 | 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
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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
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; doi:10.3390/molecules201019051
Received: 11 August 2015 / Revised: 11 October 2015 / Accepted: 15 October 2015 / Published: 20 October 2015
Cited by 2 | 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
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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)
Open AccessArticle Synthesis and Evaluation of New Pyrazoline Derivatives as Potential Anticancer Agents
Molecules 2015, 20(10), 19066-19084; doi:10.3390/molecules201019066
Received: 17 August 2015 / Revised: 14 October 2015 / Accepted: 14 October 2015 / Published: 20 October 2015
Cited by 11 | PDF Full-text (540 KB) | HTML Full-text | XML Full-text
Abstract
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; doi:10.3390/molecules201019085
Received: 8 July 2015 / Revised: 22 September 2015 / Accepted: 13 October 2015 / Published: 20 October 2015
Cited by 2 | 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
Open AccessArticle Synthesis, Molecular Structure, Metabolic Stability and QSAR Studies of a Novel Series of Anticancer N-Acylbenzenesulfonamides
Molecules 2015, 20(10), 19101-19129; doi:10.3390/molecules201019101
Received: 9 September 2015 / Revised: 1 October 2015 / Accepted: 12 October 2015 / Published: 21 October 2015
Cited by 2 | 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
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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; doi:10.3390/molecules201019130
Received: 23 September 2015 / Revised: 13 October 2015 / Accepted: 14 October 2015 / Published: 21 October 2015
Cited by 5 | 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
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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; doi:10.3390/molecules201019172
Received: 28 August 2015 / Revised: 15 October 2015 / Accepted: 16 October 2015 / Published: 21 October 2015
Cited by 6 | 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
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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; doi:10.3390/molecules201019189
Received: 7 August 2015 / Revised: 3 October 2015 / Accepted: 14 October 2015 / Published: 21 October 2015
Cited by 1 | 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
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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
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; doi:10.3390/molecules201019203
Received: 25 September 2015 / Revised: 13 October 2015 / Accepted: 16 October 2015 / Published: 21 October 2015
Cited by 5 | 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)
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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; doi:10.3390/molecules201019221
Received: 6 September 2015 / Revised: 11 October 2015 / Accepted: 14 October 2015 / Published: 21 October 2015
Cited by 2 | 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
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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 Synthesis)
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; doi:10.3390/molecules201019236
Received: 31 August 2015 / Revised: 14 October 2015 / Accepted: 14 October 2015 / Published: 22 October 2015
Cited by 5 | 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
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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)
Open AccessArticle Cytotoxicity of Triterpenes from Green Walnut Husks of Juglans mandshurica Maxim in HepG-2 Cancer Cells
Molecules 2015, 20(10), 19252-19262; doi:10.3390/molecules201019252
Received: 6 September 2015 / Revised: 15 October 2015 / Accepted: 19 October 2015 / Published: 22 October 2015
Cited by 5 | 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
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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; doi:10.3390/molecules201019263
Received: 22 August 2015 / Revised: 3 October 2015 / Accepted: 12 October 2015 / Published: 22 October 2015
Cited by 2 | PDF Full-text (728 KB) | HTML Full-text | XML Full-text
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
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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; doi:10.3390/molecules201019277
Received: 25 September 2015 / Revised: 15 October 2015 / Accepted: 16 October 2015 / Published: 22 October 2015
Cited by 4 | 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
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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
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; doi:10.3390/molecules201019291
Received: 10 August 2015 / Revised: 1 October 2015 / Accepted: 2 October 2015 / Published: 23 October 2015
Cited by 5 | 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
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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)
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Open AccessArticle A CuAAC–Hydrazone–CuAAC Trifunctional Scaffold for the Solid-Phase Synthesis of Trimodal Compounds: Possibilities and Limitations
Molecules 2015, 20(10), 19310-19329; doi:10.3390/molecules201019310
Received: 28 August 2015 / Revised: 14 October 2015 / Accepted: 16 October 2015 / Published: 23 October 2015
Cited by 2 | PDF Full-text (811 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
We present a trifunctional scaffold designed for the solid-phase synthesis of trimodal compounds. This scaffold holds two alkyne arms in a free and TIPS-protected form for consecutive CuAAC (copper(I)-catalyzed azide–alkyne cycloaddition), one Fmoc-protected hydrazide arm for reaction with aldehydes, and one carboxylic acid
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We present a trifunctional scaffold designed for the solid-phase synthesis of trimodal compounds. This scaffold holds two alkyne arms in a free and TIPS-protected form for consecutive CuAAC (copper(I)-catalyzed azide–alkyne cycloaddition), one Fmoc-protected hydrazide arm for reaction with aldehydes, and one carboxylic acid arm with CF2 groups for attachment to the resin and 19F-NMR quantification. This scaffold was attached to a resin and derivatized with model azides and aliphatic, electron-rich or electron-poor aromatic aldehydes. We identified several limitations of the scaffold caused by the instability of hydrazones in acidic conditions, in the presence of copper during CuAAC, and when copper accumulated in the resin. We successfully overcame these drawbacks by optimizing synthetic conditions for the derivatization of the scaffold with aromatic aldehydes. Overall, the new trifunctional scaffold combines CuAAC and hydrazone chemistries, offering a broader chemical space for the development of bioactive compounds. Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessArticle Poly(Propylene Imine) Dendrimers and Amoxicillin as Dual-Action Antibacterial Agents
Molecules 2015, 20(10), 19330-19342; doi:10.3390/molecules201019330
Received: 25 September 2015 / Revised: 14 October 2015 / Accepted: 16 October 2015 / Published: 23 October 2015
Cited by 5 | PDF Full-text (1275 KB) | HTML Full-text | XML Full-text
Abstract
Besides acting as antimicrobial compounds, dendrimers can be considered as agents that improve the therapeutic effectiveness of existing antibiotics. In this work we present a new approach to using amoxicillin (AMX) against reference strains of common Gram-negative pathogens, alone and in combination with
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Besides acting as antimicrobial compounds, dendrimers can be considered as agents that improve the therapeutic effectiveness of existing antibiotics. In this work we present a new approach to using amoxicillin (AMX) against reference strains of common Gram-negative pathogens, alone and in combination with poly(propylene imine) (PPI) dendrimers, or derivatives thereof, in which 100% of the available hydrogen atoms are substituted with maltose (PPI 100%malG3). The concentrations of dendrimers used remained in the range non-toxic to eukaryotic cells. The results indicate that PPI dendrimers significantly enhance the antibacterial effect of amoxicillin alone, allowing antibiotic doses to be reduced. It is important to reduce doses of amoxicillin because its widespread use in medicine could lead to the development of bacterial resistance and environmental pollution. This is the first report on the combined antibacterial activity of PPI surface-modified maltose dendrimers and amoxicillin. Full article
(This article belongs to the collection Nanomedicine)
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Open AccessArticle Analysis of the Photophysical Behavior and Rotational-Relaxation Dynamics of Coumarin 6 in Nonionic Micellar Environments: The Effect of Temperature
Molecules 2015, 20(10), 19343-19360; doi:10.3390/molecules201019343
Received: 10 September 2015 / Revised: 8 October 2015 / Accepted: 16 October 2015 / Published: 23 October 2015
Cited by 4 | PDF Full-text (1234 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The photodynamics of Coumarin 6 have been investigated in three nonionic micellar assemblies, i.e., n-dodecyl-β-d-maltoside (β-C12G2), p-tert-octyl-phenoxy polyethylene (9.5) ether (Triton X-100 or TX100) and n-dodecyl-hexaethylene-glycol (C12E6), to assess their potential
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The photodynamics of Coumarin 6 have been investigated in three nonionic micellar assemblies, i.e., n-dodecyl-β-d-maltoside (β-C12G2), p-tert-octyl-phenoxy polyethylene (9.5) ether (Triton X-100 or TX100) and n-dodecyl-hexaethylene-glycol (C12E6), to assess their potential use as encapsulation vehicles for hydrophobic drugs. To evaluate the effect of the micellar size and hydration, the study used a broad temperature range (293.15–323.15 K). The data presented here include steady-state absorption and emission spectra of the probe, dynamic light scattering, together with fluorescence lifetimes and both steady-state, as well as time-resolved fluorescence anisotropies. The time-resolved fluorescence anisotropy data were analyzed on the basis of the well-established two-step model. Our data reveal that the molecular probe in all of the cases is solubilized in the hydration layer of micelles, where it would sense a relatively polar environment. However, the probe was found to undergo a slower rotational reorientation when solubilized in the alkylpolyglycoside surfactant, as a result of a more compact microenvironment around the probe. The behavior of the parameters of the reorientation dynamics with temperature was analyzed on the basis of both micellar hydration and the head-group flexibility of the surfactants. Full article
(This article belongs to the Special Issue Coumarins, Xanthones and Related Compounds)
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Open AccessArticle Design, Synthesis, Activity and Docking Study of Sorafenib Analogs Bearing Sulfonylurea Unit
Molecules 2015, 20(10), 19361-19371; doi:10.3390/molecules201019361
Received: 10 August 2015 / Revised: 21 September 2015 / Accepted: 21 September 2015 / Published: 23 October 2015
Cited by 11 | PDF Full-text (296 KB) | HTML Full-text | XML Full-text
Abstract
Two series of novel sorafenib analogs containing a sulfonylurea unit were synthesized and their chemical structures were confirmed by 1H-NMR, 13C-NMR, MS spectrum and elemental analysis. The synthesized compounds were evaluated for the cytotoxicity against A549, Hela, MCF-7, and PC-3
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Two series of novel sorafenib analogs containing a sulfonylurea unit were synthesized and their chemical structures were confirmed by 1H-NMR, 13C-NMR, MS spectrum and elemental analysis. The synthesized compounds were evaluated for the cytotoxicity against A549, Hela, MCF-7, and PC-3 cancer cell lines. Some of the compounds showed moderate cytotoxic activity, especially compounds 1-(2,4-difluorophenylsulfonyl)-3-(4-(2-(methylcarbamoyl)pyridin-4-yloxy)phenyl)urea (6c) and 1-(4-bromophenylsulfonyl)-3-(4-(2-(methylcarbamoyl)pyridin-4-yloxy)phenyl)urea (6f) with the IC50 values against four cancer cell lines ranging from 16.54 ± 1.22 to 63.92 ± 1.81 μM, respectively. Inhibitory rates against vascular endothelial growth factor receptor-2 (VEGFR2/KDR) kinase at 10 μM of target compounds were further carried out in this paper in order to investigate the target of these compounds. Structure-activity relationships (SARs) and docking studies indicated that the sulfonylurea unit was important to these kinds of compounds. None of the substitutions in the phenoxy group and small halogen atoms such as 2,4-difluoro substitution of the aryl group contributed to the activity. The results suggested that sulfonylurea sorafenib analogs are worthy of further study. Full article
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Open AccessArticle Purification and Partial Characterization of β-Glucosidase in Chayote (Sechium edule)
Molecules 2015, 20(10), 19372-19392; doi:10.3390/molecules201019372
Received: 17 August 2015 / Revised: 7 October 2015 / Accepted: 10 October 2015 / Published: 23 October 2015
Cited by 2 | PDF Full-text (1250 KB) | HTML Full-text | XML Full-text
Abstract
β-Glucosidase (EC 3.2.1.21) is a prominent member of the GH1 family of glycoside hydrolases. The properties of this β-glucosidase appear to include resistance to temperature, urea, and iodoacetamide, and it is activated by 2-ME, similar to other members. β-Glucosidase from chayote (Sechium
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β-Glucosidase (EC 3.2.1.21) is a prominent member of the GH1 family of glycoside hydrolases. The properties of this β-glucosidase appear to include resistance to temperature, urea, and iodoacetamide, and it is activated by 2-ME, similar to other members. β-Glucosidase from chayote (Sechium edule) was purified by ionic-interchange chromatography and molecular exclusion chromatography. Peptides detected by LC-ESI-MS/MS were compared with other β-glucosidases using the BLAST program. This enzyme is a 116 kDa protein composed of two sub-units of 58 kDa and shows homology with Cucumis sativus β-glucosidase (NCBI reference sequence XP_004154617.1), in which seven peptides were found with relative masses ranging from 874.3643 to 1587.8297. The stability of β-glucosidase depends on an initial concentration of 0.2 mg/mL of protein at pH 5.0 which decreases by 33% in a period of 30 h, and then stabilizes and is active for the next 5 days (pH 4.0 gives similar results). One hundred μg/mL β-D-glucose inhibited β-glucosidase activity by more than 50%. The enzyme had a Km of 4.88 mM with p-NPG and a Kcat of 10,000 min−1. The optimal conditions for the enzyme require a pH of 4.0 and a temperature of 50 °C. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle A Practical Route for the Preparation of 1,4,7-Triazacyclononanyl Diacetates with a Hydroxypyridinonate Pendant Arm
Molecules 2015, 20(10), 19393-19405; doi:10.3390/molecules201019393
Received: 2 September 2015 / Revised: 16 October 2015 / Accepted: 16 October 2015 / Published: 23 October 2015
Cited by 6 | PDF Full-text (781 KB) | HTML Full-text | XML Full-text
Abstract
The preparation of triazamacrocyclic hydroxypyridinonate (HOPO-TACN) derivatives as potential chelators for metals in biomedical applications was reported. The synthesis is based on a convergent synthetic approach, in which the key intermediate di-tert-butyl-2,2′-(1,4,7-triazonane-1,4-diyl) diacetate was coupled with a hydroxypyridinonate pendant arm. The
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The preparation of triazamacrocyclic hydroxypyridinonate (HOPO-TACN) derivatives as potential chelators for metals in biomedical applications was reported. The synthesis is based on a convergent synthetic approach, in which the key intermediate di-tert-butyl-2,2′-(1,4,7-triazonane-1,4-diyl) diacetate was coupled with a hydroxypyridinonate pendant arm. The method is suitable for rapid syntheses of metal chelator HOPO-TACNs of biomedical interest. Full article
(This article belongs to the Section Organic Synthesis)
Open AccessCommunication Selective Halogen-Lithium Exchange of 1,2-Dihaloarenes for Successive [2+4] Cycloadditions of Arynes and Isobenzofurans
Molecules 2015, 20(10), 19449-19462; doi:10.3390/molecules201019449
Received: 1 October 2015 / Revised: 15 October 2015 / Accepted: 20 October 2015 / Published: 23 October 2015
Cited by 2 | PDF Full-text (795 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Successive [2+4] cycloadditions of arynes and isobenzofurans by site-selective halogen-lithium exchange of 1,2-dihaloarenes were developed, allowing the rapid construction of polycyclic compounds which serve as a useful synthetic intermediates for the preparation of various polyacene derivatives. Full article
(This article belongs to the Special Issue Development and Application of Aryne Chemistry in Organic Synthesis)
Open AccessArticle Comparative Study of the Optical and Textural Properties of Tetrapyrrole Macrocycles Trapped Within ZrO2, TiO2, and SiO2 Translucent Xerogels
Molecules 2015, 20(10), 19463-19488; doi:10.3390/molecules201019463
Received: 1 August 2015 / Revised: 17 September 2015 / Accepted: 15 October 2015 / Published: 23 October 2015
Cited by 5 | PDF Full-text (10701 KB) | HTML Full-text | XML Full-text
Abstract
The entrapping of physicochemical active molecules inside mesoporous networks is an appealing field of research due to the myriad of potential applications in optics, photocatalysis, chemical sensing, and medicine. One of the most important reasons for this success is the possibility of optimizing
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The entrapping of physicochemical active molecules inside mesoporous networks is an appealing field of research due to the myriad of potential applications in optics, photocatalysis, chemical sensing, and medicine. One of the most important reasons for this success is the possibility of optimizing the properties that a free active species displays in solution but now trapped inside a solid substrate. Additionally it is possible to modulate the textural characteristics of substrates, such as pore size, specific surface area, polarity and chemical affinity of the surface, toward the physical or chemical adhesion of a variety of adsorbates. In the present document, two kinds of non-silicon metal alkoxides, Zr and Ti, are employed to prepare xerogels containing entrapped tetrapyrrolic species that could be inserted beforehand in analogue silica systems. The main goal is to develop efficient methods for trapping or binding tetrapyrrole macrocycles inside TiO2 and ZrO2 xerogels, while comparing the properties of these systems against those of the SiO2 analogues. Once the optimal synthesis conditions for obtaining translucent monolithic xerogels of ZrO2 and TiO2 networks were determined, it was confirmed that these substrates allowed the entrapment, in monomeric form, of macrocycles that commonly appear as aggregates within the SiO2 network. From these experiments, it could be determined that the average pore diameters, specific surface areas, and water sorption capacities depicted by each one of these substrates, are a consequence of their own nature combined with the particular structure of the entrapped tetrapyrrole macrocycle. Furthermore, the establishment of covalent bonds between the intruding species and the pore walls leads to the obtainment of very similar pore sizes in the three different metal oxide (Ti, Zr, and Si) substrates as a consequence of the templating effect of the encapsulated species. Full article
(This article belongs to the Special Issue Tetrapyrroles, Porphyrins and Phthalocyanines)
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Open AccessArticle Fluorescence and Docking Studies of the Interaction between Human Serum Albumin and Pheophytin
Molecules 2015, 20(10), 19526-19539; doi:10.3390/molecules201019526
Received: 28 September 2015 / Revised: 16 October 2015 / Accepted: 20 October 2015 / Published: 27 October 2015
Cited by 12 | PDF Full-text (1196 KB) | HTML Full-text | XML Full-text
Abstract
In the North of Brazil (Pará and Amazonas states) the leaves of the plant Talinum triangulare (popular: cariru) replace spinach as food. From a phytochemical point of view, they are rich in compounds of the group of pheophytins. These substances, related to
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In the North of Brazil (Pará and Amazonas states) the leaves of the plant Talinum triangulare (popular: cariru) replace spinach as food. From a phytochemical point of view, they are rich in compounds of the group of pheophytins. These substances, related to chlorophyll, have photophysical properties that give them potential application in photodynamic therapy. Human serum albumin (HSA) is one of the main endogenous vehicles for biodistribution of molecules by blood plasma. Association constants and thermodynamic parameters for the interaction of HSA with pheophytin from Talinum triangulare were studied by UV-Vis absorption, fluorescence techniques, and molecular modeling (docking). Fluorescence quenching of the HSA’s internal fluorophore (tryptophan) at temperatures 296 K, 303 K, and 310 K, resulted in values for the association constants of the order of 104 L∙mol−1, indicating a moderate interaction between the compound and the albumin. The negative values of ΔG° indicate a spontaneous process; ΔH° = 15.5 kJ∙mol−1 indicates an endothermic process of association and ΔS° = 0.145 kJ∙mol−1∙K−1 shows that the interaction between HSA and pheophytin occurs mainly by hydrophobic factors. The observed Trp fluorescence quenching is static: there is initial non-fluorescent association, in the ground state, HSA:Pheophytin. Possible solution obtained by a molecular docking study suggests that pheophytin is able to interact with HSA by means of hydrogen bonds with three lysine and one arginine residues, whereas the phytyl group is inserted in a hydrophobic pocket, close to Trp-214. Full article
(This article belongs to the Section Photochemistry)
Open AccessArticle Unique Reactivity of Transition Metal Atoms Embedded in Graphene to CO, NO, O2 and O Adsorption: A First-Principles Investigation
Molecules 2015, 20(10), 19540-19553; doi:10.3390/molecules201019540
Received: 18 September 2015 / Revised: 8 October 2015 / Accepted: 16 October 2015 / Published: 27 October 2015
Cited by 1 | PDF Full-text (2287 KB) | HTML Full-text | XML Full-text
Abstract
Taking the adsorption of CO, NO, O2 and O as probes, we investigated the electronic structure of transition metal atoms (TM, TM = Fe, Co, Ni, Cu and Zn) embedded in graphene by first-principles-based calculations. We showed that these TM atoms can
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Taking the adsorption of CO, NO, O2 and O as probes, we investigated the electronic structure of transition metal atoms (TM, TM = Fe, Co, Ni, Cu and Zn) embedded in graphene by first-principles-based calculations. We showed that these TM atoms can be effectively stabilized on monovacancy defects on graphene by forming plausible interactions with the C atoms associated with dangling bonds. These interactions not only give rise to high energy barriers for the diffusion and aggregation of the embedded TM atoms to withstand the interference of reaction environments, but also shift the energy levels of TM-d states and regulate the reactivity of the embedded TM atoms. The adsorption of CO, NO, O2 and O correlates well with the weight averaged energy level of TM-d states, showing the crucial role of interfacial TM-C interactions on manipulating the reactivity of embedded TM atoms. These findings pave the way for the developments of effective monodispersed atomic TM composites with high stability and desired performance for gas sensing and catalytic applications. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Multivariate Quantification of the Solid State Phase Composition of Co-Amorphous Naproxen-Indomethacin
Molecules 2015, 20(10), 19571-19587; doi:10.3390/molecules201019571
Received: 25 September 2015 / Revised: 19 October 2015 / Accepted: 21 October 2015 / Published: 27 October 2015
Cited by 4 | PDF Full-text (2280 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
To benefit from the optimized dissolution properties of active pharmaceutical ingredients in their amorphous forms, co-amorphisation as a viable tool to stabilize these amorphous phases is of both academic and industrial interest. Reports dealing with the physical stability and recrystallization behavior of co-amorphous
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To benefit from the optimized dissolution properties of active pharmaceutical ingredients in their amorphous forms, co-amorphisation as a viable tool to stabilize these amorphous phases is of both academic and industrial interest. Reports dealing with the physical stability and recrystallization behavior of co-amorphous systems are however limited to qualitative evaluations based on the corresponding X-ray powder diffractograms. Therefore, the objective of the study was to develop a quantification model based on X-ray powder diffractometry (XRPD), followed by a multivariate partial least squares regression approach that enables the simultaneous determination of up to four solid state fractions: crystalline naproxen, γ-indomethacin, α-indomethacin as well as co-amorphous naproxen-indomethacin. For this purpose, a calibration set that covers the whole range of possible combinations of the four components was prepared and analyzed by XRPD. In order to test the model performances, leave-one-out cross validation was performed and revealed root mean square errors of validation between 3.11% and 3.45% for the crystalline molar fractions and 5.57% for the co-amorphous molar fraction. In summary, even four solid state phases, involving one co-amorphous phase, can be quantified with this XRPD data-based approach. Full article
(This article belongs to the collection Poorly Soluble Drugs)
Open AccessArticle Elevated Expression and Pro-Inflammatory Activity of IL-36 in Patients with Systemic Lupus Erythematosus
Molecules 2015, 20(10), 19588-19604; doi:10.3390/molecules201019588
Received: 21 September 2015 / Revised: 17 October 2015 / Accepted: 21 October 2015 / Published: 27 October 2015
Cited by 7 | PDF Full-text (3707 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
We investigated the expression and proinflammatory activity of interleukin (IL)-36 in patients with systemic lupus erythematosus (SLE). The expression level of IL-36, its putative receptors and the frequency of CD19+CD24highCD27+ regulatory B (Breg) lymphocytes of peripheral blood from
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We investigated the expression and proinflammatory activity of interleukin (IL)-36 in patients with systemic lupus erythematosus (SLE). The expression level of IL-36, its putative receptors and the frequency of CD19+CD24highCD27+ regulatory B (Breg) lymphocytes of peripheral blood from 43 SLE patients and 16 normal control (NC) subjects were studied using ELISA and flow cytometry. Plasma cytokines/chemokines and ex vivo productions of cytokine/chemokine from peripheral blood mononuclear cells (PBMC) stimulated with recombinant IL-36 were determined by Luminex multiplex assay. Plasma concentrations of IL-36α, IL-36γ and the proportions of circulating IL-36R-positive CD19+ B lymphocytes in total B lymphocytes and PBMC were significantly increased in active SLE patients compared with NC (all p < 0.05). Plasma IL-36α and IL-36γ correlated positively with SLE disease activity and elevated plasma IL-10 concentration (all p < 0.05). The frequencies of circulating Breg lymphocytes in total B lymphocytes and PBMC were significantly decreased in both inactive and active SLE patients compared with NC (all p < 0.01). The frequency of Breg lymphocytes in total B lymphocytes correlated negatively with the proportion of IL-36R-positive B lymphocytes (p < 0.05). IL-36α exerted substantial proinflammatory effect in PBMC from SLE patients by inducing the production of IL-6 and CXCL8. Upon stimulation with IL-36α and IL-36γ, ex vivo productions of IL-6 and CXCL8 were significantly increased in SLE patients compared with NC (all p < 0.05). This cross-sectional study demonstrated that over expression of circulating IL-36α may exert a proinflammatory effect as observed in human SLE. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle A Simple, Effective, Green Method for the Regioselective 3-Acylation of Unprotected Indoles
Molecules 2015, 20(10), 19605-19619; doi:10.3390/molecules201019605
Received: 5 October 2015 / Revised: 22 October 2015 / Accepted: 22 October 2015 / Published: 27 October 2015
Cited by 6 | PDF Full-text (873 KB) | HTML Full-text | XML Full-text
Abstract
A fast and green method is developed for regioselective acylation of indoles in the 3-position without the need for protection of the NH position. The method is based on Friedel-Crafts acylation using acid anhydrides. The method has been optimized, and Y(OTf)3 in
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A fast and green method is developed for regioselective acylation of indoles in the 3-position without the need for protection of the NH position. The method is based on Friedel-Crafts acylation using acid anhydrides. The method has been optimized, and Y(OTf)3 in catalytic amounts is found to be the best catalyst together with the commercially available ionic liquid [BMI]BF4 (1-butyl-3-methylimidazolium tetrafluoro-borate) as solvent. The reaction is completed in a very short time using monomode microwave irradiation. The catalyst can be reused up to four times without significant loss of activity. A range of substituted indoles are investigated as substrates, and thirteen new compounds have been synthesized. Full article
(This article belongs to the Special Issue Ionic Liquids in Organic Synthesis)
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Open AccessReview Anti-Diabetic Potential of Noni: The Yin and the Yang
Molecules 2015, 20(10), 17684-17719; doi:10.3390/molecules201017684
Received: 3 May 2015 / Revised: 3 September 2015 / Accepted: 16 September 2015 / Published: 25 September 2015
Cited by 4 | PDF Full-text (823 KB) | HTML Full-text | XML Full-text
Abstract
Escalating trends of chronic diseases such as type-2 diabetes (T2D) have sparked a renewed interest in complementary and alternative medicine, including herbal products. Morinda citrifolia (noni) has been used for centuries by Pacific Islanders to treat various ailments. Commercial noni fruit juice has
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Escalating trends of chronic diseases such as type-2 diabetes (T2D) have sparked a renewed interest in complementary and alternative medicine, including herbal products. Morinda citrifolia (noni) has been used for centuries by Pacific Islanders to treat various ailments. Commercial noni fruit juice has been marketed as a dietary supplement since 1996. In 2003, the European Commission approved Tahitian noni juice as a novel food by the Health and Consumer Protection Directorate General. Among noni’s several health benefits, others and we have demonstrated the anti-diabetic effects of fermented noni fruit juice in animal models. Unfortunately, noni’s exciting journey from Polynesian medicine to the research bench does not reach its final destination of successful clinical outcomes when translated into commercial products. Noni products are perceived to be safe due to their “natural” origin. However, inadequate evidence regarding bioactive compounds, molecular targets, mechanism of action, pharmacokinetics, long-term safety, effective dosages, and/or unanticipated side effects are major roadblocks to successful translation “from bench side to bedside”. In this review we summarize the anti-diabetic potential of noni, differences between traditional and modern use of noni, along with beneficial clinical studies of noni products and challenges in clinical translation of noni’s health benefits. Full article
(This article belongs to the Special Issue 20th Anniversary of Molecules—Recent Advances in Natural Products)
Open AccessReview Phenolics and Polyphenolics from Melastomataceae Species
Molecules 2015, 20(10), 17818-17847; doi:10.3390/molecules201017818
Received: 28 June 2015 / Revised: 31 August 2015 / Accepted: 7 September 2015 / Published: 25 September 2015
Cited by 5 | PDF Full-text (4465 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The Melastomataceae family, the seventh largest flowering plants, has been studied in several fronts of natural product chemistry, including terpenoids, simple phenolics, flavonoids, quinones, lignans and their glycosides, as well as a vast range of tannins or polyphenols. This review concerns the phenolic
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The Melastomataceae family, the seventh largest flowering plants, has been studied in several fronts of natural product chemistry, including terpenoids, simple phenolics, flavonoids, quinones, lignans and their glycosides, as well as a vast range of tannins or polyphenols. This review concerns the phenolic and polyphenolic metabolites described in the literature for several genera of this family, the mode of isolation and purification, and the structure elucidation of these new natural products that has been achieved by extensive spectral analyses, including ESI-MS, 1H-, 13C-NMR spectra and two-dimensional experiments, COSY, TOCSY, J-resolved, NOESY, HMQC, DEPT, and HMBC, as well as chemical and enzymatic degradations and the chemotaxonomic meaning. Finally, a general biogenetic pathway map for ellagitannins is proposed on the bases of the most plausible free radical C-O oxidative coupling. Full article
(This article belongs to the Special Issue Recent Advances in Plant Phenolics)
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Open AccessReview Therapeutic Oligonucleotides Targeting Liver Disease: TTR Amyloidosis
Molecules 2015, 20(10), 17944-17975; doi:10.3390/molecules201017944
Received: 13 July 2015 / Revised: 23 September 2015 / Accepted: 23 September 2015 / Published: 30 September 2015
Cited by 8 | PDF Full-text (2548 KB) | HTML Full-text | XML Full-text
Abstract
The liver has become an increasingly interesting target for oligonucleotide therapy. Mutations of the gene encoding transthyretin (TTR), expressed in vast amounts by the liver, result in a complex degenerative disease, termed familial amyloid polyneuropathy (FAP). Misfolded variants of TTR are linked to
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The liver has become an increasingly interesting target for oligonucleotide therapy. Mutations of the gene encoding transthyretin (TTR), expressed in vast amounts by the liver, result in a complex degenerative disease, termed familial amyloid polyneuropathy (FAP). Misfolded variants of TTR are linked to the establishment of extracellular protein deposition in various tissues, including the heart and the peripheral nervous system. Recent progress in the chemistry and formulation of antisense (ASO) and small interfering RNA (siRNA) designed for a knockdown of TTR mRNA in the liver has allowed to address the issue of gene-specific molecular therapy in a clinical setting of FAP. The two therapeutic oligonucleotides bind to RNA in a sequence specific manner but exploit different mechanisms. Here we describe major developments that have led to the advent of therapeutic oligonucleotides for treatment of TTR-related disease. Full article
(This article belongs to the Special Issue Frontiers in Nucleic Acid Chemistry)
Open AccessReview Duchenne Muscular Dystrophy: From Diagnosis to Therapy
Molecules 2015, 20(10), 18168-18184; doi:10.3390/molecules201018168
Received: 20 July 2015 / Revised: 15 September 2015 / Accepted: 28 September 2015 / Published: 7 October 2015
Cited by 26 | PDF Full-text (1086 KB) | HTML Full-text | XML Full-text
Abstract
Duchenne muscular dystrophy (DMD) is an X-linked inherited neuromuscular disorder due to mutations in the dystrophin gene. It is characterized by progressive muscle weakness and wasting due to the absence of dystrophin protein that causes degeneration of skeletal and cardiac muscle. The molecular
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Duchenne muscular dystrophy (DMD) is an X-linked inherited neuromuscular disorder due to mutations in the dystrophin gene. It is characterized by progressive muscle weakness and wasting due to the absence of dystrophin protein that causes degeneration of skeletal and cardiac muscle. The molecular diagnostic of DMD involves a deletions/duplications analysis performed by quantitative technique such as microarray-based comparative genomic hybridization (array-CGH), Multiple Ligation Probe Assay MLPA. Since traditional methods for detection of point mutations and other sequence variants require high cost and are time consuming, especially for a large gene like dystrophin, the use of next-generation sequencing (NGS) has become a useful tool available for clinical diagnosis. The dystrophin gene is large and finely regulated in terms of tissue expression, and RNA processing and editing includes a variety of fine tuned processes. At present, there are no effective treatments and the steroids are the only fully approved drugs used in DMD therapy able to slow disease progression. In the last years, an increasing variety of strategies have been studied as a possible therapeutic approach aimed to restore dystrophin production and to preserve muscle mass, ameliorating the DMD phenotype. RNA is the most studied target for the development of clinical strategies and Antisense Oligonucleotides (AONs) are the most used molecules for RNA modulation. The identification of delivery system to enhance the efficacy and to reduce the toxicity of AON is the main purpose in this area and nanomaterials are a very promising model as DNA/RNA molecules vectors. Dystrophinopathies therefore represent a pivotal field of investigation, which has opened novel avenues in molecular biology, medical genetics and novel therapeutic options. Full article
Open AccessReview Breeding Vegetables with Increased Content in Bioactive Phenolic Acids
Molecules 2015, 20(10), 18464-18481; doi:10.3390/molecules201018464
Received: 15 July 2015 / Revised: 30 September 2015 / Accepted: 7 October 2015 / Published: 9 October 2015
Cited by 13 | PDF Full-text (786 KB) | HTML Full-text | XML Full-text
Abstract
Vegetables represent a major source of phenolic acids, powerful antioxidants characterized by an organic carboxylic acid function and which present multiple properties beneficial for human health. In consequence, developing new varieties with enhanced content in phenolic acids is an increasingly important breeding objective.
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Vegetables represent a major source of phenolic acids, powerful antioxidants characterized by an organic carboxylic acid function and which present multiple properties beneficial for human health. In consequence, developing new varieties with enhanced content in phenolic acids is an increasingly important breeding objective. Major phenolic acids present in vegetables are derivatives of cinnamic acid and to a lesser extent of benzoic acid. A large diversity in phenolic acids content has been found among cultivars and wild relatives of many vegetable crops. Identification of sources of variation for phenolic acids content can be accomplished by screening germplasm collections, but also through morphological characteristics and origin, as well as by evaluating mutations in key genes. Gene action estimates together with relatively high values for heritability indicate that selection for enhanced phenolic acids content will be efficient. Modern genomics and biotechnological strategies, such as QTL detection, candidate genes approaches and genetic transformation, are powerful tools for identification of genomic regions and genes with a key role in accumulation of phenolic acids in vegetables. However, genetically increasing the content in phenolic acids may also affect other traits important for the success of a variety. We anticipate that the combination of conventional and modern strategies will facilitate the development of a new generation of vegetable varieties with enhanced content in phenolic acids. Full article
(This article belongs to the Special Issue Recent Advances in Plant Phenolics)
Open AccessReview A Systematic Review of the Anxiolytic-Like Effects of Essential Oils in Animal Models
Molecules 2015, 20(10), 18620-18660; doi:10.3390/molecules201018620
Received: 19 August 2015 / Revised: 24 September 2015 / Accepted: 2 October 2015 / Published: 14 October 2015
Cited by 13 | PDF Full-text (821 KB) | HTML Full-text | XML Full-text
Abstract
The clinical efficacy of standardized essential oils (such as Lavender officinalis), in treating anxiety disorders strongly suggests that these natural products are an important candidate source for new anxiolytic drugs. A systematic review of essential oils, their bioactive constituents, and anxiolytic-like activity
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The clinical efficacy of standardized essential oils (such as Lavender officinalis), in treating anxiety disorders strongly suggests that these natural products are an important candidate source for new anxiolytic drugs. A systematic review of essential oils, their bioactive constituents, and anxiolytic-like activity is conducted. The essential oil with the best profile is Lavendula angustifolia, which has already been tested in controlled clinical trials with positive results. Citrus aurantium using different routes of administration also showed significant effects in several animal models, and was corroborated by different research groups. Other promising essential oils are Citrus sinensis and bergamot oil, which showed certain clinical anxiolytic actions; along with Achillea wilhemsii, Alpinia zerumbet, Citrus aurantium, and Spiranthera odoratissima, which, like Lavendula angustifolia, appear to exert anxiolytic-like effects without GABA/benzodiazepine activity, thus differing in their mechanisms of action from the benzodiazepines. The anxiolytic activity of 25 compounds commonly found in essential oils is also discussed. Full article
(This article belongs to the Section Natural Products)
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Open AccessReview Charting a Path to Success in Virtual Screening
Molecules 2015, 20(10), 18732-18758; doi:10.3390/molecules201018732
Received: 13 August 2015 / Revised: 7 October 2015 / Accepted: 12 October 2015 / Published: 15 October 2015
Cited by 8 | PDF Full-text (7136 KB) | HTML Full-text | XML Full-text
Abstract
Docking is commonly applied to drug design efforts, especially high-throughput virtual screenings of small molecules, to identify new compounds that bind to a given target. Despite great advances and successful applications in recent years, a number of issues remain unsolved. Most of the
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Docking is commonly applied to drug design efforts, especially high-throughput virtual screenings of small molecules, to identify new compounds that bind to a given target. Despite great advances and successful applications in recent years, a number of issues remain unsolved. Most of the challenges and problems faced when running docking experiments are independent of the specific software used, and can be ascribed to either improper input preparation or to the simplified approaches applied to achieve high-throughput speed. Being aware of approximations and limitations of such methods is essential to prevent errors, deal with misleading results, and increase the success rate of virtual screening campaigns. In this review, best practices and most common issues of docking and virtual screening will be discussed, covering the journey from the design of the virtual experiment to the hit identification. Full article
(This article belongs to the Special Issue Molecular Docking in Drug Design)
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Open AccessReview Polymorph Impact on the Bioavailability and Stability of Poorly Soluble Drugs
Molecules 2015, 20(10), 18759-18776; doi:10.3390/molecules201018759
Received: 11 September 2015 / Revised: 6 October 2015 / Accepted: 8 October 2015 / Published: 15 October 2015
Cited by 21 | PDF Full-text (796 KB) | HTML Full-text | XML Full-text
Abstract
Drugs with low water solubility are predisposed to poor and variable oral bioavailability and, therefore, to variability in clinical response, that might be overcome through an appropriate formulation of the drug. Polymorphs (anhydrous and solvate/hydrate forms) may resolve these bioavailability problems, but they
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Drugs with low water solubility are predisposed to poor and variable oral bioavailability and, therefore, to variability in clinical response, that might be overcome through an appropriate formulation of the drug. Polymorphs (anhydrous and solvate/hydrate forms) may resolve these bioavailability problems, but they can be a challenge to ensure physicochemical stability for the entire shelf life of the drug product. Since clinical failures of polymorph drugs have not been uncommon, and some of them have been entirely unexpected, the Food and Drug Administration (FDA) and the International Conference on Harmonization (ICH) has required preliminary and exhaustive screening studies to identify and characterize all the polymorph crystal forms for each drug. In the past, the polymorphism of many drugs was detected fortuitously or through manual time consuming methods; today, drug crystal engineering, in particular, combinatorial chemistry and high-throughput screening, makes it possible to easily and exhaustively identify stable polymorphic and/or hydrate/dehydrate forms of poorly soluble drugs, in order to overcome bioavailability related problems or clinical failures. This review describes the concepts involved, provides examples of drugs characterized by poor solubility for which polymorphism has proven important, outlines the state-of-the-art technologies and discusses the pertinent regulations. Full article
(This article belongs to the collection Poorly Soluble Drugs)
Open AccessReview Melatonin as a Potent and Inducible Endogenous Antioxidant: Synthesis and Metabolism
Molecules 2015, 20(10), 18886-18906; doi:10.3390/molecules201018886
Received: 11 September 2015 / Revised: 8 October 2015 / Accepted: 9 October 2015 / Published: 16 October 2015
Cited by 66 | PDF Full-text (1285 KB) | HTML Full-text | XML Full-text
Abstract
Melatonin is a tryptophan-derived molecule with pleiotropic activities. It is present in almost all or all organisms. Its synthetic pathway depends on the species in which it is measured. For example, the tryptophan to melatonin pathway differs in plants and animals. It is
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Melatonin is a tryptophan-derived molecule with pleiotropic activities. It is present in almost all or all organisms. Its synthetic pathway depends on the species in which it is measured. For example, the tryptophan to melatonin pathway differs in plants and animals. It is speculated that the melatonin synthetic machinery in eukaryotes was inherited from bacteria as a result of endosymbiosis. However, melatonin’s synthetic mechanisms in microorganisms are currently unknown. Melatonin metabolism is highly complex with these enzymatic processes having evolved from cytochrome C. In addition to its enzymatic degradation, melatonin is metabolized via pseudoenzymatic and free radical interactive processes. The metabolic products of these processes overlap and it is often difficult to determine which process is dominant. However, under oxidative stress, the free radical interactive pathway may be featured over the others. Because of the complexity of the melatonin degradative processes, it is expected that additional novel melatonin metabolites will be identified in future investigations. The original and primary function of melatonin in early life forms such as in unicellular organisms was as a free radical scavenger and antioxidant. During evolution, melatonin was selected as a signaling molecule to transduce the environmental photoperiodic information into an endocrine message in multicellular organisms and for other purposes as well. As an antioxidant, melatonin exhibits several unique features which differ from the classic antioxidants. These include its cascade reaction with free radicals and its capacity to be induced under moderate oxidative stress. These features make melatonin a potent endogenously-occurring antioxidant that protects organisms from catastrophic oxidative stress. Full article
(This article belongs to the Special Issue Antioxidants—A Risk-Benefit Analysis for Health)
Open AccessReview Membrane Interactions of Phytochemicals as Their Molecular Mechanism Applicable to the Discovery of Drug Leads from Plants
Molecules 2015, 20(10), 18923-18966; doi:10.3390/molecules201018923
Received: 11 September 2015 / Revised: 11 October 2015 / Accepted: 14 October 2015 / Published: 16 October 2015
Cited by 19 | PDF Full-text (1162 KB) | HTML Full-text | XML Full-text
Abstract
In addition to interacting with functional proteins such as receptors, ion channels, and enzymes, a variety of drugs mechanistically act on membrane lipids to change the physicochemical properties of biomembranes as reported for anesthetic, adrenergic, cholinergic, non-steroidal anti-inflammatory, analgesic, antitumor, antiplatelet, antimicrobial, and
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In addition to interacting with functional proteins such as receptors, ion channels, and enzymes, a variety of drugs mechanistically act on membrane lipids to change the physicochemical properties of biomembranes as reported for anesthetic, adrenergic, cholinergic, non-steroidal anti-inflammatory, analgesic, antitumor, antiplatelet, antimicrobial, and antioxidant drugs. As well as these membrane-acting drugs, bioactive plant components, phytochemicals, with amphiphilic or hydrophobic structures, are presumed to interact with biological membranes and biomimetic membranes prepared with phospholipids and cholesterol, resulting in the modification of membrane fluidity, microviscosity, order, elasticity, and permeability with the potencies being consistent with their pharmacological effects. A novel mechanistic point of view of phytochemicals would lead to a better understanding of their bioactivities, an insight into their medicinal benefits, and a strategic implication for discovering drug leads from plants. This article reviews the membrane interactions of different classes of phytochemicals by highlighting their induced changes in membrane property. The phytochemicals to be reviewed include membrane-interactive flavonoids, terpenoids, stilbenoids, capsaicinoids, phloroglucinols, naphthodianthrones, organosulfur compounds, alkaloids, anthraquinonoids, ginsenosides, pentacyclic triterpene acids, and curcuminoids. The membrane interaction’s applicability to the discovery of phytochemical drug leads is also discussed while referring to previous screening and isolating studies. Full article
(This article belongs to the Special Issue 20th Anniversary of Molecules—Recent Advances in Natural Products)
Open AccessReview Six-Membered Aromatic Polyazides: Synthesis and Application
Molecules 2015, 20(10), 19142-19171; doi:10.3390/molecules201019142
Received: 11 September 2015 / Revised: 30 September 2015 / Accepted: 13 October 2015 / Published: 21 October 2015
Cited by 9 | PDF Full-text (860 KB) | HTML Full-text | XML Full-text
Abstract
Aromatic polyazides are widely used as starting materials in organic synthesis and photochemical studies, as well as photoresists in microelectronics and as cross-linking agents in polymer chemistry. Some aromatic polyazides possess high antitumor activity, while many others are of considerable interest as high-energy
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Aromatic polyazides are widely used as starting materials in organic synthesis and photochemical studies, as well as photoresists in microelectronics and as cross-linking agents in polymer chemistry. Some aromatic polyazides possess high antitumor activity, while many others are of considerable interest as high-energy materials and precursors of high-spin nitrenes and C3N4 carbon nitride nanomaterials. The use of aromatic polyazides in click-reactions may be a new promising direction in the design of various supramolecular systems possessing interesting chemical, physical and biological properties. This review is devoted to the synthesis, properties and applications of six-membered aromatic compounds containing three and more azido groups in the ring. Full article
(This article belongs to the Special Issue Organic Azides)
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Open AccessReview Effects of Flavonoids from Food and Dietary Supplements on Glial and Glioblastoma Multiforme Cells
Molecules 2015, 20(10), 19406-19432; doi:10.3390/molecules201019406
Received: 31 July 2015 / Revised: 21 September 2015 / Accepted: 14 October 2015 / Published: 23 October 2015
Cited by 10 | PDF Full-text (892 KB) | HTML Full-text | XML Full-text
Abstract
Quercetin, catechins and proanthocyanidins are flavonoids that are prominently featured in foodstuffs and dietary supplements, and may possess anti-carcinogenic activity. Glioblastoma multiforme is the most dangerous form of glioma, a malignancy of the brain connective tissue. This review assesses molecular structures of these
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Quercetin, catechins and proanthocyanidins are flavonoids that are prominently featured in foodstuffs and dietary supplements, and may possess anti-carcinogenic activity. Glioblastoma multiforme is the most dangerous form of glioma, a malignancy of the brain connective tissue. This review assesses molecular structures of these flavonoids, their importance as components of diet and dietary supplements, their bioavailability and ability to cross the blood-brain barrier, their reported beneficial health effects, and their effects on non-malignant glial as well as glioblastoma tumor cells. The reviewed flavonoids appear to protect glial cells via reduction of oxidative stress, while some also attenuate glutamate-induced excitotoxicity and reduce neuroinflammation. Most of the reviewed flavonoids inhibit proliferation of glioblastoma cells and induce their death. Moreover, some of them inhibit pro-oncogene signaling pathways and intensify the effect of conventional anti-cancer therapies. However, most of these anti-glioblastoma effects have only been observed in vitro or in animal models. Due to limited ability of the reviewed flavonoids to access the brain, their normal dietary intake is likely insufficient to produce significant anti-cancer effects in this organ, and supplementation is needed. Full article
Open AccessReview The Multiple Roles of Microrna-223 in Regulating Bone Metabolism
Molecules 2015, 20(10), 19433-19448; doi:10.3390/molecules201019433
Received: 14 September 2015 / Revised: 13 October 2015 / Accepted: 20 October 2015 / Published: 23 October 2015
Cited by 7 | PDF Full-text (759 KB) | HTML Full-text | XML Full-text
Abstract
Bone metabolism is a lifelong process for maintaining skeletal system homeostasis, which is regulated by bone-resorbing osteoclasts and bone-forming osteoblasts. Aberrant differentiation of osteoclasts and osteoblasts leads to imbalanced bone metabolism, resulting in ossification and osteolysis diseases. MicroRNAs (miRNAs) are pivotal factors in
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Bone metabolism is a lifelong process for maintaining skeletal system homeostasis, which is regulated by bone-resorbing osteoclasts and bone-forming osteoblasts. Aberrant differentiation of osteoclasts and osteoblasts leads to imbalanced bone metabolism, resulting in ossification and osteolysis diseases. MicroRNAs (miRNAs) are pivotal factors in regulating bone metabolism via post-transcriptional inhibition of target genes. Recent studies have revealed that miR-223 exerts multiple effects on bone metabolism, especially in the processes of osteoclast and osteoblasts differentiation. In this review, we highlight the roles of miR-223 during the processes of osteoclast and osteoblast differentiation, as well as the potential clinical applications of miR-223 in bone metabolism disorders. Full article
(This article belongs to the Section Molecular Diversity)
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Open AccessReview Antioxidants of Edible Mushrooms
Molecules 2015, 20(10), 19489-19525; doi:10.3390/molecules201019489
Received: 4 September 2015 / Revised: 19 October 2015 / Accepted: 21 October 2015 / Published: 27 October 2015
Cited by 21 | PDF Full-text (1537 KB) | HTML Full-text | XML Full-text
Abstract
Oxidative stress caused by an imbalanced metabolism and an excess of reactive oxygen species (ROS) lead to a range of health disorders in humans. Our endogenous antioxidant defense mechanisms and our dietary intake of antioxidants potentially regulate our oxidative homeostasis. Numerous synthetic antioxidants
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Oxidative stress caused by an imbalanced metabolism and an excess of reactive oxygen species (ROS) lead to a range of health disorders in humans. Our endogenous antioxidant defense mechanisms and our dietary intake of antioxidants potentially regulate our oxidative homeostasis. Numerous synthetic antioxidants can effectively improve defense mechanisms, but because of their adverse toxic effects under certain conditions, preference is given to natural compounds. Consequently, the requirements for natural, alternative sources of antioxidant foods identified in edible mushrooms, as well as the mechanistic action involved in their antioxidant properties, have increased rapidly. Chemical composition and antioxidant potential of mushrooms have been intensively studied. Edible mushrooms might be used directly in enhancement of antioxidant defenses through dietary supplementation to reduce the level of oxidative stress. Wild or cultivated, they have been related to significant antioxidant properties due to their bioactive compounds, such as polyphenols, polysaccharides, vitamins, carotenoids and minerals. Antioxidant and health benefits, observed in edible mushrooms, seem an additional reason for their traditional use as a popular delicacy food. This review discusses the consumption of edible mushrooms as a powerful instrument in maintaining health, longevity and life quality. Full article
(This article belongs to the Special Issue Antioxidants—A Risk-Benefit Analysis for Health)
Open AccessReview Starch Modification by Organic Acids and Their Derivatives: A Review
Molecules 2015, 20(10), 19554-19570; doi:10.3390/molecules201019554
Received: 23 August 2015 / Revised: 14 October 2015 / Accepted: 15 October 2015 / Published: 27 October 2015
Cited by 5 | PDF Full-text (936 KB) | HTML Full-text | XML Full-text
Abstract
Starch has been an inexhaustible subject of research for many decades. It is an inexpensive, readily-available material with extensive application in the food and processing industry. Researchers are continually trying to improve its properties by different modification procedures and expand its application. What
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Starch has been an inexhaustible subject of research for many decades. It is an inexpensive, readily-available material with extensive application in the food and processing industry. Researchers are continually trying to improve its properties by different modification procedures and expand its application. What is mostly applied in this view are their chemical modifications, among which organic acids have recently drawn the greatest attention, particularly with respect to the application of starch in the food industry. Namely, organic acids naturally occur in many edible plants and many of them are generally recognized as safe (GRAS), which make them ideal modification agents for starch intended for the food industry. The aim of this review is to give a short literature overview of the progress made in the research of starch esterification, etherification, cross-linking, and dual modification with organic acids and their derivatives. Full article
(This article belongs to the Section Natural Products)
Open AccessReview Supramolecular Complexation of Carbohydrates for the Bioavailability Enhancement of Poorly Soluble Drugs
Molecules 2015, 20(10), 19620-19646; doi:10.3390/molecules201019620
Received: 15 September 2015 / Revised: 16 October 2015 / Accepted: 22 October 2015 / Published: 27 October 2015
Cited by 11 | PDF Full-text (1158 KB) | HTML Full-text | XML Full-text
Abstract
In this review, a comprehensive overview of advances in the supramolecular complexes of carbohydrates and poorly soluble drugs is presented. Through the complexation process, poorly soluble drugs could be efficiently delivered to their desired destinations. Carbohydrates, the most abundant biomolecules, have diverse physicochemical
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In this review, a comprehensive overview of advances in the supramolecular complexes of carbohydrates and poorly soluble drugs is presented. Through the complexation process, poorly soluble drugs could be efficiently delivered to their desired destinations. Carbohydrates, the most abundant biomolecules, have diverse physicochemical properties owing to their inherent three-dimensional structures, hydrogen bonding, and molecular recognition abilities. In this regard, oligosaccharides and their derivatives have been utilized for the bioavailability enhancement of hydrophobic drugs via increasing the solubility or stability. By extension, polysaccharides and their derivatives can form self-assembled architectures with poorly soluble drugs and have shown increased bioavailability in terms of the sustained or controlled drug release. These supramolecular systems using carbohydrate will be developed consistently in the field of pharmaceutical and medical application. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessCorrection Correction: Gomez, T., et al. Imaging the Ultrafast Photoelectron Transfer Process in Alizarin-TiO2. Molecules 2015, 20, 13830–13853
Molecules 2015, 20(10), 19027-19029; doi:10.3390/molecules201019027
Received: 10 October 2015 / Accepted: 12 October 2015 / Published: 20 October 2015
PDF Full-text (606 KB) | HTML Full-text | XML Full-text
Abstract
The author wishes to make the following correction to this paper [1]. Due to mislabeling, please replace: [...] Full article
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