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Molecules, Volume 22, Issue 12 (December 2017)

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Open AccessArticle Access to New Cytotoxic Quinone-Amino Acid Conjugates Linked through A Vinylic Spacer from 2-Acylnaphthoquinones and Methyl 3-Aminocrotonate
Molecules 2017, 22(12), 2281; https://doi.org/10.3390/molecules22122281
Received: 28 November 2017 / Revised: 16 December 2017 / Accepted: 19 December 2017 / Published: 20 December 2017
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Abstract
The reaction of 2-acetyl- and 2-benzoyl-1,4-naphthoquinone with (Z)-methyl 3-(hydroxymethyl)aminocrotonate proceeds through a formal [3+3] process to yield the corresponding 1,2-dihydrobenzisoquinolinequinones in 63% and 72% yield, respectively. The reactions of 2-acyl-1,4-naphthoquinone with enaminones, derived from diverse l- and d-amino acid
[...] Read more.
The reaction of 2-acetyl- and 2-benzoyl-1,4-naphthoquinone with (Z)-methyl 3-(hydroxymethyl)aminocrotonate proceeds through a formal [3+3] process to yield the corresponding 1,2-dihydrobenzisoquinolinequinones in 63% and 72% yield, respectively. The reactions of 2-acyl-1,4-naphthoquinone with enaminones, derived from diverse l- and d-amino acid methyl esters, produced the corresponding naphthoquinone amino acids conjugates bonded through a vinyl spacer in the yields range 40–71%. The presence of not-separable isomers of the naphthoquinone amino acids conjugates in the 1H- and 13C-NMR spectra is explained by the existence of conformational isomers generated by hindered rotation of the substituent bonded to the quinone double bond. These new naphthoquinone amino acids conjugates were screened in vitro on normal and cancer cell lines and showed moderate cytotoxic activities. Full article
(This article belongs to the Section Organic Chemistry)
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Open AccessArticle Adsorption of Cd (II) on Modified Granular Activated Carbons: Isotherm and Column Study
Molecules 2017, 22(12), 2280; https://doi.org/10.3390/molecules22122280
Received: 15 November 2017 / Revised: 13 December 2017 / Accepted: 14 December 2017 / Published: 20 December 2017
Cited by 2 | PDF Full-text (1462 KB) | HTML Full-text | XML Full-text
Abstract
In this work, equilibrium and dynamic adsorption tests of cadmium Cd (II) on activated carbons derived from different oxidation treatments (with either HNO3, H2O2, or NaOCl, corresponding to GACoxN, GACoxP, and GACoxCl samples) are presented. The oxidation
[...] Read more.
In this work, equilibrium and dynamic adsorption tests of cadmium Cd (II) on activated carbons derived from different oxidation treatments (with either HNO3, H2O2, or NaOCl, corresponding to GACoxN, GACoxP, and GACoxCl samples) are presented. The oxidation treatments determined an increase in the surface functional groups (mainly the acidic ones) and a decrease in the pHPZC (except for the GACoxCl sample). A slight alteration of the textural parameters was also observed, which was more significant for the GACoxCl sample, in terms of a decrease of both Brunauer-Emmett-Teller (BET) surface area and micropore volume. Adsorption isotherms were determined for all the adsorbents and a significant increase in the adsorption performances of the oxidized samples with respect to the parent material was observed. The performances ranking was GACoxCl > GACoxP > GACoxN > GAC, likely due to the chemical surface properties of the adsorbents. Dynamic tests in a fixed bed column were carried out in terms of breakthrough curves at constant Cd inlet concentration and flow rate. GACoxCl and GACoxN showed a significantly higher value of the breakpoint time, likely due to the higher adsorption capacity. Finally, the dynamic tests were analyzed in light of a kinetic model. In the adopted experimental conditions, the results showed that mass transfer is controlled by internal pore diffusion, in which surface diffusion plays a major role. Full article
(This article belongs to the Section Green Chemistry)
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Open AccessArticle Labdane-Type Diterpenes, Galangalditerpenes A–C, with Melanogenesis Inhibitory Activity from the Fruit of Alpinia galanga
Molecules 2017, 22(12), 2279; https://doi.org/10.3390/molecules22122279
Received: 24 November 2017 / Revised: 16 December 2017 / Accepted: 18 December 2017 / Published: 20 December 2017
Cited by 3 | PDF Full-text (1996 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In our continuing study of biologically active natural products from the fruit of Alpinia galanga (Zingiberaceae), we newly isolated three new labdane-type diterpenes, termed galangalditerpenes A–C (13), along with four known sesquiterpenes (47) and two
[...] Read more.
In our continuing study of biologically active natural products from the fruit of Alpinia galanga (Zingiberaceae), we newly isolated three new labdane-type diterpenes, termed galangalditerpenes A–C (13), along with four known sesquiterpenes (47) and two diterpenes (8 and 9). The stereostructures of 13 were elucidated on the basis of their spectroscopic properties. The melanogenesis inhibitory activities in theophylline-stimulated murine B16 melanoma 4A5 cells of these isolates, including the new diterpenes (13, IC50 = 4.4, 8.6, and 4.6 μM, respectively), were found to be more than 6–87-fold higher than that of arbutin (174 μM), a commercially available positive control. Full article
(This article belongs to the Special Issue Diversity of Terpenoids)
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Open AccessCommunication A Water Cluster Conduit in Crystal
Molecules 2017, 22(12), 2278; https://doi.org/10.3390/molecules22122278
Received: 25 October 2017 / Revised: 13 December 2017 / Accepted: 14 December 2017 / Published: 20 December 2017
Cited by 1 | PDF Full-text (1352 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The crystal structure of compound (1), [CuCl(phen)(H2NCH2COO)]∙4H2O, reveals an unusual hydrogen-bond water cluster aggregate T6(2)6(2). Four water molecules in (1) form an isolated water cluster, [(H2O)14]n, resembling
[...] Read more.
The crystal structure of compound (1), [CuCl(phen)(H2NCH2COO)]∙4H2O, reveals an unusual hydrogen-bond water cluster aggregate T6(2)6(2). Four water molecules in (1) form an isolated water cluster, [(H2O)14]n, resembling a “phenanthro-[1,2]phenanthrene polymer structure shape” along the ac plane. The two face-face parallel [(H2O)14]n planes are bridged by Cl atoms in [CuCl(phen) (H2NCH2COO)] with a strong O-H∙∙∙Cl hydrogen bond to form a water cluster conduit. Full article
(This article belongs to the Section Inorganic Chemistry)
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Open AccessReview PP2A as the Main Node of Therapeutic Strategies and Resistance Reversal in Triple-Negative Breast Cancer
Molecules 2017, 22(12), 2277; https://doi.org/10.3390/molecules22122277
Received: 3 November 2017 / Revised: 7 December 2017 / Accepted: 19 December 2017 / Published: 20 December 2017
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Abstract
Triple negative breast cancer (TNBC), is defined as a type of tumor lacking the expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). The ER, PR and HER2 are usually the molecular therapeutic targets for breast
[...] Read more.
Triple negative breast cancer (TNBC), is defined as a type of tumor lacking the expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). The ER, PR and HER2 are usually the molecular therapeutic targets for breast cancers, but they are ineffective for TNBC because of their negative expressions, so chemotherapy is currently the main treatment strategy in TNBC. However, drug resistance remains a major impediment to TNBC chemotherapeutic treatment. Recently, the protein phosphatase 2A (PP2A) has been found to regulate the phosphorylation of some substrates involved in the relevant target of TNBC, such as cell cycle control, DNA damage responses, epidermal growth factor receptor, immune modulation and cell death resistance, which may be the effective therapeutic strategies or influence drug sensitivity to TNBCs. Furthermore, PP2A has also been found that could induce ER re-expression in ER-negative breast cancer cells, and which suggests PP2A could promote the sensitivity of tamoxifen to TNBCs as a resistance reversal agent. In this review, we will summarize the potential therapeutic value of PP2A as the main node in developing targeting agents, disrupting resistance or restoring drug sensitivity in TNBC. Full article
(This article belongs to the Special Issue Counteracting Drug Resistant Mechanisms in Cancer)
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Open AccessArticle UPLC Quantitative Analysis of Multi-Components by Single Marker and Quality Evaluation of Polygala tenuifolia Wild. Extracts
Molecules 2017, 22(12), 2276; https://doi.org/10.3390/molecules22122276
Received: 16 November 2017 / Revised: 11 December 2017 / Accepted: 15 December 2017 / Published: 20 December 2017
Cited by 2 | PDF Full-text (2668 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The quality control of Polygala tenuifolia Wild. is a major challenge in its clinical application. In this paper, a new strategy for the quality evaluation of P. tenuifolia extracts was verified through reverse-phase ultra-performance liquid chromatography (UPLC). The quantitative analysis of multi-components by
[...] Read more.
The quality control of Polygala tenuifolia Wild. is a major challenge in its clinical application. In this paper, a new strategy for the quality evaluation of P. tenuifolia extracts was verified through reverse-phase ultra-performance liquid chromatography (UPLC). The quantitative analysis of multi-components by a single marker (QAMS) was conducted with 3,6′-disinapoyl sucrose as an internal reference substance. Eight components (i.e., sibiricose A5, sibiricose A6, glomeratose A, tenuifoliside A, tenuifoliside B, tenuifoliside C, sibiricaxanthone B, and polygalaxanthone III) were determined based on the relative correction factors. The concentrations of these components were also determined by applying a conventional external standard method. The cosine value confirmed the consistency of the two methods (cosine ratio value >0.999920). Hierarchical cluster analysis, radar plots, and discriminant analysis were performed to classify 23 batches of P. tenuifolia extracts from Shanxi, Hebei, and Shaanxi in China. Results revealed that QAMS combined with radar plots and multivariate data analysis could accurately measure and clearly distinguish the different quality samples of P. tenuifolia. Hence, QAMS is a feasible and promising method for the quality control of P. tenuifolia. Full article
(This article belongs to the Section Natural Products Chemistry)
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Open AccessArticle Increasing Antioxidant Activity and Protein Digestibility in Phaseolus vulgaris and Avena sativa by Fermentation with the Pleurotus ostreatus Fungus
Molecules 2017, 22(12), 2275; https://doi.org/10.3390/molecules22122275
Received: 7 November 2017 / Revised: 12 December 2017 / Accepted: 16 December 2017 / Published: 20 December 2017
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Abstract
The aim of the research was to determine the impact of fermentation with Pleurotus ostreatus on kidney beans, black beans, and oats. The results indicate that the fungus has a positive effect on the substrates when compared to the controls. The antioxidant activity
[...] Read more.
The aim of the research was to determine the impact of fermentation with Pleurotus ostreatus on kidney beans, black beans, and oats. The results indicate that the fungus has a positive effect on the substrates when compared to the controls. The antioxidant activity (39.5% on kidney beans and 225% on oats in relation to the controls) and content of total polyphenols (kidney beans three times higher regarding the controls) increased significantly by the presence of the fungus mycelium, even after simulated digestion. There was a significant increase in protein digestibility (from 39.99 to 48.13% in black beans, 44.06 to 69.01% in kidney beans, and 63.25 to 70.01% in oats) and a decrease of antinutrient tannins (from 65.21 to 22.07 mg in black beans, 35.54 to 23.37 in kidney beans, and 55.67 to 28.11 in oats) as well as an increase in the contents of some essential amino acids. Overall, this fermentation treatment with Pleurotus ostreatus improved the nutritional quality of cereals and legumes, making them potential ingredients for the elaboration and/or fortification of foods for human nutrition. Full article
(This article belongs to the Special Issue Extractable and Non-Extractable Antioxidants)
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Open AccessArticle Zinc Ion Removal on Hybrid Pectin-Based Beads Containing Modified Poly(Methyl Methacrylate) Waste
Molecules 2017, 22(12), 2274; https://doi.org/10.3390/molecules22122274
Received: 16 November 2017 / Revised: 13 December 2017 / Accepted: 16 December 2017 / Published: 20 December 2017
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Abstract
A new hybrid sorbent in the form of round beads containing modified poly(methyl methacrylate) (PMMA) waste immobilized in pectin and crosslinked with calcium ions was prepared. A previously obtained and characterized powdered poly(methyl methacrylate)–based sorbent was used. Batch and column studies on the
[...] Read more.
A new hybrid sorbent in the form of round beads containing modified poly(methyl methacrylate) (PMMA) waste immobilized in pectin and crosslinked with calcium ions was prepared. A previously obtained and characterized powdered poly(methyl methacrylate)–based sorbent was used. Batch and column studies on the new material’s sorption-desorption properties were performed. Two kinetic models (pseudo-first- and pseudo-second-order) and three isotherms (Langmuir, Langmuir bisite and Freundlich) were used to describe the results. Breakthrough and elution curves were also obtained. Nitric, hydrochloric, and sulfuric acid of various concentrations were used in the desorption studies. Higher sorption affinity of zinc(II) ions to hybrid sorbent than to pectin alone, reflected by higher values of the Langmuir and Freundlich model parameters, was observed. The maximum sorption capacities, calculated based on the best-fitted models, were 50.2 mg/g (Langmuir bisite) and 42.2 mg/g (Langmuir) for hybrid and only pectin beads, respectively. The stripping of Zn ions using 0.1 M solutions of mineral acids was similarly effective in the case of both sorbents. The mass balance calculated for the column studies showed about 100% recovery of zinc in a sorption-desorption cycle. By applying the hybrid sorbent under the studied conditions it is possible to purify Zn in water to the level permitted by law and concentrate Zn(II) ions by about 60 times. Full article
(This article belongs to the Special Issue Polysaccharide-based Materials)
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Open AccessArticle Modulation of the Selectivity in Anions Recognition Processes by Combining Hydrogen- and Halogen-Bonding Interactions
Molecules 2017, 22(12), 2273; https://doi.org/10.3390/molecules22122273
Received: 17 November 2017 / Revised: 11 December 2017 / Accepted: 18 December 2017 / Published: 20 December 2017
Cited by 1 | PDF Full-text (2523 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Most of the halogen bonding receptors for anions described use halogen bonding binding sites solely in the anion recognition process; only a few examples report the study of anion receptors in which the halogen bonding interaction has been used in combination with any
[...] Read more.
Most of the halogen bonding receptors for anions described use halogen bonding binding sites solely in the anion recognition process; only a few examples report the study of anion receptors in which the halogen bonding interaction has been used in combination with any other non-covalent interaction. With the aims to extend the knowledge in the behaviour of this kind of mixed receptors, we report here the synthesis and the anion recognition and sensing properties of a new halogen- and hydrogen- bonding receptor which binds anions by the cooperation of both non-covalent interactions. Fluorescence studies showed that the behaviour observed in the anion recognition sensing is similar to the one previously described for the halogen analogue and is quite different to the hydrogen one. On the other hand, the association constants obtained by 1H-NMR data demonstrate that the mixed halogen- and hydrogen-bonding receptor is more selective for SO42− anion than the halogen or hydrogen analogues. Full article
(This article belongs to the Special Issue Halogen Bonds and Beyond)
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Open AccessArticle Activation of Recombinantly Expressed l-Amino Acid Oxidase from Rhizoctonia solani by Sodium Dodecyl Sulfate
Molecules 2017, 22(12), 2272; https://doi.org/10.3390/molecules22122272
Received: 10 November 2017 / Revised: 15 December 2017 / Accepted: 18 December 2017 / Published: 20 December 2017
Cited by 1 | PDF Full-text (3314 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
l-Amino acid oxidases (l-AAO) catalyze the oxidative deamination of l-amino acids to the corresponding α-keto acids. The non-covalently bound cofactor FAD is reoxidized by oxygen under formation of hydrogen peroxide. We expressed an active l-AAO from the fungus
[...] Read more.
l-Amino acid oxidases (l-AAO) catalyze the oxidative deamination of l-amino acids to the corresponding α-keto acids. The non-covalently bound cofactor FAD is reoxidized by oxygen under formation of hydrogen peroxide. We expressed an active l-AAO from the fungus Rhizoctonia solani as a fusion protein in E. coli. Treatment with small amounts of the detergent sodium dodecyl sulfate (SDS) stimulated the activity of the enzyme strongly. Here, we investigated whether other detergents and amphiphilic molecules activate 9His-rsLAAO1. We found that 9His-rsLAAO1 was also activated by sodium tetradecyl sulfate. Other detergents and fatty acids were not effective. Moreover, effects of SDS on the oligomerization state and the protein structure were analyzed. Native and SDS-activated 9His-rsLAAO1 behaved as dimers by size-exclusion chromatography. SDS treatment induced an increase in hydrodynamic radius as observed by size-exclusion chromatography and dynamic light scattering. The activated enzyme showed accelerated thermal inactivation and an exposure of additional protease sites. Changes in tryptophan fluorescence point to a more hydrophilic environment. Moreover, FAD fluorescence increased and a lower concentration of sulfites was sufficient to form adducts with FAD. Taken together, these data point towards a more open conformation of SDS-activated l-amino acid oxidase facilitating access to the active site. Full article
(This article belongs to the Special Issue Flavoenzymes)
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Open AccessArticle Thermal and Antioxidant Properties of Polysaccharides Sequentially Extracted from Mulberry Leaves (Morus alba L.)
Molecules 2017, 22(12), 2271; https://doi.org/10.3390/molecules22122271
Received: 30 November 2017 / Revised: 16 December 2017 / Accepted: 17 December 2017 / Published: 20 December 2017
Cited by 10 | PDF Full-text (2762 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Polysaccharides from natural plant products are gaining considerable attention due to their multi-faceted health effects, as well their functional applications in food production. We reported the sequential extraction of mulberry leaf polysaccharides (MLPs) with hot buffer (HBSS), chelating agent (CHSS), dilute alkali (DASS)
[...] Read more.
Polysaccharides from natural plant products are gaining considerable attention due to their multi-faceted health effects, as well their functional applications in food production. We reported the sequential extraction of mulberry leaf polysaccharides (MLPs) with hot buffer (HBSS), chelating agent (CHSS), dilute alkali (DASS) and concentrated alkali (CASS), in order to obtain polysaccharide fractions. Monosaccharide analysis proved that galactose (27.07%) and arabinose (25.99%) were the major sugars in HBSS, whereas arabinose (30.55%) was the major sugar in CHSS, and glucose was the major sugar in DASS (24.96%) and CASS (27.51%). The molecular weights of the polysaccharide fractions were 7.812 × 103 (HBSS), 3.279 × 103 (CHSS), 6.912 × 103 (DASS), and 1.408 × 103 kDa (CASS). HBSS and CASS showed the largest peak temperature and the highest endothermic enthalpy, respectively. Different antioxidant assays showed that the MLPs possessed appreciable antioxidant activities in a dose-dependent manner. At 5 mg/mL, HBSS and DASS possessed the largest 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) radical scavenging activity (96.82%). HBSS exhibited the highest reducing power, and DASS rendered the strongest ABTS radical scavenging activity (99.69%). CHSS performed the best hydroxyl radical scavenging activity (64.22%) and Fe2+-chelating ability (96.36%). Our results suggested that MLPs could be a promising source of natural antioxidants for use in the food, pharmaceutical, and cosmetic industries. Full article
(This article belongs to the Special Issue Polysaccharide-based Materials)
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Open AccessArticle Novel Mixed-Type Inhibitors of Protein Tyrosine Phosphatase 1B. Kinetic and Computational Studies
Molecules 2017, 22(12), 2262; https://doi.org/10.3390/molecules22122262
Received: 21 November 2017 / Revised: 13 December 2017 / Accepted: 16 December 2017 / Published: 20 December 2017
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Abstract
The Atlas of Diabetes reports 415 million diabetics in the world, a number that has surpassed in half the expected time the twenty year projection. Type 2 diabetes is the most frequent form of the disease; it is characterized by a defect in
[...] Read more.
The Atlas of Diabetes reports 415 million diabetics in the world, a number that has surpassed in half the expected time the twenty year projection. Type 2 diabetes is the most frequent form of the disease; it is characterized by a defect in the secretion of insulin and a resistance in its target organs. In the search for new antidiabetic drugs, one of the principal strategies consists in promoting the action of insulin. In this sense, attention has been centered in the protein tyrosine phosphatase 1B (PTP1B), a protein whose overexpression or increase of its activity has been related in many studies with insulin resistance. In the present work, a chemical library of 250 compounds was evaluated to determine their inhibition capability on the protein PTP1B. Ten molecules inhibited over the 50% of the activity of the PTP1B, the three most potent molecules were selected for its characterization, reporting Ki values of 5.2, 4.2 and 41.3 µM, for compounds 1, 2, and 3, respectively. Docking and molecular dynamics studies revealed that the three inhibitors made interactions with residues at the secondary binding site to phosphate, exclusive for PTP1B. The data reported here support these compounds as hits for the design more potent and selective inhibitors against PTP1B in the search of new antidiabetic treatment. Full article
(This article belongs to the Special Issue Protein-Tyrosine Phosphatase Inhibitors)
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Open AccessArticle Optimization Technology of the LHS-1 Strain for Degrading Gallnut Water Extract and Appraisal of Benzene Ring Derivatives from Fermented Gallnut Water Extract Pyrolysis by Py-GC/MS
Molecules 2017, 22(12), 2253; https://doi.org/10.3390/molecules22122253
Received: 31 October 2017 / Revised: 9 December 2017 / Accepted: 11 December 2017 / Published: 20 December 2017
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Abstract
Gallnut water extract (GWE) enriches 80~90% of gallnut tannic acid (TA). In order to study the biodegradation of GWE into gallic acid (GA), the LHS-1 strain, a variant of Aspergillus niger, was chosen to determine the optimal degradation parameters for maximum production
[...] Read more.
Gallnut water extract (GWE) enriches 80~90% of gallnut tannic acid (TA). In order to study the biodegradation of GWE into gallic acid (GA), the LHS-1 strain, a variant of Aspergillus niger, was chosen to determine the optimal degradation parameters for maximum production of GA by the response surface method. Pyrolysis–gas chromatography–mass spectrometry (Py-GC/MS) was first applied to appraise benzene ring derivatives of fermented GWE (FGWE) pyrolysis by comparison with the pyrolytic products of a tannic acid standard sample (TAS) and GWE. The results showed that optimum conditions were at 31 °C and pH of 5, with a 50-h incubation period and 0.1 g·L−1 of TA as substrate. The maximum yields of GA and tannase were 63~65 mg·mL−1 and 1.17 U·mL−1, respectively. Over 20 kinds of compounds were identified as linear hydrocarbons and benzene ring derivatives based on GA and glucose. The key benzene ring derivatives were 3,4,5-trimethoxybenzoic acid methyl ester, 3-methoxy-1,2-benzenediol, and 4-hydroxy-3,5-dimethoxy-benzoic acid hydrazide. Full article
(This article belongs to the Section Chemical Biology)
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Open AccessArticle Calli Essential Oils Synergize with Lawsone against Multidrug Resistant Pathogens
Molecules 2017, 22(12), 2223; https://doi.org/10.3390/molecules22122223
Received: 30 October 2017 / Revised: 9 December 2017 / Accepted: 12 December 2017 / Published: 20 December 2017
PDF Full-text (3313 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The fast development of multi-drug resistant (MDR) organisms increasingly threatens global health and well-being. Plant natural products have been known for centuries as alternative medicines that can possess pharmacological characteristics, including antimicrobial activities. The antimicrobial activities of essential oil (Calli oil) extracted from
[...] Read more.
The fast development of multi-drug resistant (MDR) organisms increasingly threatens global health and well-being. Plant natural products have been known for centuries as alternative medicines that can possess pharmacological characteristics, including antimicrobial activities. The antimicrobial activities of essential oil (Calli oil) extracted from the Calligonum comosum plant by hydro-steam distillation was tested either alone or when combined with lawsone, a henna plant naphthoquinone, against MDR microbes. Lawsone showed significant antimicrobial activities against MDR pathogens in the range of 200–300 µg/mL. Furthermore, Calli oil showed significant antimicrobial activities against MDR bacteria in the range of 180–200 µg/mL, Candida at 220–240 µg/mL and spore-forming Rhizopus fungus at 250 µg/mL. Calli oil’s inhibition effect on Rhizopus, the major cause of the lethal infection mucormycosis, stands for 72 h, followed by an extended irreversible white sporulation effect. The combination of Calli oil with lawsone enhanced the antimicrobial activities of each individual alone by at least three-fold, while incorporation of both natural products in a liposome reduced their toxicity by four- to eight-fold, while maintaining the augmented efficacy of the combination treatment. We map the antimicrobial activity of Calli oil to its major component, a benzaldehyde derivative. The findings from this study demonstrate that formulations containing essential oils have the potential in the future to overcome antimicrobial resistance. Full article
(This article belongs to the Special Issue Essential Oils as Antimicrobial and Anti-infectious Agents)
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Open AccessArticle A Chemical Genetics Strategy That Identifies Small Molecules Which Induce the Triple Response in Arabidopsis
Molecules 2017, 22(12), 2270; https://doi.org/10.3390/molecules22122270
Received: 22 October 2017 / Revised: 10 December 2017 / Accepted: 13 December 2017 / Published: 19 December 2017
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Abstract
To explore small molecules with ethylene-like biological activity, we conducted a triple response-based assay system for chemical library screening. Among 9600 compounds, we found N-[(1,3,5-trimethyl-1H-pyrazol-4-yl)methyl]-N-methyl-2-naphthalenesulfonamide (EH-1) displayed promising biological activity on inducing a triple response in
[...] Read more.
To explore small molecules with ethylene-like biological activity, we conducted a triple response-based assay system for chemical library screening. Among 9600 compounds, we found N-[(1,3,5-trimethyl-1H-pyrazol-4-yl)methyl]-N-methyl-2-naphthalenesulfonamide (EH-1) displayed promising biological activity on inducing a triple response in Arabidopsis seedlings. Chemical synthesis and structure–activity relationship (SAR) analysis of EH-1 analogues with different substitution patterns on the phenyl ring structure of the sulfonamide group indicated that 3,4-dichloro-N-methyl-N-(1,3,5-trimethyl-1H-pyrazol-4-yl-methyl)benzenesulfonamide (8) exhibits the most potent biological activity. To determine the mechanism of action, we conducted RNA sequencing (RNA-Seq) analysis of the effect of EH-1 and 1-aminocyclopropane-1-carboxylate (ACC), the precursor of ethylene biosynthesis, following the quantitative real-time polymerase chain reaction (RT-PCR) confirmation. Data obtained from RNA-Seq analysis indicated that EH-1 and ACC significantly induced the expression of 39 and 48 genes, respectively (above 20 fold of control), among which five genes are up-regulated by EH-1 as well as by ACC. We also found 67 and 32 genes that are significantly down-regulated, respectively, among which seven genes are in common. For quantitative RT-PCR analysis. 12 up-regulated genes were selected from the data obtained from RNA-Seq analysis. We found a good correlation of quantitative RT-PCR analysis and RNA-Seq analysis. Based on these results, we conclude that the action mechanism of EH-1 on inducing triple response in Arabidopsis is different from that of ACC. Full article
(This article belongs to the Special Issue Sulfonamides)
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Open AccessReview Vanadium Compounds as PTP Inhibitors
Molecules 2017, 22(12), 2269; https://doi.org/10.3390/molecules22122269
Received: 30 November 2017 / Revised: 14 December 2017 / Accepted: 15 December 2017 / Published: 19 December 2017
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Abstract
Phosphotyrosine signaling is regulated by the opposing actions of protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs). Here we discuss the potential of vanadium derivatives as PTP enzyme inhibitors and metallotherapeutics. We describe how vanadate in the V oxidized state is thought
[...] Read more.
Phosphotyrosine signaling is regulated by the opposing actions of protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs). Here we discuss the potential of vanadium derivatives as PTP enzyme inhibitors and metallotherapeutics. We describe how vanadate in the V oxidized state is thought to inhibit PTPs, thus acting as a pan-inhibitor of this enzyme superfamily. We discuss recent developments in the biological and biochemical actions of more complex vanadium derivatives, including decavanadate and in particular the growing number of oxidovanadium compounds with organic ligands. Pre-clinical studies involving these compounds are discussed in the anti-diabetic and anti-cancer contexts. Although in many cases PTP inhibition has been implicated, it is also clear that many such compounds have further biochemical effects in cells. There also remain concerns surrounding off-target toxicities and long-term use of vanadium compounds in vivo in humans, hindering their progress through clinical trials. Despite these current misgivings, interest in these chemicals continues and many believe they could still have therapeutic potential. If so, we argue that this field would benefit from greater focus on improving the delivery and tissue targeting of vanadium compounds in order to minimize off-target toxicities. This may then harness their full therapeutic potential. Full article
(This article belongs to the Special Issue Protein-Tyrosine Phosphatase Inhibitors)
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Open AccessReview Quinoline-Based Hybrid Compounds with Antimalarial Activity
Molecules 2017, 22(12), 2268; https://doi.org/10.3390/molecules22122268
Received: 7 November 2017 / Revised: 11 December 2017 / Accepted: 11 December 2017 / Published: 19 December 2017
Cited by 2 | PDF Full-text (1944 KB) | HTML Full-text | XML Full-text
Abstract
The application of quinoline-based compounds for the treatment of malaria infections is hampered by drug resistance. Drug resistance has led to the combination of quinolines with other classes of antimalarials resulting in enhanced therapeutic outcomes. However, the combination of antimalarials is limited by
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The application of quinoline-based compounds for the treatment of malaria infections is hampered by drug resistance. Drug resistance has led to the combination of quinolines with other classes of antimalarials resulting in enhanced therapeutic outcomes. However, the combination of antimalarials is limited by drug-drug interactions. In order to overcome the aforementioned factors, several researchers have reported hybrid compounds prepared by reacting quinoline-based compounds with other compounds via selected functionalities. This review will focus on the currently reported quinoline-based hybrid compounds and their preclinical studies. Full article
(This article belongs to the Special Issue Emerging Drug Discovery Approaches against Infectious Diseases)
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Open AccessReview Amikacin: Uses, Resistance, and Prospects for Inhibition
Molecules 2017, 22(12), 2267; https://doi.org/10.3390/molecules22122267
Received: 27 November 2017 / Revised: 13 December 2017 / Accepted: 14 December 2017 / Published: 19 December 2017
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Abstract
Aminoglycosides are a group of antibiotics used since the 1940s to primarily treat a broad spectrum of bacterial infections. The primary resistance mechanism against these antibiotics is enzymatic modification by aminoglycoside-modifying enzymes that are divided into acetyl-transferases, phosphotransferases, and nucleotidyltransferases. To overcome this
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Aminoglycosides are a group of antibiotics used since the 1940s to primarily treat a broad spectrum of bacterial infections. The primary resistance mechanism against these antibiotics is enzymatic modification by aminoglycoside-modifying enzymes that are divided into acetyl-transferases, phosphotransferases, and nucleotidyltransferases. To overcome this problem, new semisynthetic aminoglycosides were developed in the 70s. The most widely used semisynthetic aminoglycoside is amikacin, which is refractory to most aminoglycoside modifying enzymes. Amikacin was synthesized by acylation with the l-(−)-γ-amino-α-hydroxybutyryl side chain at the C-1 amino group of the deoxystreptamine moiety of kanamycin A. The main amikacin resistance mechanism found in the clinics is acetylation by the aminoglycoside 6′-N-acetyltransferase type Ib [AAC(6′)-Ib], an enzyme coded for by a gene found in integrons, transposons, plasmids, and chromosomes of Gram-negative bacteria. Numerous efforts are focused on finding strategies to neutralize the action of AAC(6′)-Ib and extend the useful life of amikacin. Small molecules as well as complexes ionophore-Zn+2 or Cu+2 were found to inhibit the acetylation reaction and induced phenotypic conversion to susceptibility in bacteria harboring the aac(6′)-Ib gene. A new semisynthetic aminoglycoside, plazomicin, is in advance stage of development and will contribute to renewed interest in this kind of antibiotics. Full article
(This article belongs to the Special Issue Recent Development on the New Applications of Aminoglycosides)
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Open AccessArticle Diarylheptanoid Glycosides of Morella salicifolia Bark
Molecules 2017, 22(12), 2266; https://doi.org/10.3390/molecules22122266
Received: 26 October 2017 / Revised: 2 December 2017 / Accepted: 4 December 2017 / Published: 19 December 2017
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Abstract
A methanolic extract of Morella salicifolia bark was fractionated by various chromatographic techniques yielding six previously unknown cyclic diarylheptanoids, namely, 7-hydroxymyricanol 5-O-β-d-glucopyranoside (1), juglanin B 3-O-β-d-glucopyranoside (2), 16-hydroxyjuglanin B 17-O
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A methanolic extract of Morella salicifolia bark was fractionated by various chromatographic techniques yielding six previously unknown cyclic diarylheptanoids, namely, 7-hydroxymyricanol 5-O-β-d-glucopyranoside (1), juglanin B 3-O-β-d-glucopyranoside (2), 16-hydroxyjuglanin B 17-O-β-d-glucopyranoside (3), myricanone 5-O-β-d-gluco-pranosyl-(1→6)-β-d-glucopyranoside (4), neomyricanone 5-O-β-d-glucopranosyl-(1→6)-β-d-glucopyranoside (5), and myricanone 17-O-α-l-arabino-furanosyl-(1→6)-β-d-glucopyranoside (6), respectively, together with 10 known cyclic diarylheptanoids. The structural diversity of the diarylheptanoid pattern in M. salicifolia resulted from varying glycosidation at C-3, C-5, and C-17 as well as from substitution at C-11 with hydroxy, carbonyl or sulfate groups, respectively. Structure elucidation of the isolated compounds was achieved on the basis of one- and two-dimensional nuclear magnetic resonance (NMR) as well as high-resolution electrospray ionisation mass spectrometry (HR-ESI-MS) analyses. The absolute configuration of the glycosides was confirmed after hydrolysis and synthesis of O-(S)-methyl butyrated (SMB) sugar derivatives by comparison of their 1H-NMR data with those of reference sugars. Additionally, absolute configuration of diarylheptanoid aglycones at C-11 was determined by electronic circular dichroism (ECD) spectra simulation and comparison with experimental CD spectra after hydrolysis. Full article
(This article belongs to the Section Natural Products Chemistry)
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Open AccessArticle Domain IV of Annexin A5 Is Critical for Binding Calcium and Guarantees Its Maximum Binding to the Phosphatidylserine Membrane
Molecules 2017, 22(12), 2256; https://doi.org/10.3390/molecules22122256
Received: 21 November 2017 / Revised: 8 December 2017 / Accepted: 14 December 2017 / Published: 19 December 2017
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Abstract
Background: Although domain IV of annexin A5 (anxA5) may be less effective in binding phosphatidylserine (PS), the four domains together may guarantee the maximum binding of anxA5 to the PS membrane. Additionally, previous research has shown that annexin mutants lacking one or
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Background: Although domain IV of annexin A5 (anxA5) may be less effective in binding phosphatidylserine (PS), the four domains together may guarantee the maximum binding of anxA5 to the PS membrane. Additionally, previous research has shown that annexin mutants lacking one or more domain(s) have different biological activities compared to the wild-type. The present research mainly aims to study the role of domain IV in the crucial PS-binding function of anxA5. Methods: The domain IV-truncated anxA5 protein was constructed and purified. Isothermal titration calorimetry, flow cytometry and activated partial thromboplastin time were adopted to examine the function of domain IV in anxA5-PS binding directly or indirectly. Results: The domain IV-truncated form of anxA5 is impaired in binding PS liposome and apoptotic cells, and anticoagulation activity. The mutant cannot bind calcium, but binds PS only in the presence of calcium. Conclusions: Truncation of domain IV of anxA5 destroys its calcium-binding ability and impairs its PS-binding activity. Truncation of domain IV may induce conformation change of anxA5 or reduce the hydrophobic interactions between protein and membrane, which may explain the decrease of PS-binding affinity of the mutant. Full article
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Open AccessArticle Studies on the Anti-Oxidative Function of trans-Cinnamaldehyde-Included β-Cyclodextrin Complex
Molecules 2017, 22(12), 1868; https://doi.org/10.3390/molecules22121868
Received: 31 October 2017 / Revised: 4 December 2017 / Accepted: 16 December 2017 / Published: 19 December 2017
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Abstract
trans-Cinnamaldehyde (tCIN), an active compound found in cinnamon, is well known for its antioxidant, anticancer, and anti-inflammatory activities. The β-cyclodextrin (β-CD) oligomer has been used for a variety of applications in nanotechnology, including pharmaceutical and cosmetic applications. Here, we aimed
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trans-Cinnamaldehyde (tCIN), an active compound found in cinnamon, is well known for its antioxidant, anticancer, and anti-inflammatory activities. The β-cyclodextrin (β-CD) oligomer has been used for a variety of applications in nanotechnology, including pharmaceutical and cosmetic applications. Here, we aimed to evaluate the anti-inflammatory and antioxidant effects of tCIN self-included in β-CD complexes (CIs) in lipopolysaccharide (LPS)-treated murine RAW 264.7 macrophages. RAW 264.7 macrophages were treated with increasing concentrations of β-CD, tCIN, or CIs for different times. β-CD alone did not affect the production of nitric oxide (NO) or reactive oxygen species (ROS). However, both tCIN and CI significantly reduced NO and ROS production. Thus, CIs may have strong anti-inflammatory and antioxidant effects, similar to those of tCIN when used alone. Full article
(This article belongs to the Special Issue Extractable and Non-Extractable Antioxidants)
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Open AccessArticle Synthesis and Biocompatibility Studies of New Iminodiacetic Acid Derivatives
Molecules 2017, 22(12), 2265; https://doi.org/10.3390/molecules22122265
Received: 12 November 2017 / Revised: 6 December 2017 / Accepted: 12 December 2017 / Published: 18 December 2017
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Abstract
Background: Iminodiacetic acid (IDA) derivatives can be used as ligands to form complexes with technetium, with potential application as hepatobiliary diagnostic agents. The aim of this study was to synthesize five novel IDA derivatives and to compare their effects on plasma haemostasis with
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Background: Iminodiacetic acid (IDA) derivatives can be used as ligands to form complexes with technetium, with potential application as hepatobiliary diagnostic agents. The aim of this study was to synthesize five novel IDA derivatives and to compare their effects on plasma haemostasis with clinically approved ligands for technetium complexation. Methods: The influence of synthesized IDA derivatives on plasma haemostasis was evaluated spectrophotometrically by clot formation and lysis test (CL-test), coagulation assay, Prothrombin Time and Activated Partial Tromboplastin Time. The effects of the tested compounds on erythrocytes were assessed using haemolysis assays, microscopy and flow cytometry studies. Results: Despite their significant influence on the kinetic parameters of the process of clot formation and fibrinolysis, the tested ligands, at potential diagnostic concentrations, did not alter the overall potential of clot formation and lysis (CLAUC). At potential diagnostic concentrations (0.4 μmol/mL) all the tested compounds showed no adverse effects on the membranes of RBCs (Red Blood Cells). Conclusion: IDA derivatives with methoxy substituents in aromatic ring, exert multidirectional effects on plasma haemostasis and should be considered safe as their significant impacts were mostly observed at 4 μmol/mL, which is about 10-fold higher than the theoretical plasma concentrations of these compounds. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Four New Compounds Obtained from Cultured Cells of Artemisia annua
Molecules 2017, 22(12), 2264; https://doi.org/10.3390/molecules22122264
Received: 11 November 2017 / Revised: 6 December 2017 / Accepted: 15 December 2017 / Published: 18 December 2017
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Abstract
Four new compounds obtained from cultured cells of Artemisia annua were reported. Products were detected by HPLC-ELSD/GC-MS and isolated by chromatographic methods. The structures of four new compounds, namely 6-hydroxy arteannuin I (1), 1-hydroxy arteannuin I (2), 2-hydroxy arteannuin
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Four new compounds obtained from cultured cells of Artemisia annua were reported. Products were detected by HPLC-ELSD/GC-MS and isolated by chromatographic methods. The structures of four new compounds, namely 6-hydroxy arteannuin I (1), 1-hydroxy arteannuin I (2), 2-hydroxy arteannuin J (3), and 14-hydroxy arteannuin J (4), were elucidated using their physico-chemical properties by NMR and MS data analyses. The results from the spontaneous oxidative experiment indicated that the biosynthesis of the new compounds was enzyme-catalyzed. Interestingly, the enzymes in the cultured cells of A. annua showed the abilities of substrate-selective and region-selective hydroxylation of the sesquiterpene lactone. Furthermore, the artemisinin contents were increased by 50% and 80% compared to the control group after the addition of arteannuin I/J to the suspension-cultured cells of A. annua under light and dark culture conditions, respectively. Full article
(This article belongs to the Section Bioorganic Chemistry)
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Open AccessArticle Pathogenic Acanthamoeba castellanii Secretes the Extracellular Aminopeptidase M20/M25/M40 Family Protein to Target Cells for Phagocytosis by Disruption
Molecules 2017, 22(12), 2263; https://doi.org/10.3390/molecules22122263
Received: 23 November 2017 / Revised: 14 December 2017 / Accepted: 15 December 2017 / Published: 18 December 2017
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Abstract
Acanthamoeba is free-living protist pathogen capable of causing a blinding keratitis and granulomatous encephalitis. However, the mechanisms of Acanthamoeba pathogenesis are still not clear. Here, our results show that cells co-cultured with pathogenic Acanthamoeba would be spherical and floated, even without contacting the
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Acanthamoeba is free-living protist pathogen capable of causing a blinding keratitis and granulomatous encephalitis. However, the mechanisms of Acanthamoeba pathogenesis are still not clear. Here, our results show that cells co-cultured with pathogenic Acanthamoeba would be spherical and floated, even without contacting the protists. Then, the Acanthamoeba protists would contact and engulf these cells. In order to clarify the contact-independent pathogenesis mechanism in Acanthamoeba, we collected the Acanthamoeba-secreted proteins (Asp) to incubate with cells for identifying the extracellular virulent factors and investigating the cytotoxicity process. The Asps of pathogenic Acanthamoeba express protease activity to reactive Leu amino acid in ECM and induce cell-losing adhesion ability. The M20/M25/M40 superfamily aminopeptidase protein (ACA1_264610), an aminopeptidase be found in Asp, is upregulated after Acanthamoeba and C6 cell co-culturing for 6 h. Pre-treating the Asp with leucine aminopeptidase inhibitor and the specific antibodies of Acanthamoeba M20/M25/M40 superfamily aminopeptidase could reduce the cell damage during Asp and cell co-incubation. These results suggest an important functional role of the Acanthamoeba secreted extracellular aminopeptidases in the Acanthamoeba pathogenesis process. This study provides information regarding clinically pathogenic isolates to target specific molecules and design combined drugs. Full article
(This article belongs to the Special Issue Protein Modifications and Bioconjugation)
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Open AccessArticle A DNA Barcode-Based RPA Assay (BAR-RPA) for Rapid Identification of the Dry Root of Ficus hirta (Wuzhimaotao)
Molecules 2017, 22(12), 2261; https://doi.org/10.3390/molecules22122261
Received: 16 November 2017 / Revised: 14 December 2017 / Accepted: 15 December 2017 / Published: 18 December 2017
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Abstract
Background: Wuzhimaotao (the dry root of Ficus hirta) is used as both medicine and food ingredient by the locals in areas around Nanling Mountains of China. Due to its very similar external morphologies with Duanchangcao (the root of Gelsemium elegans, which
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Background: Wuzhimaotao (the dry root of Ficus hirta) is used as both medicine and food ingredient by the locals in areas around Nanling Mountains of China. Due to its very similar external morphologies with Duanchangcao (the root of Gelsemium elegans, which contains gelsemine that is extremely neurotoxic) and the associated growth of these two plants, incidents of food poisoning and even death frequently occur, resulting from the misuse of Duanchangcao as Wuzhimaotao. The aim of this study is to develop a fast, even, on-spot approach to identification of Wuzhimaotao. Methods: We used DNA barcode-based recombinase polymerase amplification (BAR-RPA) with species–specific primers targeting the internal transcribed spacer (ITS) region of the rDNA of F. hirta. BAR-RPA reaction time and temperature were optimized and the specificity and sensitivity of BAR-RPA species–specific primers were assessed. Results: This technique showed a high specificity and sensitivity to amplify the genomic DNA of F. hirta and allowed for rapid amplification (within 15 min) of the ITS region under a constant and mild temperature range of 37–42 °C without using thermocyclers. Conclusions: The BAR-RPA assay with a fast DNA extraction protocol provides a simple, energy-saving, and rapid method for identification of Wuzhimaotao in both laboratory and field settings. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle AetMYC1, the Candidate Gene Controlling the Red Coleoptile Trait in Aegilops tauschii Coss. Accession As77
Molecules 2017, 22(12), 2259; https://doi.org/10.3390/molecules22122259
Received: 21 November 2017 / Revised: 14 December 2017 / Accepted: 15 December 2017 / Published: 18 December 2017
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Abstract
The red coleoptile trait can help monocotyledonous plants withstand stresses, and key genes responsible for the trait have been isolated from Triticum aestivum, Triticum urartu, and Triticum monococcum, but no corresponding research has been reported for Aegilops tauschii. In
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The red coleoptile trait can help monocotyledonous plants withstand stresses, and key genes responsible for the trait have been isolated from Triticum aestivum, Triticum urartu, and Triticum monococcum, but no corresponding research has been reported for Aegilops tauschii. In this research, transcriptome analysis was performed to isolate the candidate gene controlling the white coleoptile trait in Ae. tauschii. There were 5348 upregulated, differentially-expressed genes (DEGs) and 4761 downregulated DEGs in red coleoptile vs. white coleoptile plants. Among these DEGs, 12 structural genes and two transcription factors involved in anthocyanin biosynthesis were identified. The majority of structural genes showed lower transcript abundance in the white coleoptile of accession ‘As77’ than in the red coleoptile of accession ‘As60’, which implied that transcription factors related to anthocyanin biosynthesis could be the candidate genes. The MYB and MYC transcription factors AetMYB7D and AetMYC1 were both isolated from Ae. tauschii accessions ‘As60’ and ‘As77’, and their transcript levels analyzed. The coding sequence and transcript level of AetMYB7D showed no difference between ‘As60’ and ‘As77’. AetMYC1p encoded a 567-amino acid polypeptide in ‘As60’ containing the entire characteristic domains, bHLH-MYC_N, HLH, and ACT-like, belonging to the gene family involved in regulating anthocyanin biosynthesis. AetMYC1w encoded a 436-amino acid polypeptide in ‘As77’ without the ACT-like domain because a single nucleotide mutation at 1310 bp caused premature termination. Transient expression of AetMYC1p induced anthocyanin biosynthesis in ‘As77’ with the co-expression of AetMYB7D, while AetMYC1w could not cause induced anthocyanin biosynthesis under the same circumstances. Moreover, the transcript abundance of AetMYC1w was lower than that of AetMYC1p. AetMYC1 appears to be the candidate gene controlling the white coleoptile trait in Ae. tauschii, which can be used for potential biotech applications, such as producing new synthetic hexaploid wheat lines with different coleoptile colors. Full article
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Open AccessArticle Structure Features and Anti-Gastric Ulcer Effects of Inulin-Type Fructan CP-A from the Roots of Codonopsis pilosula (Franch.) Nannf.
Molecules 2017, 22(12), 2258; https://doi.org/10.3390/molecules22122258
Received: 23 October 2017 / Revised: 5 December 2017 / Accepted: 12 December 2017 / Published: 18 December 2017
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Abstract
Radix Codonopsis has been used in traditional Chinese medicine for strengthening the immune system, improving poor gastrointestinal function, treating gastric ulcers and chronic gastritis and so on. In the present study, an inulin-type fructan CP-A was obtained from the roots of Codonopsis pilosula
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Radix Codonopsis has been used in traditional Chinese medicine for strengthening the immune system, improving poor gastrointestinal function, treating gastric ulcers and chronic gastritis and so on. In the present study, an inulin-type fructan CP-A was obtained from the roots of Codonopsis pilosula (Franch.) Nannf. and its structure was confirmed by MS and NMR as (2 → 1) linked-β-d-fructofuranose. The protective effects of CP-A against ethanol-induced acute gastric ulcer in rats were intensively investigated. A Lacy assay demonstrated that CP-A-treated group (50 mg/kg) showed the gastric damage level 1, which was similar to the positive control group, while the model group exhibited the gastric damage level 3. The Guth assay demonstrated that the mucosa ulcer index for CP-A groups at the doses of 50 mg/kg and 25 mg/kg significantly decreased compared with that in the model group (p < 0.05). Meanwhile, CP-A significantly increased the activities of SOD and GSH-Px, and decreased the contents of MDA and NO, and the activity of MPO in gastric tissue in a dose-dependent manner (p < 0.05). The present research reported for the first time that inulin-type fructan CP-A were likely the potential component in Radix Codonopsis for treatment of acute gastric ulcers. Full article
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Open AccessArticle Microemulsion and Sol-Gel Synthesized ZrO2-MgO Catalysts for the Liquid-Phase Dehydration of Xylose to Furfural
Molecules 2017, 22(12), 2257; https://doi.org/10.3390/molecules22122257
Received: 31 October 2017 / Revised: 4 December 2017 / Accepted: 12 December 2017 / Published: 18 December 2017
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Abstract
Two series of catalysts were prepared by sol-gel and microemulsion synthetic procedure (SG and ME, respectively). Each series includes both pure Mg and Zr solids as well as Mg-Zr mixed solids with 25%, 50% and 75% nominal Zr content. The whole set of
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Two series of catalysts were prepared by sol-gel and microemulsion synthetic procedure (SG and ME, respectively). Each series includes both pure Mg and Zr solids as well as Mg-Zr mixed solids with 25%, 50% and 75% nominal Zr content. The whole set of catalysts was characterized from thermal, structural and surface chemical points of view and subsequently applied to the liquid-phase xylose dehydration to furfural. Reactions were carried out in either a high-pressure autoclave or in an atmospheric pressure multi-reactor under a biphasic (organic/water) reaction mixture. Butan-2-ol and toluene were essayed as organic solvents. Catalysts prepared by microemulsion retained part of the surfactant used in the synthetic procedure, mainly associated with the Zr part of the solid. The MgZr-SG solid presented the highest surface acidity while the Mg3Zr-SG one exhibited the highest surface basicity among mixed systems. Xylose dehydration in the high-pressure system and with toluene/water solvent mixture led to the highest furfural yield. Moreover, the yield of furfural increases with the Zr content of the catalyst. Therefore, the catalysts constituted of pure ZrO2 (especially Zr-SG) are the most suitable to carry out the process under study although MgZr mixed solids could be also suitable for overall processes with additional reaction steps. Full article
(This article belongs to the Special Issue Meeting of the Spanish Catalysis Society (SECAT’17))
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Open AccessArticle Identification of the Sex-Biased Gene Expression and Putative Sex-Associated Genes in Eucommia ulmoides Oliver Using Comparative Transcriptome Analyses
Molecules 2017, 22(12), 2255; https://doi.org/10.3390/molecules22122255
Received: 27 October 2017 / Revised: 29 November 2017 / Accepted: 14 December 2017 / Published: 18 December 2017
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Abstract
Eucommia ulmoides is a model representative of the dioecious plants with sex differentiation at initiation. Nevertheless, the genetic mechanisms of sexual dimorphism and sex determination in E. ulmoides remain poorly understood. In this study de novo transcriptome sequencing on Illumina platform generated >45
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Eucommia ulmoides is a model representative of the dioecious plants with sex differentiation at initiation. Nevertheless, the genetic mechanisms of sexual dimorphism and sex determination in E. ulmoides remain poorly understood. In this study de novo transcriptome sequencing on Illumina platform generated >45 billion high-quality bases from fresh leaves of six male and female individuals of E. ulmoides. A total of 148,595 unigenes with an average length of 801 base-pairs (bp) were assembled. Through comparative transcriptome analyses, 116 differentially expressed genes (DEGs) between the males and the females were detected, including 73 male-biased genes and 43 female-biased genes. Of these DEGs, three female-biased genes were annotated to be related with the sexually dimorphic gutta content in E. ulmoides. One male-biased DEG was identified as putative MADS box gene APETALA3, a B class floral organ identity gene in the flowering plants. SNPs calling analyses further confirmed that the APETALA3-like gene was probably involved in the sex determination in E. ulmoides. Four other male-biased DEGs were potential sex-associated genes as well with segregated SNPs in accord with sex type. In addition, the SNPs density was 1.02 per kilobase (kb) in the expressed genes of E. ulmoides, implying a relatively high genetic diversity. Full article
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Open AccessArticle GPCR Modulation of Thieno[2,3-b]pyridine Anti-Proliferative Agents
Molecules 2017, 22(12), 2254; https://doi.org/10.3390/molecules22122254
Received: 30 November 2017 / Revised: 11 December 2017 / Accepted: 15 December 2017 / Published: 18 December 2017
Cited by 1 | PDF Full-text (6559 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A panel of docking scaffolds was developed for the known molecular targets of the anticancer agents, thieno[2,3-b]pyridines, in order to glean insight into their mechanism of action. The reported targets are the copper-trafficking antioxidant 1 protein, tyrosyl DNA phosphodiesterase 1, the
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A panel of docking scaffolds was developed for the known molecular targets of the anticancer agents, thieno[2,3-b]pyridines, in order to glean insight into their mechanism of action. The reported targets are the copper-trafficking antioxidant 1 protein, tyrosyl DNA phosphodiesterase 1, the colchicine binding site in tubulin, adenosine A2A receptor, and, finally, phospholipase C-δ1. According to the panel, the A2A receptor showed the strongest binding, inferring it to be the most plausible target, closely followed by tubulin. To investigate whether the thieno[2,3-b]pyridines modulate G protein-coupled receptors (GPCRs) other than A2A, a screen against 168 GPCRs was conducted. According to the results, ligand 1 modulates five receptors in the low µM region, four as an antagonist; CRL-RAMP3 (IC50—11.9 µM), NPSR1B (IC50—1.0 µM), PRLHR (IC50—9.3 µM), and CXCR4 (IC50—6.9 µM). Finally, one agonist, GPRR35, was found (EC50 of 7.5 µM). Molecular modelling showed good binding to all of the receptors investigated; however, none of these surpass the A2A receptor. Furthermore, the newly-identified receptors are relatively modestly expressed in the cancer cell lines most affected by the thieno[2,3-b]pyridines, making them less likely to be the main targets of the mechanism of action for this compound class. Nevertheless, new modulators against GPCRs are of an interest as potential hits for further drug development. Full article
(This article belongs to the Special Issue Hit Generation and Verification for Novel Lead Compounds)
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