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Molecules, Volume 24, Issue 6 (March-2 2019)

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Open AccessFeature PaperArticle Cytinus hypocistis (L.) L. subsp. macranthus Wettst.: Nutritional Characterization
Molecules 2019, 24(6), 1111; https://doi.org/10.3390/molecules24061111 (registering DOI)
Received: 14 March 2019 / Revised: 14 March 2019 / Accepted: 16 March 2019 / Published: 20 March 2019
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Abstract
The habit of eating wild plants in Europe is often associated with times of famine; an example of such is the nectar of Cytinus hypocistis (L.) L., a parasitic plant. To the authors’ best knowledge, there are no studies on its nutritional and [...] Read more.
The habit of eating wild plants in Europe is often associated with times of famine; an example of such is the nectar of Cytinus hypocistis (L.) L., a parasitic plant. To the authors’ best knowledge, there are no studies on its nutritional and chemical composition; thus, the whole C. hypocistis (L.) L. subsp. macranthus Wettst. plant (CH) and its nectar (NCH) were nutritionally and chemically characterized. The proximate composition of CH and NCH were very similar in terms of energy, ash, and carbohydrate content. Protein and fat were approximately 2-fold higher in NCH, and crude fiber was 4.6-fold higher in CH compared to NCH. Fructose, glucose, sucrose, and trehalose were the free sugars present in both samples. Oxalic, malic, and citric acids were the identified organic acids in both samples, with citric acid as the most abundant molecule. For both samples, polyunsaturated and saturated fatty acids (PUFA and SFA, respectively) predominate over monounsaturated fatty acids (MUFA) due to the significant contribution of linoleic and palmitic acids, respectively. However, unsaturated fatty acids (UFA) prevail over SFA in CH and NCH. Therefore, CH proved to be an excellent source of nutritional compounds, which supports its use during past periods of scarcity. Full article
(This article belongs to the collection Bioactive Compounds)
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Open AccessArticle Facile Assembling of Novel 2,3,6,7,9-pentaazabicyclo- [3.3.1]nona-3,7-diene Derivatives under Microwave and Ultrasound Platforms
Molecules 2019, 24(6), 1110; https://doi.org/10.3390/molecules24061110 (registering DOI)
Received: 25 February 2019 / Revised: 13 March 2019 / Accepted: 14 March 2019 / Published: 20 March 2019
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Abstract
Reactions of a series of 3-oxo-2-arylhydrazonopropanal derivatives with two molar ratio of ammonium acetate afforded a library of tetrasubstituted 2,3,6,7,9-pentaazabicyclo[3.3.1]nona- 3,7-diene derivatives in good to excellent isolated yields. The reaction was activated with triethylamine catalyst under three different heating modes: thermal, ultrasonic and [...] Read more.
Reactions of a series of 3-oxo-2-arylhydrazonopropanal derivatives with two molar ratio of ammonium acetate afforded a library of tetrasubstituted 2,3,6,7,9-pentaazabicyclo[3.3.1]nona- 3,7-diene derivatives in good to excellent isolated yields. The reaction was activated with triethylamine catalyst under three different heating modes: thermal, ultrasonic and microwave irradiating conditions in ethanol solvent. The structures of the isolated products were fully characterized by spectral and analytical data as well as X-ray single crystal of selected examples. Full article
(This article belongs to the collection Heterocyclic Compounds)
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Open AccessArticle Triterpene Acid and Phenolics from Ancient Apples of Friuli Venezia Giulia as Nutraceutical Ingredients: LC-MS Study and In Vitro Activities
Molecules 2019, 24(6), 1109; https://doi.org/10.3390/molecules24061109 (registering DOI)
Received: 18 February 2019 / Revised: 12 March 2019 / Accepted: 15 March 2019 / Published: 20 March 2019
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Abstract
Triterpene acid and phenolic constituents from nine ancient varieties of apple (Malus domestica) fruits cultivated in Fanna, Friuli Venezia Giulia region, northeast Italy, were analyzed and compared with four commercial apples (‘Golden Delicious’, ‘Red Delicious’, ‘Granny Smith’ and ‘Royal Gala’). Total [...] Read more.
Triterpene acid and phenolic constituents from nine ancient varieties of apple (Malus domestica) fruits cultivated in Fanna, Friuli Venezia Giulia region, northeast Italy, were analyzed and compared with four commercial apples (‘Golden Delicious’, ‘Red Delicious’, ‘Granny Smith’ and ‘Royal Gala’). Total phenolic and flavonoid contents were measured by spectrophotometric assays. The quali-quantitative fingerprint of secondary metabolites including triterpene acid was obtained by LC-DAD-(ESI)-MS and LC-(APCI)-MS, respectively. Based on the two LC-MS datasets, multivariate analysis was used to compare the composition of ancient fruit varieties with those of four commercial apples. Significant differences related mainly to the pattern of triterpene acids were found. Pomolic, euscaphyc, maslinic and ursolic acids are the most abundant triterpene in ancient varieties pulps and peels, while ursolic and oleanolic acids were prevalent in the commercial fruits. Also, the content of the phenolic compounds phloretin-2-O-xyloglucoside and quercetin-3-O-arabinoside was greater in ancient apple varieties. The antioxidant (radical scavenging, reducing power, metal chelating and phosphomolybdenum assays) and enzyme inhibitory effects (against cholinesterase, tyrosinase, amylase and glucosidase) of the samples were investigated in vitro. Antioxidant assays showed that the peels were more active than pulps. However, all the samples exhibited similar enzyme inhibitory effects. Ancient Friuli Venezia Giulia apple cultivars can be a source of chlorogenic acid and various triterpene acids, which are known for their potential anti-inflammatory activity and beneficial effects on lipid and glucose metabolism. Our results make these ancient varieties suitable for the development of new nutraceutical ingredients. Full article
(This article belongs to the Special Issue Biological Activities of Plant Secondary Metabolites)
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Open AccessArticle Design and Synthesis of Matrine Derivatives as Novel Anti-Pulmonary Fibrotic Agents via Repression of the TGFβ/Smad Pathway
Molecules 2019, 24(6), 1108; https://doi.org/10.3390/molecules24061108 (registering DOI)
Received: 28 February 2019 / Revised: 13 March 2019 / Accepted: 14 March 2019 / Published: 20 March 2019
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Abstract
A total of 18 matrine derivatives were designed, synthesized, and evaluated for their inhibitory effect against TGF-β1-induced total collagen accumulation in human fetal lung fibroblast MRC-5 cell lines. Among them, compound 3f displayed the most potent anti-fibrotic activity (IC50 = 3.3 ± [...] Read more.
A total of 18 matrine derivatives were designed, synthesized, and evaluated for their inhibitory effect against TGF-β1-induced total collagen accumulation in human fetal lung fibroblast MRC-5 cell lines. Among them, compound 3f displayed the most potent anti-fibrotic activity (IC50 = 3.3 ± 0.3 μM) which was 266-fold more potent than matrine. 3f significantly inhibited the fibroblast-to-myofibroblast transition and extracellular matrix production of MRC-5 cells. The TGF-β/small mothers against decapentaplegic homologs (Smad) signaling was also inhibited by 3f, as evidenced by inhibition of cytoplasm-to-nuclear translocation of Smad2/3 and suppression of TGF-β1-induced upregulation of TGF-β receptor type I (TGFβRI). Additionally, 3f exhibited potent inhibitory effects against TGF-β1-induced fibroblasts migration. These data suggested that 3f might be a potential agent for the treatment of idiopathic pulmonary fibrosis via repression of the TGFβ/Smad signaling pathway. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Pressure-Dependent Structural and Luminescence Properties of 1-(Pyren-1-yl)but-2-yn-1-one
Molecules 2019, 24(6), 1107; https://doi.org/10.3390/molecules24061107 (registering DOI)
Received: 22 February 2019 / Revised: 14 March 2019 / Accepted: 15 March 2019 / Published: 20 March 2019
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Abstract
The crystal structure of 1-(pyren-1-yl)but-2-yn-1-one (1a, a polynuclear aromatic hydrocarbon displaying enhanced luminescence in the solid state, has been re-determined at several pressures ranging from atmospheric up to 3 GPa using a Diamond Anvil Cell (DAC). These experiments were augmented [...] Read more.
The crystal structure of 1-(pyren-1-yl)but-2-yn-1-one ( 1 a , a polynuclear aromatic hydrocarbon displaying enhanced luminescence in the solid state, has been re-determined at several pressures ranging from atmospheric up to 3 GPa using a Diamond Anvil Cell (DAC). These experiments were augmented by periodic DFT calculations at pressures up to 4.4 GPa. UV-Vis fluorescence of 1 a at non-ambient pressures has also been investigated. The crystal structure consists of infinite π -stacks of anti-parallel 1 a molecules with discernible dimers, which may exemplify aggregates formed by pyrene derivatives in solution and thin films, and is predominantly stabilized by dispersion. The average inter-planar distance between individual molecules within π -stacks decreases with pressure in the investigated range. This results in piezochromic properties of 1 a : a red-shift of sample color, as well as a bathochromic shift of fluorescence with pressure (by ca. 100 nm at 3.5 GPa). Two-component fluorescence spectra support the hypothesis that at least two types of excimers are involved in the electronic excitation processes in crystalline 1 a . Full article
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Open AccessArticle Autofluorescence Imaging Reflects the Nuclear Enlargement of Tumor Cells as well as the Cell Proliferation Ability and Aberrant Status of the p53, Ki-67, and p16 Genes in Colon Neoplasms
Molecules 2019, 24(6), 1106; https://doi.org/10.3390/molecules24061106 (registering DOI)
Received: 10 January 2019 / Revised: 14 March 2019 / Accepted: 15 March 2019 / Published: 20 March 2019
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Abstract
Background: Autofluorescence imaging (AFI) is useful for diagnosing colon neoplasms, but what affects the AFI intensity remains unclear. This study investigated the association between AFI and the histological characteristics, aberrant methylation status, and aberrant expression in colon neoplasms. Methods: Fifty-three patients with colorectal [...] Read more.
Background: Autofluorescence imaging (AFI) is useful for diagnosing colon neoplasms, but what affects the AFI intensity remains unclear. This study investigated the association between AFI and the histological characteristics, aberrant methylation status, and aberrant expression in colon neoplasms. Methods: Fifty-three patients with colorectal neoplasms who underwent AFI were enrolled. The AFI intensity (F index) was compared with the pathological findings and gene alterations. The F index was calculated using an image analysis software program. The pathological findings were assessed by the tumor crypt density, cell densities, and N/C ratio. The aberrant methylation of p16, E-cadherin, Apc, Runx3, and hMLH1 genes was determined by a methylation-specific polymerase chain reaction. The aberrant expression of p53 and Ki-67 was evaluated by immunohistochemical staining. Results: An increased N/C ratio, the aberrant expression of p53, Ki-67, and the altered methylation of p16 went together with a lower F index. The other pathological findings and the methylation status showed no association with the F index. Conclusions: AFI reflects the nuclear enlargement of tumor cells, the cell proliferation ability, and the altered status of cell proliferation-related genes, indicating that AFI is a useful and practical method for predicting the dysplastic grade of tumor cells and cell proliferation. Full article
(This article belongs to the Special Issue Autofluorescence Spectroscopy and Imaging)
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Open AccessArticle The Antidepressant-like Effect of Flavonoids from Trigonella Foenum-Graecum Seeds in Chronic Restraint Stress Mice via Modulation of Monoamine Regulatory Pathways
Molecules 2019, 24(6), 1105; https://doi.org/10.3390/molecules24061105 (registering DOI)
Received: 27 February 2019 / Revised: 17 March 2019 / Accepted: 19 March 2019 / Published: 20 March 2019
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Abstract
Fenugreek (Trigonella Foenum-Graecum) seeds flavonoids (FSF) have diverse biological activities, while the antidepressant-like effect of FSF has been seldom explored. The aim of this study was to evaluate the antidepressant-like effect of FSF and to identify the potential molecular mechanisms. LC-MS/MS [...] Read more.
Fenugreek (Trigonella Foenum-Graecum) seeds flavonoids (FSF) have diverse biological activities, while the antidepressant-like effect of FSF has been seldom explored. The aim of this study was to evaluate the antidepressant-like effect of FSF and to identify the potential molecular mechanisms. LC-MS/MS was used for the determination of FSF. Chronic restraint stress (CRS) was used to establish the animal model of depression. Observation of exploratory behavior in the forced swimming test (FST), tail suspension test (TST) and sucrose preference test (SPT) indicated the stress level. The serum corticosterone (CORT) level was measured. The monoamine neurotransmitters (5-HT, NE and DA) and their metabolites, as well as monoamine oxidase A (MAO-A) enzyme activity in the prefrontal cortex, hippocampus and striatum, were evaluated. The protein expression levels of KLF11, SIRT1, MAO-A were also determined by western blot analysis. The results showed that FSF treatment significantly reversed the CRS-induced behavioral abnormalities, including reduced sucrose preference and increased immobility time. FSF administration markedly restored CRS induced changes in concentrations of serum corticosterone, prefrontal cortex neurotransmitters (NE, 5-HT and DA), hippocampus neurotransmitters (NE, 5-HT and DA) and striatum neurotransmitters (NE). FSF treatment exhibited significant inhibition of MAO-A activity in the prefrontal cortex and hippocampus. FSF also significantly down-regulated the KLF11, SIRT1 and MAO-A protein expression levels in the prefrontal cortex and hippocampus. These findings indicate that FSF could exhibit an antidepressant-like effect by down-regulating the KLF11/SIRT1-MAO-A pathways, inhibiting MAO-A expression and activity, as well as up-regulating monoamine neurotransmitters levels. Full article
(This article belongs to the collection Herbal Medicine Research)
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Open AccessArticle Anti-Oxidative and Anti-Aging Activities of Porcine By-Product Collagen Hydrolysates Produced by Commercial Proteases: Effect of Hydrolysis and Ultrafiltration
Molecules 2019, 24(6), 1104; https://doi.org/10.3390/molecules24061104 (registering DOI)
Received: 30 January 2019 / Revised: 19 March 2019 / Accepted: 19 March 2019 / Published: 20 March 2019
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Abstract
To investigate methods for improving the processing of porcine waste, porcine skin was hydrolyzed using different commercially available proteases (Alcalase, Flavorzyme, Neutrase, Bromeline, Protamex, and Papain) under several optimal conditions. Following enzymatic hydrolysis, the collagen hydrolysates (CHs) were fractionated by molecular weight (3 [...] Read more.
To investigate methods for improving the processing of porcine waste, porcine skin was hydrolyzed using different commercially available proteases (Alcalase, Flavorzyme, Neutrase, Bromeline, Protamex, and Papain) under several optimal conditions. Following enzymatic hydrolysis, the collagen hydrolysates (CHs) were fractionated by molecular weight (3 kDa) via membrane ultrafiltration. The CHs were analyzed for physical properties (pH, protein recovery, free amino group content, molecular weight distribution, and amino composition) as well as for functional properties (antioxidant activities and anti-aging activities). Among the CHs, CHs hydrolyzed by Alcalase (CH-Alcalase) exhibited the highest degree of hydrolysis compared to other CHs. Both “CH-Alcalase” and “CH-Alcalase < 3 kDa” fractions showed a considerably high antioxidant activity and collagenase inhibition activity. Therefore, resulting bioactives have potential for development as antioxidants and anti-aging ingredients in the food, cosmetics, and pharmaceuticals, from animal by-products. Full article
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Open AccessArticle Thermal Conductivity of Defective Graphene Oxide: A Molecular Dynamic Study
Molecules 2019, 24(6), 1103; https://doi.org/10.3390/molecules24061103 (registering DOI)
Received: 13 February 2019 / Revised: 11 March 2019 / Accepted: 12 March 2019 / Published: 20 March 2019
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Abstract
In this paper, the thermal properties of graphene oxide (GO) with vacancy defects were studied using a non-equilibrium molecular dynamics method. The results showed that the thermal conductivity of GO increases with the model length. A linear relationship of the inverse length and [...] Read more.
In this paper, the thermal properties of graphene oxide (GO) with vacancy defects were studied using a non-equilibrium molecular dynamics method. The results showed that the thermal conductivity of GO increases with the model length. A linear relationship of the inverse length and inverse thermal conductivity was observed. The thermal conductivity of GO decreased monotonically with an increase in the degree of oxidation. When the degree of oxidation was 10%, the thermal conductivity of GO decreased by ~90% and this was almost independent of chiral direction. The effect of vacancy defect on the thermal conductivity of GO was also considered. The size effect of thermal conductivity gradually decreases with increasing defect concentration. When the vacancy defect ratio was beyond 2%, the thermal conductivity did not show significant change with the degree of oxidation. The effect of vacancy defect on thermal conductivity is greater than that of oxide group concentration. Our results can provide effective guidance for the designed GO microstructures in thermal management and thermoelectric applications. Full article
(This article belongs to the Special Issue Materials Chemistry of Fullerenes, Graphenes, and Carbon Nanotubes)
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Open AccessArticle Neuroprotective Effects of Ginsenosides against Cerebral Ischemia
Molecules 2019, 24(6), 1102; https://doi.org/10.3390/molecules24061102 (registering DOI)
Received: 26 January 2019 / Revised: 7 March 2019 / Accepted: 9 March 2019 / Published: 20 March 2019
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Abstract
Ginseng has been used worldwide as traditional medicine for thousands of years, and ginsenosides have been proved to be the main active components for their various pharmacological activities. Based on their structures, ginsenosides can be divided into ginseng diol-type A and ginseng triol-type [...] Read more.
Ginseng has been used worldwide as traditional medicine for thousands of years, and ginsenosides have been proved to be the main active components for their various pharmacological activities. Based on their structures, ginsenosides can be divided into ginseng diol-type A and ginseng triol-type B with different pharmacological effects. In this study, six ginsenosides, namely ginsenoside Rb1, Rh2, Rg3, Rg5 as diol-type ginseng saponins, and Rg1 and Re as triol-type ginseng saponins, which were reported to be effective for ischemia-reperfusion (I/R) treatment, were chosen to compare their protective effects on cerebral I/R injury, and their mechanisms were studied by in vitro and in vivo experiments. It was found that all ginsenosides could reduce reactive oxygen species (ROS), inhibit apoptosis and increase mitochondrial membrane potential in cobalt chloride-induced (CoCl2-induced) PC12 cells injury model, and they could reduce cerebral infarction volume, brain neurological dysfunction of I/R rats in vivo. The results of immunohistochemistry and western blot showed that the expression of Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), silencing information regulator (SIRT1) and nuclear transcription factor P65 (NF-κB) in hippocampal CA1 region of some ginsenoside groups were also reduced. In general, the effect on cerebral ischemia of Rb1 and Rg3 was significantly improved compared with the control group, and was the strongest among all the ginsenosides. The effect on SIRT1 activation of ginsenoside Rb1 and the inhibition effect of TLR4/MyD88 protein expression of ginsenoside Rb1 and Rg3 were significantly stronger than that of other groups. The results indicated that ginsenoside Rg1, Rb1, Rh2, Rg3, Rg5 and Re were effective in protecting the brain against ischemic injury, and ginsenoside Rb1 and Rg3 have the strongest therapeutic activities in all the tested ginsenosides. Their neuroprotective mechanism is associated with TLR4/MyD88 and SIRT1 activation signaling pathways, and they can reduce cerebral ischemic injury by inhibiting NF-κB transcriptional activity and the expression of proinflammatory cytokines, including interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Chromatographic Analysis and Anti-Oxidative Property of Naoxinqing Tablet, a Proprietary Preparation of Diospyros Kaki Leaves
Molecules 2019, 24(6), 1101; https://doi.org/10.3390/molecules24061101 (registering DOI)
Received: 31 October 2018 / Revised: 8 March 2019 / Accepted: 11 March 2019 / Published: 20 March 2019
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Abstract
The Naoxinqing (NXQ) tablet is a standardised proprietary herbal product containing an extract of persimmon leaves (Diospyros kaki) for the management of cardio- and cerebrovascular diseases. Although previous reports suggested that the efficacy of NXQ is at least partly mediated by [...] Read more.
The Naoxinqing (NXQ) tablet is a standardised proprietary herbal product containing an extract of persimmon leaves (Diospyros kaki) for the management of cardio- and cerebrovascular diseases. Although previous reports suggested that the efficacy of NXQ is at least partly mediated by its anti-oxidative property, the anti-oxidative effect of the major components of NXQ has not been studied systematically. For quality control purposes, only analytical methods limited to 3 marker analytes have been reported, the extent to which the other components affect efficacy has not been explored. In this study, we developed an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC MS/MS) method for the identification of seven analytes (kaempferol-3-O-glucoside (astragalin), quercetin-3-O-galactoside (hypericin), quercetin-3-O-glucoside (isoquercitin), kaempferol, 3,4-dihydroxybenzoic acid (protocatechuic acid), and furan-2-carboxylic acid (pyromucic acid) and quercetin) in the NXQ. This is the first method reported and validated for the quantification of the seven major secondary metabolites in NXQ. The results for the quantified analytes were then compared in 15 different batches of NXQ. The variation observed in the seven components highlights the need to quantify key bioactive components to ensure product consistency. Radical scavenging activity and abundance was used to rank the analytes. The anti-oxidative effects of NXQ were examined using cultured human vascular endothelial cells (EA.hy926). Corrected 2,2-di(4-tert-octylphenyl)-1-picrylhydrazyl (DPPH) activity results revealed that quercetin and kaempferol have the strongest anti-oxidant capacity in the extract. Both quercetin and kaempferol significantly inhibited the hydrogen peroxide (H2O2)-induced EA.hy926 cell injury and intracellular reactive oxygen species (ROS) generation. In conclusion, we established and validated an UPLC-MS/MC method for the analysis of major bioactive components in the NXQ and demonstrated that its anti-oxidative property may play a critical role in cerebrovascular protection. Full article
(This article belongs to the Special Issue The Antioxidant Capacities of Natural Products 2019)
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Open AccessFeature PaperArticle Identification of Bis-Cyclic Guanidines as Antiplasmodial Compounds from Positional Scanning Mixture-Based Libraries
Molecules 2019, 24(6), 1100; https://doi.org/10.3390/molecules24061100 (registering DOI)
Received: 19 February 2019 / Revised: 5 March 2019 / Accepted: 13 March 2019 / Published: 20 March 2019
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Abstract
The screening of more than 30 million compounds derived from 81 small molecule libraries built on 81 distinct scaffolds identified pyrrolidine bis-cyclic guanidine library (TPI-1955) to be one of the most active and selective antiplasmodial libraries. The screening of the positional scanning library [...] Read more.
The screening of more than 30 million compounds derived from 81 small molecule libraries built on 81 distinct scaffolds identified pyrrolidine bis-cyclic guanidine library (TPI-1955) to be one of the most active and selective antiplasmodial libraries. The screening of the positional scanning library TPI-1955 arranged on four sets of sublibraries (26 + 26 + 26 + 40), totaling 120 samples for testing provided information about the most important groups of each variable position in the TPI-1955 library containing 738,192 unique compounds. The parallel synthesis of the individual compounds derived from the deconvolution of the positional scanning library led to the identification of active selective antiplasmodial pyrrolidine bis-cyclic guanidines. Full article
(This article belongs to the Special Issue Small Molecule Drug Design)
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Open AccessArticle Determination of Optical Purity of Lactic Acid-Based Chiral Liquid Crystals and Corresponding Building Blocks by Chiral High-Performance Liquid Chromatography and Supercritical Fluid Chromatography
Molecules 2019, 24(6), 1099; https://doi.org/10.3390/molecules24061099 (registering DOI)
Received: 30 January 2019 / Revised: 8 March 2019 / Accepted: 14 March 2019 / Published: 20 March 2019
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Abstract
Liquid crystals (LCs) are among the most prominent materials of the current information age, mainly due to their well-known application in liquid crystal displays (LCDs). Their unique electro-optical properties stem from their ability to form organised structures (mesophases) on the transition from solid [...] Read more.
Liquid crystals (LCs) are among the most prominent materials of the current information age, mainly due to their well-known application in liquid crystal displays (LCDs). Their unique electro-optical properties stem from their ability to form organised structures (mesophases) on the transition from solid state to isotropic liquid. Molecules of LCs in a mesophase still maintain the anisotropy of solid crystals, while simultaneously exhibiting the fluidity of liquids, which gives the system the ability to react immediately to external stimuli such as electric or magnetic fields, light, mechanical stress, pressure and, of course, temperature. For the proper function of LC-based devices, not only chemical, but also optical purity of materials is strongly desirable, since any impurity could be detrimental to the self-assembly of the molecules. Therefore, in this study we aimed to verify synthetic methods published in the literature, which are used nowadays to prepare chiral building blocks based on lactic acid, for their enantioselectivity. Moreover, we have focused on the development of an analytical chiral separation method for target liquid crystalline materials. Using a chiral polysaccharide-based column operated in liquid chromatography mode, we show that not all published methods of LC synthesis are enantioselective, which could lead to significant differences in the properties of the resulting materials. We show that high-performance liquid chromatography with UV detection and supercritical fluid chromatography with UV and mass spectrometry detection enable full control over the chemical and optical purity of the target LCs and the corresponding chiral building blocks. For the first time, we utilise supercritical fluid chromatography with mass detection for the direct chiral analysis of liquid crystalline materials and impurities formed during the synthesis. Full article
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Open AccessReview Computational Drug Design Applied to the Study of Metabotropic Glutamate Receptors
Molecules 2019, 24(6), 1098; https://doi.org/10.3390/molecules24061098 (registering DOI)
Received: 5 February 2019 / Revised: 15 March 2019 / Accepted: 18 March 2019 / Published: 20 March 2019
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Abstract
Metabotropic glutamate (mGlu) receptors are a family of eight GPCRs that are attractive drug discovery targets to modulate glutamate action and response. Here we review the application of computational methods to the study of this family of receptors. X-ray structures of the extracellular [...] Read more.
Metabotropic glutamate (mGlu) receptors are a family of eight GPCRs that are attractive drug discovery targets to modulate glutamate action and response. Here we review the application of computational methods to the study of this family of receptors. X-ray structures of the extracellular and 7-transmembrane domains have played an important role to enable structure-based modeling approaches, whilst we also discuss the successful application of ligand-based methods. We summarize the literature and highlight the areas where modeling and experiment have delivered important understanding for mGlu receptor drug discovery. Finally, we offer suggestions of future areas of opportunity for computational work. Full article
(This article belongs to the Special Issue Allosteric Modulator)
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Open AccessArticle Oil-in-Water Emulsions Stabilized by Ultrasonic Degraded Polysaccharide Complex
Molecules 2019, 24(6), 1097; https://doi.org/10.3390/molecules24061097 (registering DOI)
Received: 11 February 2019 / Revised: 15 March 2019 / Accepted: 15 March 2019 / Published: 20 March 2019
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Abstract
The effects of ultrasound on the molecular weight distribution and emulsifying properties of both xanthan gum (XG) and propylene glycol alginate (PGA) were investigated. The results showed that ultrasonic treatment at different intensities decreased the apparent viscosity and narrowed the molecular weight distribution. [...] Read more.
The effects of ultrasound on the molecular weight distribution and emulsifying properties of both xanthan gum (XG) and propylene glycol alginate (PGA) were investigated. The results showed that ultrasonic treatment at different intensities decreased the apparent viscosity and narrowed the molecular weight distribution. Higher intensity increased the effectivity of the sonochemical effect. Ultrasound degradation did not change the primary structure of the PGA-XG complex, and SEM analysis showed that the morphology of the original polysaccharide differed from that of the degraded polysaccharide fractions. The ultrasonic intensities and treatment times had a substantial influence on the stability of the polysaccharide-stabilized oil-in-water (O/W) emulsions. The O/W emulsion stabilized by the polysaccharide treated with 270 W ultrasound waves for 7 min led to the smallest average particle size (detected via fluorescence microscopy) and showed stability against aggregation in O/W emulsions. Full article
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Open AccessArticle A Comparative Study on the Effects of Different Parts of Panax ginseng on the Immune Activity of Cyclophosphamide-Induced Immunosuppressed Mice
Molecules 2019, 24(6), 1096; https://doi.org/10.3390/molecules24061096 (registering DOI)
Received: 22 February 2019 / Revised: 10 March 2019 / Accepted: 16 March 2019 / Published: 20 March 2019
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Abstract
The objective of the present study was to compare the effects of the immunological activity of various parts (root/stem/leaf/flower/seed) of five-year-old ginseng on the immune system of immunosuppressive mice. Immunosuppression was induced by cyclophosphamide (CTX) in the mouse model, whereas levamisole hydrochloride tablet [...] Read more.
The objective of the present study was to compare the effects of the immunological activity of various parts (root/stem/leaf/flower/seed) of five-year-old ginseng on the immune system of immunosuppressive mice. Immunosuppression was induced by cyclophosphamide (CTX) in the mouse model, whereas levamisole hydrochloride tablet (LTH) was used for the positive control group. We found that ginseng root (GRT), ginseng leaf (GLF), and ginseng flower (GFR) could relieve immunosuppression by increased viability of NK cells, enhanced immune organ index, improved cell-mediated immune response, increased content of CD4+ and ratio of CD4+/CD8+, and recovery of macrophage function, including carbon clearance, phagocytic rate, and phagocytic index, in immunodeficient mice. However, ginseng stem (GSM) and ginseng seed (GSD) could only enhance the thymus indices, carbon clearance, splenocyte proliferation, NK cell activities, and the level of IL-4 in immunosuppressed mice. In CTX-injected mice, GRT and GFR remarkably increased the protein expression of Nrf2, HO-1, NQO1, SOD1, SOD2, and CAT in the spleen. As expected, oral administration of GRT and GFR markedly enhanced the production of cytokines, such as IL-1β, IL-4, IL-6, IFN-γ, and TNF-α, compared with the CTX-induced immunosuppressed mice, and GRT and GFR did this relatively better than GSM, GLF, and GSD. This study provides a theoretical basis for further study on different parts of ginseng. Full article
(This article belongs to the Special Issue Herbal Medicines–Unraveling Their Molecular Mechanism)
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Open AccessArticle Defining Processing Times for Accelerator Produced 225Ac and Other Isotopes from Proton Irradiated Thorium
Molecules 2019, 24(6), 1095; https://doi.org/10.3390/molecules24061095 (registering DOI)
Received: 20 February 2019 / Revised: 11 March 2019 / Accepted: 18 March 2019 / Published: 20 March 2019
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Abstract
During the purification of radioisotopes, decay periods or time dependent purification steps may be required to achieve a certain level of radiopurity in the final product. Actinum-225 (Ac-225), Silver-111 (Ag-111), Astatine-211 (At-211), Ruthenium-105 (Ru-105), and Rhodium-105 (Rh-105) are produced in a high energy [...] Read more.
During the purification of radioisotopes, decay periods or time dependent purification steps may be required to achieve a certain level of radiopurity in the final product. Actinum-225 (Ac-225), Silver-111 (Ag-111), Astatine-211 (At-211), Ruthenium-105 (Ru-105), and Rhodium-105 (Rh-105) are produced in a high energy proton irradiated thorium target. Experimentally measured cross sections, along with MCNP6-generated cross sections, were used to determine the quantities of Ac-225, Ag-111, At-211, Ru-105, Rh-105, and other co-produced radioactive impurities produced in a proton irradiated thorium target at Brookhaven Linac Isotope Producer (BLIP). Ac-225 and Ag-111 can be produced with high radiopurity by the proton irradiation of a thorium target at BLIP. Full article
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Open AccessArticle Toll-Like Receptor-Mediated Recognition of Nucleic Acid Nanoparticles (NANPs) in Human Primary Blood Cells
Molecules 2019, 24(6), 1094; https://doi.org/10.3390/molecules24061094 (registering DOI)
Received: 27 February 2019 / Revised: 12 March 2019 / Accepted: 18 March 2019 / Published: 20 March 2019
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Abstract
Infusion reactions (IRs) create a translational hurdle for many novel therapeutics, including those utilizing nanotechnology. Nucleic acid nanoparticles (NANPs) are a novel class of therapeutics prepared by rational design of relatively short oligonucleotides to self-assemble into various programmable geometric shapes. While cytokine storm, [...] Read more.
Infusion reactions (IRs) create a translational hurdle for many novel therapeutics, including those utilizing nanotechnology. Nucleic acid nanoparticles (NANPs) are a novel class of therapeutics prepared by rational design of relatively short oligonucleotides to self-assemble into various programmable geometric shapes. While cytokine storm, a common type of IR, has halted clinical development of several therapeutic oligonucleotides, NANP technologies hold tremendous potential to bring these reactions under control by tuning the particle’s physicochemical properties to the desired type and magnitude of the immune response. Recently, we reported the very first comprehensive study of the structure–activity relationship between NANPs’ shape, size, composition, and their immunorecognition in human cells, and identified the phagolysosomal pathway as the major route for the NANPs’ uptake and subsequent immunostimulation. Here, we explore the molecular mechanism of NANPs’ recognition by primary immune cells, and particularly the contributing role of the Toll-like receptors. Our current study expands the understanding of the immune recognition of engineered nucleic acid-based therapeutics and contributes to the improvement of the nanomedicine safety profile. Full article
(This article belongs to the Special Issue Therapeutic Nucleic Acids: Past, Present, and Future)
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Open AccessArticle Biological Evaluation and Molecular Docking Studies of Dimethylpyridine Derivatives
Molecules 2019, 24(6), 1093; https://doi.org/10.3390/molecules24061093 (registering DOI)
Received: 11 February 2019 / Revised: 16 March 2019 / Accepted: 18 March 2019 / Published: 20 March 2019
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Abstract
Cyclooxygenase inhibitors as anti-inflammatory agents can be used in chemoprevention. Many in vitro and in vivo studies on human and animal models have explained the mechanisms of the chemopreventive effect of COX inhibitors such as: induction of apoptosis, inhibition of neoplasia, angiogenesis suppression, [...] Read more.
Cyclooxygenase inhibitors as anti-inflammatory agents can be used in chemoprevention. Many in vitro and in vivo studies on human and animal models have explained the mechanisms of the chemopreventive effect of COX inhibitors such as: induction of apoptosis, inhibition of neoplasia, angiogenesis suppression, induction of cell cycle inhibition and inhibition of the expression of peroxisome proliferator-activated receptors. Here, biological evaluation of twelve different Schiff base derivatives of N-(2-hydrazine-2-oxoethyl)-4,6-dimethyl-2-sulfanylpyridine- 3-carboxamide are presented. Their in vitro anti-COX-1/COX-2, antioxidant and anticancer activities were studied. The molecular docking study was performed in order to understand the binding interaction of compounds in the active site of cyclooxygenases. Compounds PS18 and PS33 showed a significant inhibitory activity on COX-1 at lower concentrations compared to meloxicam and piroxicam. The IC50 of COX-1 of these compounds was 57.3 µM for PS18 and 51.8 µM for PS33. Out of the tested compounds, the highest therapeutic index was demonstrated by PS18, PS19, PS33, PS40 and PS41. Lower molar concentrations of these compounds inhibit the growth of cancer cells while not inhibiting the healthy cells. Compounds PS18, PS19 and PS33 simultaneously demonstrated a statistically-significant inhibition of COX-1 or COX-2. This opens up the possibility of applying these compounds in the chemoprevention of cancer. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Biological Evaluation and Molecular Dynamics Simulation of Chalcone Derivatives as Epidermal Growth Factor-Tyrosine Kinase Inhibitors
Molecules 2019, 24(6), 1092; https://doi.org/10.3390/molecules24061092 (registering DOI)
Received: 21 December 2018 / Revised: 12 March 2019 / Accepted: 13 March 2019 / Published: 20 March 2019
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Abstract
Targeted cancer therapy has become a high potential cancer treatment. Epidermal growth factor receptor (EGFR), which plays an important role in cell signaling, enhanced cell survival and proliferation, has been suggested as molecular target for the development of novel cancer therapeutics. In this [...] Read more.
Targeted cancer therapy has become a high potential cancer treatment. Epidermal growth factor receptor (EGFR), which plays an important role in cell signaling, enhanced cell survival and proliferation, has been suggested as molecular target for the development of novel cancer therapeutics. In this study, a series of chalcone derivatives was screened by in vitro cytotoxicity against the wild type (A431 and A549) and mutant EGFR (H1975 and H1650) cancer cell lines, and, subsequently, tested for EGFR-tyrosine kinase (TK) inhibition. From the experimental screening, all chalcones seemed to be more active against the A431 than the A549 cell line, with chalcones 1c, 2a, 3e, 4e, and 4t showing a more than 50% inhibitory activity against the EGFR-TK activity and a high cytotoxicity with IC50 values of < 10 µM against A431 cells. Moreover, these five chalcones showed more potent on H1975 (T790M/L858R mutation) than H1650 (exon 19 deletion E746-A750) cell lines. Only three chalcones (1c, 2a and 3e) had an inhibitory activity against EGFR-TK with a relative inhibition percentage that was close to the approved drug, erlotinib. Molecular dynamics studies on their complexes with EGFR-TK domain in aqueous solution affirmed that they were well-occupied within the ATP binding site and strongly interacted with seven hydrophobic residues, including the important hinge region residue M793. From the above information, as well as ADMET (absorption, distribution, metabolism, excretion, and toxicity) properties, all three chalcones could serve as lead compounds for the development of EGFR-TK inhibitors. Full article
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Open AccessArticle CLE-10 from Carpesium abrotanoides L. Suppresses the Growth of Human Breast Cancer Cells (MDA-MB-231) In Vitro by Inducing Apoptosis and Pro-Death Autophagy Via the PI3K/Akt/mTOR Signaling Pathway
Molecules 2019, 24(6), 1091; https://doi.org/10.3390/molecules24061091 (registering DOI)
Received: 22 February 2019 / Revised: 15 March 2019 / Accepted: 16 March 2019 / Published: 20 March 2019
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Abstract
Background: The antitumor activity of CLE-10 (4-epi-isoinuviscolide), a sesquiterpene lactone compound, isolated from Carpesium abrotanoides L. has rarely been reported. The aim of this study is to investigate the antitumor activity of CLE-10 and give a greater explanation of its underlying mechanisms. Methods: [...] Read more.
Background: The antitumor activity of CLE-10 (4-epi-isoinuviscolide), a sesquiterpene lactone compound, isolated from Carpesium abrotanoides L. has rarely been reported. The aim of this study is to investigate the antitumor activity of CLE-10 and give a greater explanation of its underlying mechanisms. Methods: The cytotoxicity of CLE-10 was evaluated using MTT assay. Autophagy was detected by the formation of mRFP-GFP-LC3 fluorescence puncta and observed using transmission electron microscopy, while flow cytometry was employed to detect apoptosis. The protein expressions were detected through Western blotting. Results: CLE-10 induced pro-death autophagy and apoptosis in MDA-MB-231 cells by increasing the protein expression of LC3-II, p-ULK1, Bax, and Bad, as well as downregulating p-PI3K, p-Akt, p-mTOR, p62, LC3-I, Bcl-2, and Bcl-xl. CLE-10 that was pretreated with 3-methyladenine (3-MA) or chloroquine (CQ) weakened the upregulation of the protein expression of p-ULK1, or the downregulation of p62, p-mTOR, and decreased the level of cytotoxicity against MDA-MB-231 cells. Meanwhile, rapamycin enhanced the effect of CLE-10 on the expression of autophagy-related protein and its cytotoxicity, with the IC50 value of CLE-10 decreasing from 4.07 µM to 2.38 µM. Conclusion: CLE-10 induced pro-death autophagy and apoptosis in MDA-MB-231 cells by upregulating the protein expressions of LC3-II, p-ULK1, Bax, and Bad and downregulating p-PI3K, p-Akt, p-mTOR, p62, Bcl-2, and Bcl-xl. Full article
(This article belongs to the Special Issue Antitumoral Properties of Natural Products)
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Open AccessArticle Antioxidative and Cardioprotective Effects of Schisandra chinensis Bee Pollen Extract on Isoprenaline-Induced Myocardial Infarction in Rats
Molecules 2019, 24(6), 1090; https://doi.org/10.3390/molecules24061090 (registering DOI)
Received: 8 February 2019 / Revised: 13 March 2019 / Accepted: 18 March 2019 / Published: 20 March 2019
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Abstract
Oxidative stress plays an important role in the pathogenesis of myocardial infarction (MI). Schisandra chinensis bee pollen extract (SCBPE) possesses powerful antioxidant capacity. This study aimed to further explore the antioxidative and cardioprotective effects of SCBPE on acute MI induced by isoprenaline (ISO) [...] Read more.
Oxidative stress plays an important role in the pathogenesis of myocardial infarction (MI). Schisandra chinensis bee pollen extract (SCBPE) possesses powerful antioxidant capacity. This study aimed to further explore the antioxidative and cardioprotective effects of SCBPE on acute MI induced by isoprenaline (ISO) in rats. The rats were intragastrically administrated with SCBPE (600, 1200, or 1800 mg/kg/day) and Compound Danshen dropping pills (270 mg/kg/day) for 30 days, then subcutaneously injected with ISO (65 mg/kg/day) on the 29th and 30th day. Compared with the model group, pretreatment with middle and high doses of SCBPE significantly reduced serum aspartate transaminase, lactate dehydrogenase, and creatine kinase activities and increased myocardial superoxide dismutase, glutathione peroxidase, and catalase activities. The histopathologic aspects showed that pathological heart change was found in the model group and reduced to varying degrees in the SCBPE groups. Moreover, the protein expression of nuclear factor-erythroid 2-related factor 2 (Nrf-2), heme oxygenase-1 (HO-1), and Bcl2 in the heart increased in the SCBPE groups, while that of Bax decreased compared to the model group. Besides this, uridine was isolated from S. chinensis bee pollen for the first time. This study could provide a scientific basis for using Schisandra chinensis bee pollen as a functional food for the prevention of MI. Full article
(This article belongs to the Special Issue Bee Products: From Molecules to Human Health)
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Open AccessReview Recent Advances in Phenylboronic Acid-Based Gels with Potential for Self-Regulated Drug Delivery
Molecules 2019, 24(6), 1089; https://doi.org/10.3390/molecules24061089
Received: 2 February 2019 / Revised: 14 March 2019 / Accepted: 15 March 2019 / Published: 19 March 2019
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Abstract
Glucose-sensitive drug platforms are highly attractive in the field of self-regulated drug delivery. Drug carriers based on boronic acid (BA), especially phenylboronic acid (PBA), have been designed for glucose-sensitive self-regulated insulin delivery. The PBA-functionalized gels have attracted more interest in recent years. The [...] Read more.
Glucose-sensitive drug platforms are highly attractive in the field of self-regulated drug delivery. Drug carriers based on boronic acid (BA), especially phenylboronic acid (PBA), have been designed for glucose-sensitive self-regulated insulin delivery. The PBA-functionalized gels have attracted more interest in recent years. The cross-linked three-dimensional (3D) structure endows the glucose-sensitive gels with great physicochemical properties. The PBA-based platforms with cross-linked structures have found promising applications in self-regulated drug delivery systems. This article summarizes some recent attempts at the developments of PBA-mediated glucose-sensitive gels for self-regulated drug delivery. The PBA-based glucose-sensitive gels, including hydrogels, microgels, and nanogels, are expected to significantly promote the development of smart self-regulated drug delivery systems for diabetes therapy. Full article
(This article belongs to the Special Issue Smart and Functional Polymers)
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Open AccessArticle Light-Induced Control of the Spin Distribution on Cu–Dithiolene Complexes: A Correlated Ab Initio Study
Molecules 2019, 24(6), 1088; https://doi.org/10.3390/molecules24061088
Received: 24 February 2019 / Revised: 12 March 2019 / Accepted: 14 March 2019 / Published: 19 March 2019
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Abstract
Metal dithiolene complexes—M(dmit)2—are key building blocks for magnetic, conducting, and optical molecular materials, with singular electronic structures resulting from the mixing of the metal and dmit ligand orbitals. Their use in the design of magnetic and conducting materials is linked to [...] Read more.
Metal dithiolene complexes—M(dmit)2—are key building blocks for magnetic, conducting, and optical molecular materials, with singular electronic structures resulting from the mixing of the metal and dmit ligand orbitals. Their use in the design of magnetic and conducting materials is linked to the control of the unpaired electrons and their localized/delocalized nature. It has been recently found that UV–Vis light can control the spin distribution of some [Cu(dmit)2]−2 salts in a direct and reversible way. In this work, we study the optical response of these salts and the origin of the differences observed in the EPR spectra under UV–Vis irradiation by means of wave function-based quantum chemistry methods. The low-lying states of the complex have been characterized and the electronic transitions with a non-negligible oscillator strength have been identified. The population of the corresponding excited states promoted by the UV–Vis absorption produces significant changes in the spin distribution, and could explain the changes observed in the system upon illumination. The interaction between neighbor [Cu(dmit)2]−2 complexes is weakly ferromagnetic, consistent with the relative orientation of the magnetic orbitals and the crystal packing, but in disagreement with previous assignments. Our results put in evidence the complex electronic structure of the [Cu(dmit)2]−2 radical and the relevance of a multideterminantal approach for an adequate analysis of their properties. Full article
(This article belongs to the Special Issue Open-Shell Systems for Functional Materials)
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Open AccessArticle A C21-Steroidal Glycoside from Cynanchum atratum Attenuates Concanavalin A-Induced Liver Injury in Mice
Molecules 2019, 24(6), 1087; https://doi.org/10.3390/molecules24061087
Received: 22 February 2019 / Revised: 12 March 2019 / Accepted: 12 March 2019 / Published: 19 March 2019
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Abstract
Cynatratoside A (CyA) is a C21 Steroidal glycoside with pregnane skeleton isolated from the root of Cynanchum atratum Bunge (Asclepiadaceae). This study aimed to investigate the effects of CyA on concanavalin A (Con A)-induced autoimmune hepatitis (AIH) and the underlying mechanism. CyA [...] Read more.
Cynatratoside A (CyA) is a C21 Steroidal glycoside with pregnane skeleton isolated from the root of Cynanchum atratum Bunge (Asclepiadaceae). This study aimed to investigate the effects of CyA on concanavalin A (Con A)-induced autoimmune hepatitis (AIH) and the underlying mechanism. CyA was orally administered to mice at 10 and 40 mg/kg 8 h before and 1 h after Con A treatment. The effects of CyA on Con A-induced spleen and liver in mice were assessed via histopathological changes, T lymphocyte amounts and the expressions of IL-1β and ICAM-1. Con A-induced L-02 hepatocytes were used to evaluate whether CyA (0.1–10 μM) can directly protect hepatocytes from cytotoxicity and the possible mechanism. The results revealed that CyA treatment could significantly improve the histopathological changes of spleen and liver, reduce the proliferation of splenic T lymphocytes, and decrease the expressions of IL-1β and ICAM-1 in liver. The experiment in vitro showed that CyA inhibited Con A-induced hepatotoxicity in a concentration-dependent manner. CyA (10 μM) significantly increased/decreased the expression of Bcl-2/Bax and reduced the levels of cleaved caspases-9 and -3. Our study demonstrated for the first time that CyA has a significant protective effect on Con A-induced AIH by inhibiting the activation and adhesion of T lymphocytes and blocking hepatocyte apoptosis. Full article
(This article belongs to the Section Chemical Biology)
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Open AccessArticle Radicinin, a Fungal Phytotoxin as a Target-Specific Bioherbicide for Invasive Buffelgrass (Cenchrus ciliaris) Control
Molecules 2019, 24(6), 1086; https://doi.org/10.3390/molecules24061086
Received: 13 February 2019 / Revised: 13 March 2019 / Accepted: 14 March 2019 / Published: 19 March 2019
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The fungal pathogens Cochliobolus australiensis and Pyricularia grisea have recently been isolated from diseased leaves of buffelgrass (Cenchrus ciliaris) in its North American range, and their ability to produce phytotoxic metabolites that could potentially be used as natural herbicides against this [...] Read more.
The fungal pathogens Cochliobolus australiensis and Pyricularia grisea have recently been isolated from diseased leaves of buffelgrass (Cenchrus ciliaris) in its North American range, and their ability to produce phytotoxic metabolites that could potentially be used as natural herbicides against this invasive weed was investigated. Fourteen secondary metabolites obtained from in vitro cultures of these two pathogens were tested by leaf puncture assay on the host plant at different concentrations. Radicinin and (10S, 11S)-epi-pyriculol proved to be the most promising compounds. Thus, their phytotoxic activity was also evaluated on non-host indigenous plants. Radicinin demonstrated high target-specific toxicity on buffelgrass, low toxicity to native plants, and no teratogenic, sub-lethal, or lethal effects on zebrafish (Brachydanio rerio) embryos. It is now under consideration for the development of a target-specific bioherbicide to be used against buffelgrass in natural systems where synthetic herbicides cause excessive damage to native plants. Full article
(This article belongs to the Special Issue Natural Compound to Biocontrol Agrarian Pests)
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Open AccessArticle Antioxidant, Gastroprotective, Cytotoxic Activities and UHPLC PDA-Q Orbitrap Mass Spectrometry Identification of Metabolites in Baccharis grisebachii Decoction
Molecules 2019, 24(6), 1085; https://doi.org/10.3390/molecules24061085
Received: 23 January 2019 / Revised: 7 March 2019 / Accepted: 14 March 2019 / Published: 19 March 2019
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Abstract
The decoction of the local plant Baccharis grisebachii is used as a digestive, gastroprotective, external cicatrizing agent and antiseptic in Argentine. A lyophilized decoction (BLD) from the aerial parts of this plant was evaluated regarding its anti-ulcer, antioxidant and cytotoxic activities and the [...] Read more.
The decoction of the local plant Baccharis grisebachii is used as a digestive, gastroprotective, external cicatrizing agent and antiseptic in Argentine. A lyophilized decoction (BLD) from the aerial parts of this plant was evaluated regarding its anti-ulcer, antioxidant and cytotoxic activities and the bioactivities were supported by UHPLC-MS metabolome fingerprinting which revealed the presence of several small bioactive compounds. The antioxidant properties were evaluated by DPPH, TEAC, FRAP and lipoperoxidation inhibition in erythrocytes methods, and the antibacterial activity was evaluated according to the Clinical and Laboratory Standards Institute (CLSI) guidelines. The BLD showed a moderate free radical scavenging activity in the DPPH (EC50 = 106 µg/mL) and lipid peroxidation in erythrocytes assays (67%, at 250 µg/mL). However, the BLD had the highest gastroprotective effect at a dose of 750 mg/kg with a ninety-three percent inhibition of damage through a mechanism that involve NO and prostaglandins using the ethanol-induced gastric damage in a standard rat model. On the other hand, BLD does not induce cytotoxic changes on human tumor and no-tumor cell lines at the concentrations assayed. Regarding the metabolomic analysis, thirty-one compounds were detected and 30 identified based on UHPLC-OT-MS including twelve flavonoids, eleven cinnamic acid derivatives, one coumarin, one stilbene and two other different phenolic compounds. The results support that the medicinal decoction of Baccharis grisebachii is a valuable natural product with gastroprotective effects and with potential to improve human health that opens a pathway for the development of important phytomedicine products. Full article
(This article belongs to the Special Issue Biological Activities of Plant Secondary Metabolites)
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Open AccessArticle 2-Deoxyglucose-Modified Folate Derivative: Self-Assembling Nanoparticle Able to Load Cisplatin
Molecules 2019, 24(6), 1084; https://doi.org/10.3390/molecules24061084
Received: 28 February 2019 / Revised: 15 March 2019 / Accepted: 18 March 2019 / Published: 19 March 2019
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Folic acid has been widely introduced into nano-drug delivery systems to give nanoparticle-targeted characteristics. However, the poor water solubility of folic acid may hinder the exploitation of its ability to load antineoplastic drugs. In the present study, we designed a new folate derivative [...] Read more.
Folic acid has been widely introduced into nano-drug delivery systems to give nanoparticle-targeted characteristics. However, the poor water solubility of folic acid may hinder the exploitation of its ability to load antineoplastic drugs. In the present study, we designed a new folate derivative (FA-2-DG) synthesized from folic acid and 2-Deoxyglucose (2-DG). The aim of this study was to evaluate the self-assembly characteristics of FA-2-DG, and its ability of loading cisplatin. The critical micelle concentration was 7.94 × 10−6 mol L−1. Fourier transform infrared spectroscopy indicated that hydrogen bonding interaction is a main driving force for the self–assembly of FA-2-DG. The particle was stable in pure water or 0.5% bovine serum albumin dispersions. By forming a coordination bond, the particles assembled from FA-2-DG can load cisplatin. The loading efficiency was maximal when the molar ratio of FA-2-DG to cisplatin was 2:1. Full article
(This article belongs to the Special Issue Advanced Self-Assembled Nanostructures)
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Open AccessArticle Identification of the Tetrel Bonds between Halide Anions and Carbon Atom of Methyl Groups Using Electronic Criterion
Molecules 2019, 24(6), 1083; https://doi.org/10.3390/molecules24061083
Received: 26 February 2019 / Revised: 15 March 2019 / Accepted: 16 March 2019 / Published: 19 March 2019
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Abstract
The consideration of the disposition of minima of electron density and electrostatic potential along the line between non-covalently bound atoms in systems with Hal···CH3–Y (Hal = Cl, Br; Y = N, O) fragments allowed to prove that the [...] Read more.
The consideration of the disposition of minima of electron density and electrostatic potential along the line between non-covalently bound atoms in systems with Hal···CH3–Y (Hal = Cl, Br; Y = N, O) fragments allowed to prove that the carbon atom in methyl group serves as an electrophilic site provider. These interactions between halide anion and carbon in methyl group can be categorized as the typical tetrel bonds. Statistics of geometrical parameters for such tetrel bonds in CSD is analyzed. It is established that the binding energy in molecular complexes with tetrel bonds correlate with the potential acting on an electron in molecule (PAEM). The PAEM barriers for tetrel bonds show a similar behavior for both sets of complexes with Br and Cl electron donors. Full article
(This article belongs to the Special Issue Tetrel Bonds)
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Open AccessArticle Characterization and Antibacterial Activity of 7S and 11S Globulins Isolated from Cowpea Seed Protein
Molecules 2019, 24(6), 1082; https://doi.org/10.3390/molecules24061082
Received: 18 February 2019 / Revised: 15 March 2019 / Accepted: 16 March 2019 / Published: 19 March 2019
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Abstract
The present work was carried out to determine the characteristics and antibacterial activity of 7S and 11S globulins isolated from cowpea seed (Vigna unguiculata (L.) Walp.). The molecular mass of 7S globulin was demonstrated by SDS-PAGE bands to be of about 132, [...] Read more.
The present work was carried out to determine the characteristics and antibacterial activity of 7S and 11S globulins isolated from cowpea seed (Vigna unguiculata (L.) Walp.). The molecular mass of 7S globulin was demonstrated by SDS-PAGE bands to be of about 132, 129 and 95 kDa corresponding the α/, α and β subunits. The molecular mass of 11S globulin was demonstrated by SDS-PAGE bands to be existed between 28 and 52 kDa corresponding the basic and acidic subunits. The minimum inhibitory concentrations MICs of 7S and 11S globulins isolated from cowpea seed were determined against Gram positive bacteria viz: Listeria monocytogenes LMG 10470, Listeria ivanovii FLB 12, Staphylococcus aureus ATCC 25923 and Streptococcus pyogenes ATCC 19615, and Gram negative bacteria such as Klebsiella pneumonia ATCC 43816, Pseudomonas aeruginosa ATCC 26853, Escherichia coli ATCC 25922 and Salmonella ATCC 14028 using disc diffusion assay; they were showed to be in the range 10 to 200 µg/mL. Transmission electron microscope (TEM) examination of the protein-treated bacteria showed the antibacterial action of 11S globulin against S. typhimurium and P. aeruginosa was manifested by signs of cellular deformation, partial and complete lysis of cell components. Adding 11S globulin at both concentrations 50 and 100 µg/g to minced meat showed considerable decreases in bacterial counts of viable bacteria, psychrotrophs and coliforms compared to controls during 15 days storage at 4 °C, reflecting a promising perspective to use such globulin as a meat bio-preservative. Full article
(This article belongs to the Special Issue Molecules for Biotechnologies)
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