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Molecules, Volume 23, Issue 10 (October 2018)

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Open AccessCommunication Ultra-High-Performance Liquid Chromatography Tandem Mass Spectrometry Assay for Determination of Endogenous GHB and GHB-Glucuronide in Nails
Molecules 2018, 23(10), 2686; https://doi.org/10.3390/molecules23102686 (registering DOI)
Received: 29 September 2018 / Revised: 11 October 2018 / Accepted: 15 October 2018 / Published: 18 October 2018
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Abstract
Background: The short chain fatty acid gamma-hydroxybutyric acid (GHB) is a precursor, and the metabolite of gamma-aminobutyric acid is commonly used as an illegal recreational drug of abuse. Methods: An ultra-high-performance liquid chromatography tandem mass spectrometry was developed and validated for
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Background: The short chain fatty acid gamma-hydroxybutyric acid (GHB) is a precursor, and the metabolite of gamma-aminobutyric acid is commonly used as an illegal recreational drug of abuse. Methods: An ultra-high-performance liquid chromatography tandem mass spectrometry was developed and validated for endogenous GHB and its glucuronide in nails, to complement hair in forensic contexts for a retrospective detection of psychotropic drugs consumption. Results: GHB endogenous values for children and adolescents, adult females, and adult males in fingernails ranged from 0.3 to 3.0, 3.2, and 3.8 ng/mg, respectively, and toenails values ranged from 0.3 to 1.8, 2.0, and 2.4 ng/mg, respectively. In the three different groups, values of GHB in fingernails were statistically higher than those in toenails. GHB glucuronide could only be detected in finger nails with values ranging from 0.08 to 0.233, 0.252 and 0.243 in children and adolescents, adult females and adult males, respectively. Conclusions: The validated method was efficaciously applied to real finger and toe nails specimens from a population of males and females non GHB consumers. A preliminary cut-off of 5.0 ng/mg nail for endogenous GHB and 0.5 ng/mg for endogenous GHB-Gluc in the general population was proposed. Full article
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Open AccessArticle Theoretical Investigations on the Reactivity of Methylidyne Radical toward 2,3,7,8-Tetrachlorodibenzo-p-Dioxin: A DFT and Molecular Dynamics Study
Molecules 2018, 23(10), 2685; https://doi.org/10.3390/molecules23102685 (registering DOI)
Received: 17 September 2018 / Revised: 15 October 2018 / Accepted: 16 October 2018 / Published: 18 October 2018
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Abstract
To explore the potential reactivity of the methylidyne radical (CH) toward 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), the reaction mechanism between them has been systematically investigated employing the density functional theory (DFT) and ab initio molecular dynamics simulations. The relevant thermodynamic and kinetic parameters in
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To explore the potential reactivity of the methylidyne radical (CH) toward 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), the reaction mechanism between them has been systematically investigated employing the density functional theory (DFT) and ab initio molecular dynamics simulations. The relevant thermodynamic and kinetic parameters in the possible reaction pathways have been discussed as well as the IR spectra and hyperfine coupling constants (hfcc’s) of the major products. Different from the reaction of the CH radical with 2,3,7,8-tetrachlorodibenzofuran, CH radical can attack all the C-C bonds of TCDD to form an initial intermediate barrierlessly via the cycloaddition mechanism. After then, the introduced C-H bond can be further inserted into the C-C bond of TCDD, resulting in the formation of a seven-membered ring structure. The whole reactions are favorable thermodynamically and kinetically. Moreover, the major products have been verified by ab initio molecular dynamics simulations. The distinct IR spectra and hyperfine coupling constants of the major products can provide some help for their experimental detection and identification. In addition, the reactivity of the CH radical toward the F- and Br-substituted TCDDs has also been investigated. Hopefully, the present findings can provide new insights into the reactivity of the CH radical in the transformation of TCDD-like dioxins. Full article
(This article belongs to the Special Issue Theoretical Investigations of Reaction Mechanisms)
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Open AccessReview Cellulose Nanomaterials—Binding Properties and Applications: A Review
Molecules 2018, 23(10), 2684; https://doi.org/10.3390/molecules23102684 (registering DOI)
Received: 18 September 2018 / Revised: 3 October 2018 / Accepted: 13 October 2018 / Published: 18 October 2018
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Abstract
Cellulose nanomaterials (CNs) are of increasing interest due to their appealing inherent properties such as bio-degradability, high surface area, light weight, chirality and the ability to form effective hydrogen bonds across the cellulose chains or within other polymeric matrices. Extending CN self-assembly into
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Cellulose nanomaterials (CNs) are of increasing interest due to their appealing inherent properties such as bio-degradability, high surface area, light weight, chirality and the ability to form effective hydrogen bonds across the cellulose chains or within other polymeric matrices. Extending CN self-assembly into multiphase polymer structures has led to useful end-results in a wide spectrum of products and countless innovative applications, for example, as reinforcing agent, emulsion stabilizer, barrier membrane and binder. In the current contribution, after a brief description of salient nanocellulose chemical structure features, its types and production methods, we move to recent advances in CN utilization as an ecofriendly binder in several disparate areas, namely formaldehyde-free hybrid composites and wood-based panels, papermaking/coating processes, and energy storage devices, as well as their potential applications in biomedical fields as a cost-effective and tissue-friendly binder for cartilage regeneration, wound healing and dental repair. The prospects of a wide range of hybrid materials that may be produced via nanocellulose is introduced in light of the unique behavior of cellulose once in nano dimensions. Furthermore, we implement some principles of colloidal and interfacial science to discuss the critical role of cellulose binding in the aforesaid fields. Even though the CN facets covered in this study by no means encompass the great amount of literature available, they may be regarded as the basis for future developments in the binder applications of these highly desirable materials. Full article
(This article belongs to the Special Issue Emerging Trends in Nanocelluloses)
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Open AccessArticle Design of a New α-1-C-Alkyl-DAB Derivative Acting as a Pharmacological Chaperone for β-Glucocerebrosidase Using Ligand Docking and Molecular Dynamics Simulation
Molecules 2018, 23(10), 2683; https://doi.org/10.3390/molecules23102683 (registering DOI)
Received: 10 September 2018 / Revised: 11 October 2018 / Accepted: 18 October 2018 / Published: 18 October 2018
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Abstract
Some point mutations in β-glucocerebrosidase cause either improper folding or instability of this protein, resulting in Gaucher disease. Pharmacological chaperones bind to the mutant enzyme and stabilize this enzyme; thus, pharmacological chaperone therapy was proposed as a potential treatment for Gaucher disease. The
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Some point mutations in β-glucocerebrosidase cause either improper folding or instability of this protein, resulting in Gaucher disease. Pharmacological chaperones bind to the mutant enzyme and stabilize this enzyme; thus, pharmacological chaperone therapy was proposed as a potential treatment for Gaucher disease. The binding affinities of α-1-C-alkyl 1,4-dideoxy-1,4-imino-d-arabinitol (DAB) derivatives, which act as pharmacological chaperones for β-glucocerebrosidase, abruptly increased upon elongation of their alkyl chain. In this study, the primary causes of such an increase in binding affinity were analyzed using protein–ligand docking and molecular dynamics simulations. We found that the activity cliff between α-1-C-heptyl-DAB and α-1-C-octyl-DAB was due to the shape and size of the hydrophobic binding site accommodating the alkyl chains, and that the interaction with this hydrophobic site controlled the binding affinity of the ligands well. Furthermore, based on the aromatic/hydrophobic properties of the binding site, a 7-(tetralin-2-yl)-heptyl-DAB compound was designed and synthesized. This compound had significantly enhanced activity. The design strategy in consideration of aromatic interactions in the hydrophobic pocket was useful for generating effective pharmacological chaperones for the treatment of Gaucher disease. Full article
(This article belongs to the Special Issue Application of Computational Methods in Drug Design)
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Open AccessArticle Melt Viscoelastic Assessment of Poly(Lactic Acid) Composting: Influence of UV Ageing
Molecules 2018, 23(10), 2682; https://doi.org/10.3390/molecules23102682 (registering DOI)
Received: 13 September 2018 / Revised: 15 October 2018 / Accepted: 15 October 2018 / Published: 18 October 2018
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Abstract
This study is devoted to the degradation pathway (bio, photo degradation and photo/bio) of Poly(Lactic acid) PLA polymers by means of melt viscoelasticity. A comparison was made between three PLA polymers with different microstructures (L, D stereoisomers). Biodegradability was determined during composting by
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This study is devoted to the degradation pathway (bio, photo degradation and photo/bio) of Poly(Lactic acid) PLA polymers by means of melt viscoelasticity. A comparison was made between three PLA polymers with different microstructures (L, D stereoisomers). Biodegradability was determined during composting by burying the polymer films in compost at 58 °C. Melt viscoelasticity was used to assess the molecular evolution of the materials during the composting process. Viscoelastic data were plotted in the complex plane. We used this methodology to check the kinetics of the molecular weight decrease during the initial stages of the degradation, through the evolution of Newtonian viscosity. After a few days in compost, the Newtonian viscosity decreased sharply, meaning that macromolecular chain scissions began at the beginning of the experiments. However, a double molar mass distribution was also observed on Cole–Cole plots, indicating that there is also a chain recombination mechanism competing with the chain scission mechanism. PLA hydrolysis was observed by infra-red spectroscopy, where acid characteristic peaks appeared and became more intense during experiments, confirming hydrolytic activity during the first step of biodegradation. During UV ageing, polymer materials undergo a deep molecular evolution. After photo-degradation, lower viscosities were measured during biodegradation, but no significant differences in composting were found. Full article
(This article belongs to the Special Issue Advances in Biodegradable Polymers)
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Open AccessArticle Computational Study of Mechanism and Thermodynamics of Ni/IPr-Catalyzed Amidation of Esters
Molecules 2018, 23(10), 2681; https://doi.org/10.3390/molecules23102681 (registering DOI)
Received: 21 September 2018 / Revised: 12 October 2018 / Accepted: 12 October 2018 / Published: 18 October 2018
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Abstract
Nickel catalysis has shown remarkable potential in amide C–N bond activation and functionalization. Particularly for the transformation between ester and amide, nickel catalysis has realized both the forward (ester to amide) and reverse (amide to ester) reactions, allowing a powerful approach for the
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Nickel catalysis has shown remarkable potential in amide C–N bond activation and functionalization. Particularly for the transformation between ester and amide, nickel catalysis has realized both the forward (ester to amide) and reverse (amide to ester) reactions, allowing a powerful approach for the ester and amide synthesis. Based on density functional theory (DFT) calculations, we explored the mechanism and thermodynamics of Ni/IPr-catalyzed amidation with both aromatic and aliphatic esters. The reaction follows the general cross-coupling mechanism, involving sequential oxidative addition, proton transfer, and reductive elimination. The calculations indicated the reversible nature of amidation, which highlights the importance of reaction thermodynamics in related reaction designs. To shed light on the control of thermodynamics, we also investigated the thermodynamic free energy changes of amidation with a series of esters and amides. Full article
(This article belongs to the Special Issue Amide Bond Activation)
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Open AccessArticle Enantioseparation, Stereochemical Assignment and Chiral Recognition Mechanism of Sulfoxide-Containing Drugs
Molecules 2018, 23(10), 2680; https://doi.org/10.3390/molecules23102680 (registering DOI)
Received: 15 September 2018 / Revised: 4 October 2018 / Accepted: 15 October 2018 / Published: 18 October 2018
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Abstract
The distinct pharmacodynamic and pharmacokinetic properties of enantiopure sulfoxide drugs have stimulated us to systematically investigate their chiral separation, stereochemical assignment, and chiral recognition mechanism. Herein, four clinically widely-used sulfoxide drugs were chosen and optically resolved on various chiral stationary phases (CSPs). Theoretical
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The distinct pharmacodynamic and pharmacokinetic properties of enantiopure sulfoxide drugs have stimulated us to systematically investigate their chiral separation, stereochemical assignment, and chiral recognition mechanism. Herein, four clinically widely-used sulfoxide drugs were chosen and optically resolved on various chiral stationary phases (CSPs). Theoretical simulations including electronic circular dichroism (ECD) calculation and molecular docking were adopted to assign the stereochemistry and reveal the underlying chiral recognition mechanism. Our results showed that the sequence of calculated mean binding energies between each pair of enantiomers and CSP matched exactly with experimentally observed enantiomeric elution order (EEO). It was also found that the length of hydrogen bond might contribute dominantly the interaction between two enantiomers and CSP. We hope our study could provide a fresh perspective to explore the stereochemistry and chiral recognition mechanism of chiral drugs. Full article
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Open AccessArticle A Near-Infrared Fluorescent Probe Based on a FRET Rhodamine Donor Linked to a Cyanine Acceptor for Sensitive Detection of Intracellular pH Alternations
Molecules 2018, 23(10), 2679; https://doi.org/10.3390/molecules23102679 (registering DOI)
Received: 18 September 2018 / Revised: 11 October 2018 / Accepted: 15 October 2018 / Published: 18 October 2018
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Abstract
A fluorescence resonance energy transfer (FRET)-based near-infrared fluorescent probe (B+) for double-checked sensitive detection of intracellular pH changes has been synthesized by binding a near-infrared rhodamine donor to a near-infrared cyanine acceptor through robust C-N bonds via a nucleophilic substitution
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A fluorescence resonance energy transfer (FRET)-based near-infrared fluorescent probe (B+) for double-checked sensitive detection of intracellular pH changes has been synthesized by binding a near-infrared rhodamine donor to a near-infrared cyanine acceptor through robust C-N bonds via a nucleophilic substitution reaction. To demonstrate the double-checked advantages of probe B+, a near-infrared probe (A) was also prepared by modification of a near-infrared rhodamine dye with ethylenediamine to produce a closed spirolactam residue. Under basic conditions, probe B+ shows only weak fluorescence from the cyanine acceptor while probe A displays nonfluorescence due to retention of the closed spirolactam form of the rhodamine moiety. Upon decrease in solution pH level, probe B+ exhibits a gradual fluorescence increase from rhodamine and cyanine constituents at 623 nm and 743 nm respectively, whereas probe A displays fluorescence increase at 623 nm on the rhodamine moiety as acidic conditions leads to the rupture of the probe spirolactam rings. Probes A and B+ have successfully been used to monitor intracellular pH alternations and possess pKa values of 5.15 and 7.80, respectively. Full article
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Open AccessArticle Preservation of Cichoric Acid Antioxidant Properties Loaded in Heat Treated Lactoferrin Nanoparticles
Molecules 2018, 23(10), 2678; https://doi.org/10.3390/molecules23102678 (registering DOI)
Received: 5 September 2018 / Revised: 15 October 2018 / Accepted: 17 October 2018 / Published: 18 October 2018
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Abstract
In the current research, a new cichoric acid (CA) encapsulation system was investigated. The optimal condition for the formation of lactoferrin-cichoric acid nanoparticles (LF-CA NPs) was determined by controlling the solution pH, the thermal treatment conditions, and the concentration of CA. Fluorescence indicated
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In the current research, a new cichoric acid (CA) encapsulation system was investigated. The optimal condition for the formation of lactoferrin-cichoric acid nanoparticles (LF-CA NPs) was determined by controlling the solution pH, the thermal treatment conditions, and the concentration of CA. Fluorescence indicated that the electrostatic force and the hydrophobic force were the main forces in the formation of LF-CA NPs. LF-CA NPs prepared under different conditions were spherical in shape with smaller particle sizes and good zeta potential demonstrating good colloidal stability. Especially, the prepared particle size of the LF-CA NPs at pH 7 and 95 °C was about 67.20 ± 1.86 nm. The circular dichroism (CD) and the Fourier transform infrared spectroscopy (FTIR) results showed that the combination of LF (lactoferrin) and CA affected the secondary structure of the LF. The differential scanning calorimetry (DSC) results indicated that the addition of CA increased the thermal stability of LF. In vitro antioxidant experiments confirmed the antioxidant capacity of LF-CA NPs was better than CA. CA was successfully encapsulated into LF NPs with high encapsulated efficiency (97.87–99.87%) by high performance liquid chromatography (HPLC). These results showed that LF could be used as the wall material of CA with excellent nature. Full article
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Open AccessArticle Differential Accumulation of Aroma Compounds in Normal Green and Albino-Induced Yellow Tea (Camellia sinensis) Leaves
Molecules 2018, 23(10), 2677; https://doi.org/10.3390/molecules23102677 (registering DOI)
Received: 26 September 2018 / Revised: 15 October 2018 / Accepted: 17 October 2018 / Published: 18 October 2018
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Abstract
Tea (Camellia sinensis) cultivars with green leaves are the most widely used for making tea. Recently, tea mutants with white or yellow young shoots have attracted increasing interest as raw materials for making “high-quality” tea products. Albino teas are generallycharacterized as
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Tea (Camellia sinensis) cultivars with green leaves are the most widely used for making tea. Recently, tea mutants with white or yellow young shoots have attracted increasing interest as raw materials for making “high-quality” tea products. Albino teas are generallycharacterized as having metabolites of relatively high amino acid content and lower catechin content. However, little is known about aroma compounds in albino tea leaves. Herein, we compared original normal leaves (green) and light-sensitive albino leaves (yellow) of cv. Yinghong No. 9. GC-MS was employed to analyze endogenous tea aroma compounds and related precursors. Quantitative real time PCR was used to measure expression levels of genes involved in biosyntheses of tea aromas.The total contents of most endogenous free tea aromas, including aroma fatty acid derivatives, aroma terpenes, and aroma phenylpropanoids/benzenoids, and their glycosidically bound aroma compounds, were lower in yellow leaves than in green leaves. The content of the key precursor geranyl diphosphate (GDP) and expression levels of key synthetic genes involved in the formation of linalool, a major aroma compound in cv. Yinghong No. 9, were investigated. Linalool content was lower in albino-induced yellow leaves, which was due to the lower GDP content compared with normal green leaves. Full article
(This article belongs to the collection Recent Advances in Flavors and Fragrances)
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Open AccessReview Use of Nutraceuticals in Angiogenesis-Dependent Disorders
Molecules 2018, 23(10), 2676; https://doi.org/10.3390/molecules23102676 (registering DOI)
Received: 5 September 2018 / Revised: 11 October 2018 / Accepted: 16 October 2018 / Published: 18 October 2018
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Abstract
The term of angiogenesis refers to the growth of new vessels from pre-existing capillaries. The phenomenon is necessary for physiological growth, repair and functioning of our organs. When occurring in a not regulated manner, it concurs to pathological conditions as tumors, eye diseases,
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The term of angiogenesis refers to the growth of new vessels from pre-existing capillaries. The phenomenon is necessary for physiological growth, repair and functioning of our organs. When occurring in a not regulated manner, it concurs to pathological conditions as tumors, eye diseases, chronic degenerative disorders. On the contrary insufficient neovascularization or endothelial disfunction accompanies ischemic and metabolic disorders. In both the cases an inflammatory and oxidative condition exists in supporting angiogenesis deregulation and endothelial dysfunction. The use of nutraceuticals with antioxidant and anti-inflammatory activities can be a therapeutic option to maintain an adequate vascularization and endothelial cell proper functioning or to blunt aberrant angiogenesis. A revision of the updated literature reports on nutraceuticals to guide endothelial cell wellness and to restore physiological tissue vascularization is the objective of this paper. The critical aspects as well as lacking data for human use will be explored from a pharmacological perspective. Full article
(This article belongs to the Special Issue Nutraceuticals and Their Medicinal Importance)
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Open AccessArticle Effects of Different Cultivation Parameters on the Production of Surfactin Variants by a Bacillus subtilis Strain
Molecules 2018, 23(10), 2675; https://doi.org/10.3390/molecules23102675 (registering DOI)
Received: 11 September 2018 / Revised: 16 October 2018 / Accepted: 17 October 2018 / Published: 18 October 2018
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Abstract
Surfactins are lipopeptide-type biosurfactants produced mainly by Bacillus species, consisting of a peptide loop of seven amino acids and a hydrophobic fatty acid chain (C12–C16). These molecules have been proven to exhibit various biological activities; thus, their therapeutic and
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Surfactins are lipopeptide-type biosurfactants produced mainly by Bacillus species, consisting of a peptide loop of seven amino acids and a hydrophobic fatty acid chain (C12–C16). These molecules have been proven to exhibit various biological activities; thus, their therapeutic and environmental applications are considered. Within the surfactin lipopeptide family, there is a wide spectrum of different homologues and isomers; to date, more than 30 variants have been described. Since the newest members of these lipopeptides were described recently, there is no information that is available on their characteristic features, e.g., the dependence of their production from different cultivation parameters. This study examined the effects of both the different carbon sources and various metal ions on the surfactin production of a selected B. subtilis strain. Among the applied carbon sources, fructose and xylose had the highest impacts on the ratio of the different variants, regarding both the peptide sequences and the lengths of the fatty acids. Furthermore, the application of metal ions Mn2+, Cu2+ and Ni2+ in the media completely changed the surfactin variant compositions of the fermenting broths leading to the appearance of methyl esterified surfactin forms, and resulted in the appearance of novel surfactin variants with fatty acid chains containing no more than 11 carbon atoms. Full article
(This article belongs to the Special Issue Cyclic Peptides)
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Open AccessArticle The Increase of Triterpene Saponin Production Induced by Trans-Anethole in Hairy Root Cultures of Panax quinquefolium
Molecules 2018, 23(10), 2674; https://doi.org/10.3390/molecules23102674
Received: 26 September 2018 / Revised: 15 October 2018 / Accepted: 17 October 2018 / Published: 17 October 2018
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Abstract
In vitro cultivation is an effective way to increase pharmaceutical production. To increase ginsenoside production in hairy root cultures of American ginseng, the present study uses trans-anethole as an elicitor. The content of nine triterpene saponins was determined: Rb1, Rb2, Rb3, Rc,
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In vitro cultivation is an effective way to increase pharmaceutical production. To increase ginsenoside production in hairy root cultures of American ginseng, the present study uses trans-anethole as an elicitor. The content of nine triterpene saponins was determined: Rb1, Rb2, Rb3, Rc, Rd, Rg1, Rg2, Re and Rf. Trans-anethole was found to stimulate saponin synthesis regardless of exposure time (24 and 72 h). Twenty-four hour exposure to 1 μmol trans-anethole in the culture medium resulted in the highest increase of total saponin content (twice that of untreated roots), and optimum accumulation of Rb-group saponins, with ginsenoside Rc dominating (8.45 mg g−1 d.w.). In contrast, the highest mean content of protopanaxatriol derivatives was obtained for 10 μmol trans-anethole. The Re metabolite predominated, reaching a concentration of 5.72 mg g−1 d.w.: a 3.9-fold increase over untreated roots. Elicitation with use of trans-anethole can therefore be an effective method of increasing ginsenoside production in shake flasks. Full article
(This article belongs to the collection Triterpenes and Triterpenoids)
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Open AccessReview Metal-Catalyzed Cross-Coupling Reactions on Azaindole Synthesis and Functionalization
Molecules 2018, 23(10), 2673; https://doi.org/10.3390/molecules23102673
Received: 28 September 2018 / Revised: 11 October 2018 / Accepted: 13 October 2018 / Published: 17 October 2018
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Abstract
Azaindoles are rare in nature but extremely attractive for drug discovery programs. Azaindoles can be obtained by diverse methods, including those involving metal-catalyzed reactions. This important core has been fascinating the scientific community due to their challenging synthesis and relevant bioactivity. This paper
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Azaindoles are rare in nature but extremely attractive for drug discovery programs. Azaindoles can be obtained by diverse methods, including those involving metal-catalyzed reactions. This important core has been fascinating the scientific community due to their challenging synthesis and relevant bioactivity. This paper highlights the diverse synthetic methodologies developed to date involving metal-catalyzed reaction to attain azaindoles and its functionalization. Full article
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Open AccessArticle Chromobacterium violaceum and Pseudomonas aeruginosa PAO1: Models for Evaluating Anti-Quorum Sensing Activity of Melaleuca alternifolia Essential Oil and Its Main Component Terpinen-4-ol
Molecules 2018, 23(10), 2672; https://doi.org/10.3390/molecules23102672
Received: 30 July 2018 / Revised: 8 October 2018 / Accepted: 11 October 2018 / Published: 17 October 2018
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Abstract
The problem of antibiotic resistance among pathogens encourages searching for novel active molecules. The aim of the research was to assay the anti-quorum sensing (anti-QS) and antibiofilm potential of Melaleuca alternifolia essential oil and its main constituent, terpinen-4-ol, to prevent the infections due
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The problem of antibiotic resistance among pathogens encourages searching for novel active molecules. The aim of the research was to assay the anti-quorum sensing (anti-QS) and antibiofilm potential of Melaleuca alternifolia essential oil and its main constituent, terpinen-4-ol, to prevent the infections due to methicillin-resistant Staphylococcus aureus strains as an alternate to antibiotics. The tea tree oil (TTO) was evaluated for its potential in inhibiting QS-dependent phenomena such as violacein production in Chromobacterium violaceum, swarming motility of Pseudomonas aeruginosa PAO1, and biofilm formation in MRSA strains on glass. The results showed that terpinen-4-ol was able to inhibit MRSA strain biofilm formation on the glass strips by 73.70%. TTO inhibited the violacein production at a mean inhibitory concentration (MIC) value of 0.048 mg/mL by 69.3%. At 100 µg/mL TTO and terpinen-4-ol exhibited inhibition in swarming motility of PAO1 by 33.33% and 25%, respectively. TTO revealed anti-QS and anti-biofilm activities at very low concentrations, but it could be further investigated for new molecules useful for the treatment of MRSA infections. Full article
(This article belongs to the collection Recent Advances in Flavors and Fragrances)
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Open AccessArticle Anti-Hyperuricemic Effect of 2-Hydroxy-4-methoxy-benzophenone-5-sulfonic Acid in Hyperuricemic Mice through XOD
Molecules 2018, 23(10), 2671; https://doi.org/10.3390/molecules23102671
Received: 30 August 2018 / Revised: 25 September 2018 / Accepted: 12 October 2018 / Published: 17 October 2018
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Abstract
Conventionally, benzophenone-type molecules are beneficial for alleviating the UV exposure of humans. More importantly, various compounds with this skeleton have demonstrated various biological activities. In this paper, we report the anti-hyperuricemic effect of the benzophenone compound 2-hydroxy-4-methoxybenzophenone-5-sulfonic acid (HMS). Preliminarily, its molecular docking
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Conventionally, benzophenone-type molecules are beneficial for alleviating the UV exposure of humans. More importantly, various compounds with this skeleton have demonstrated various biological activities. In this paper, we report the anti-hyperuricemic effect of the benzophenone compound 2-hydroxy-4-methoxybenzophenone-5-sulfonic acid (HMS). Preliminarily, its molecular docking score and xanthine oxidase (XOD) inhibition suggested a good anti-hyperuricemic effect. Then, its anti-hyperuricemic effect, primary mechanisms and general toxicity were examined on a hyperuricemic mouse model which was established using potassium oxonate and hypoxanthine together. HMS demonstrated a remarkable anti- hyperuricemic effect which was near to that of the control drugs, showing promising perspective. General toxicity was assessed and it showed no negative effects on body weight growth and kidney function. Moreover, anti-inflammatory action was observed for HMS via spleen and thymus changes. Its anti-hyperuricemic mechanisms may be ascribed to its inhibition of XOD and its up-regulation of organic anion transporter 1 (OAT1) and down-regulation of glucose transporter 9 (GLUT9). Full article
(This article belongs to the Special Issue QSAR and QSPR: Recent Developments and Applications)
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Open AccessArticle Fluorinated Tetraphosphonate Cavitands
Molecules 2018, 23(10), 2670; https://doi.org/10.3390/molecules23102670
Received: 28 September 2018 / Revised: 12 October 2018 / Accepted: 14 October 2018 / Published: 17 October 2018
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Abstract
Two synthetic protocols for the introduction of fluorine atoms into resorcinarene-based cavitands, at the lower and upper rim, respectively, are reported. Cavitand 1, bearing four fluorocarbon tails, and cavitand 2, which presents a fluorine atom on the para position of a
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Two synthetic protocols for the introduction of fluorine atoms into resorcinarene-based cavitands, at the lower and upper rim, respectively, are reported. Cavitand 1, bearing four fluorocarbon tails, and cavitand 2, which presents a fluorine atom on the para position of a diester phosphonate phenyl substituent, were synthesized and their complexation abilities toward the model guest sarcosine methyl ester hydrochloride were evaluated via NMR titration experiments. The effect of complexation on the 19F NMR resonance of the probe is evident only in the case of cavitand 2, where the inset of the cation-dipole and H-bonding interactions between the P=O bridges and the guest is reflected in a sizable downfield shift of the fluorine probe. Full article
(This article belongs to the Section Organic Chemistry)
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Open AccessArticle Failure of the Anti-Inflammatory Parasitic Worm Product ES-62 to Provide Protection in Mouse Models of Type I Diabetes, Multiple Sclerosis, and Inflammatory Bowel Disease
Molecules 2018, 23(10), 2669; https://doi.org/10.3390/molecules23102669
Received: 11 July 2018 / Revised: 24 September 2018 / Accepted: 10 October 2018 / Published: 17 October 2018
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Abstract
Parasitic helminths and their isolated secreted products show promise as novel treatments for allergic and autoimmune conditions in humans. Foremost amongst the secreted products is ES-62, a glycoprotein derived from Acanthocheilonema viteae, a filarial nematode parasite of gerbils, which is anti-inflammatory by
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Parasitic helminths and their isolated secreted products show promise as novel treatments for allergic and autoimmune conditions in humans. Foremost amongst the secreted products is ES-62, a glycoprotein derived from Acanthocheilonema viteae, a filarial nematode parasite of gerbils, which is anti-inflammatory by virtue of covalently-attached phosphorylcholine (PC) moieties. ES-62 has been found to protect against disease in mouse models of rheumatoid arthritis, systemic lupus erythematosus, and airway hyper-responsiveness. Furthermore, novel PC-based synthetic small molecule analogues (SMAs) of ES-62 have recently been demonstrated to show similar anti-inflammatory properties to the parent molecule. In spite of these successes, we now show that ES-62 and its SMAs are unable to provide protection in mouse models of certain autoimmune conditions where other helminth species or their secreted products can prevent disease development, namely type I diabetes, multiple sclerosis and inflammatory bowel disease. We speculate on the reasons underlying ES-62’s failures in these conditions and how the negative data generated may help us to further understand ES-62’s mechanism of action. Full article
(This article belongs to the Special Issue Immunomodulatory Compounds)
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Open AccessArticle Protective Effect of Bergenin against Cyclophosphamide-Induced Immunosuppression by Immunomodulatory Effect and Antioxidation in Balb/c Mice
Molecules 2018, 23(10), 2668; https://doi.org/10.3390/molecules23102668
Received: 1 September 2018 / Revised: 11 October 2018 / Accepted: 12 October 2018 / Published: 17 October 2018
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Abstract
In this study, the aim was to investigate the effect of bergenin on immune function and antioxidation in cyclophosphamide (Cy)-induced immunosuppressed mice. Firstly, we estimated its effect on immune organs. Histological analysis and indexes of immune organs showed that cyclophosphamide exhibited spleen and
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In this study, the aim was to investigate the effect of bergenin on immune function and antioxidation in cyclophosphamide (Cy)-induced immunosuppressed mice. Firstly, we estimated its effect on immune organs. Histological analysis and indexes of immune organs showed that cyclophosphamide exhibited spleen and thymus injury compared with the normal control, which was alleviated by bergenin. Secondly, bergenin also enhanced the humoral immune function through increasing the level of IgM and IgG in serum. Thirdly, bergenin also enhanced the cellular immune function. The results indicate that bergenin increased peritoneal macrophage functions, the proliferation of T and B lymphocytes, NK and CTL cell activities, and T (CD4+ and CD8+) lymphocyte subsets. Besides, bergenin also had the ability to modulate the Th1/Th2 balance. Moreover, bergenin prevented the Cy-induced decrease in numbers of peripheral RBC, WBC and platelets, providing supportive evidence for their anti-leukopenia activities. Finally, bergenin also reversed the Cy-induced decrease in the total antioxidant capacity including activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px). In conclusion, bergenin protected against Cy-induced adverse reactions by enhancing humoral and cellular immune functions and augmenting antioxidative activity and could be considered as a potential immunomodulatory agent. Full article
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Open AccessCommunication Increasing Antiradical Activity of Polyphenols from Lotus Seed Epicarp by Probiotic Bacteria Bioconversion
Molecules 2018, 23(10), 2667; https://doi.org/10.3390/molecules23102667
Received: 9 October 2018 / Revised: 15 October 2018 / Accepted: 15 October 2018 / Published: 17 October 2018
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Abstract
Probiotic bacteria is able to metabolize polyphenols and produce functional compounds. In this study, we investigated the ability of probiotic bacteria including Lactobacillus, bifidobacteria and Enterococcus strains to increase the antioxidant capacity of polyphenols from lotus seed epicarp (PLSE) at full ripening
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Probiotic bacteria is able to metabolize polyphenols and produce functional compounds. In this study, we investigated the ability of probiotic bacteria including Lactobacillus, bifidobacteria and Enterococcus strains to increase the antioxidant capacity of polyphenols from lotus seed epicarp (PLSE) at full ripening stage. The results showed that the six selected strains of probiotic bacteria grew well in De Man, Rogosa and Sharpe (MRS) broth with PLSE, and their resistant extent to PLSE varied from strain to strain. The metabolized PLSE was found to have good antioxidant properties on 3-ethylbenzothiazoline-6-sulfonic acid (ABTS+) and 1,1-diphenyl-2-picryl-hydrazyl (DPPH) radicals in vitro. Five polyphenol compounds—chlorogenic acid, caffeic acid, catechin, epicatechin and hyperoside—were suggested as the major bioactive metabolism for the antiradical activity of PLSE metabolized by Lactobacillus reuteri DSM20016, Enterococcus faecalis M74 and Bifidobacterium breve ATCC 15701. Moreover, L. reuteri DSM20016 and E. faecalis M74 were found to have a high PLSE bioconversion rate. Our results suggested that both L. reuteri DSM20016 and E. faecalis M74 might have excellent potential for the bioconversion of PLSE to increase its antiradical activity. Full article
(This article belongs to the Special Issue Bioactives from Bioprocessing: Sources and Production)
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Open AccessReview Synthesis of Multi-Substituted Pyrrole Derivatives Through [3+2] Cycloaddition with Tosylmethyl Isocyanides (TosMICs) and Electron-Deficient Compounds
Molecules 2018, 23(10), 2666; https://doi.org/10.3390/molecules23102666
Received: 13 September 2018 / Revised: 9 October 2018 / Accepted: 10 October 2018 / Published: 17 October 2018
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Abstract
Pyrrole and its polysubstituted derivatives are important five-membered heterocyclic compounds, which exist alone or as a core framework in many pharmaceutical and natural product structures, some of which have good biological activities. The Van Leusen [3+2] cycloaddition reaction based on tosylmethyl isocyanides (TosMICs)
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Pyrrole and its polysubstituted derivatives are important five-membered heterocyclic compounds, which exist alone or as a core framework in many pharmaceutical and natural product structures, some of which have good biological activities. The Van Leusen [3+2] cycloaddition reaction based on tosylmethyl isocyanides (TosMICs) and electron-deficient compounds as a substrate, which has been continuously developed due to its advantages such as operationally simple, easily available starting materials, and broadly range of substrates, is one of the most convenient methods to synthetize pyrrole heterocycles. In this review, we discuss the different types of two carbon synthons in the Van Leusen pyrrole reaction and give a summary of the progress of these synthesis methods in the past two decades. Full article
(This article belongs to the collection Heterocyclic Compounds)
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Open AccessFeature PaperArticle Evaluating Marine Cyanobacteria as a Source for CNS Receptor Ligands
Molecules 2018, 23(10), 2665; https://doi.org/10.3390/molecules23102665
Received: 12 September 2018 / Revised: 2 October 2018 / Accepted: 12 October 2018 / Published: 17 October 2018
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Abstract
Natural products have a long history as a source of psychoactive agents and pharmacological tools for understanding the brain and its circuitry. In the last two decades, marine cyanobacteria have become a standard source of natural product ligands with cytotoxic properties. The study
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Natural products have a long history as a source of psychoactive agents and pharmacological tools for understanding the brain and its circuitry. In the last two decades, marine cyanobacteria have become a standard source of natural product ligands with cytotoxic properties. The study of cyanobacterial metabolites as CNS modulatory agents has remained largely untapped, despite the need for new molecules to treat and understand CNS disorders. We have generated a library of 301 fractions from 37 field collected cyanobacterial samples and screened these fractions against a panel of CNS receptors using radiolabeled ligand competitive-binding assays. Herein we present an analysis of the screening data collected to date, which show that cyanobacteria are prolific producers of compounds which bind to important CNS receptors, including those for 5-HT, DA, monoamine transporters, adrenergic, sigma, and cannabinoid receptors. In addition to the analysis of our screening efforts, we will also present the isolation of five compounds from the same cyanobacterial collection to illustrate how pre-fractionation followed by radioligand screening can lead to rapid identification of selective CNS agents. The systematic screening of natural products sources, specifically filamentous marine cyanobacteria, will yield a number of lead compounds for further development as pharmacological tools and therapeutics. Full article
(This article belongs to the Special Issue Psychoactive Natural Products)
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Open AccessArticle Lignocellulosic Biomass as Source for Lignin-Based Environmentally Benign Antioxidants
Molecules 2018, 23(10), 2664; https://doi.org/10.3390/molecules23102664
Received: 14 September 2018 / Revised: 8 October 2018 / Accepted: 13 October 2018 / Published: 16 October 2018
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Abstract
Antioxidant activity is an essential aspect of oxygen-sensitive merchandise and goods, such as food and corresponding packaging, cosmetics, and biomedicine. Technical lignin has not yet been applied as a natural antioxidant, mainly due to the complex heterogeneous structure and polydispersity of lignin. This
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Antioxidant activity is an essential aspect of oxygen-sensitive merchandise and goods, such as food and corresponding packaging, cosmetics, and biomedicine. Technical lignin has not yet been applied as a natural antioxidant, mainly due to the complex heterogeneous structure and polydispersity of lignin. This report presents antioxidant capacity studies completed using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. The influence of purification on lignin structure and activity was investigated. The purification procedure showed that double-fold selective extraction is the most efficient (confirmed by ultraviolet-visible (UV/Vis), Fourier transform infrared (FTIR), heteronuclear single quantum coherence (HSQC) and 31P nuclear magnetic resonance spectroscopy, size exclusion chromatography, and X-ray diffraction), resulting in fractions of very narrow polydispersity (3.2–1.6), up to four distinct absorption bands in UV/Vis spectroscopy. Due to differential scanning calorimetry measurements, the glass transition temperature increased from 123 to 185 °C for the purest fraction. Antioxidant capacity is discussed regarding the biomass source, pulping process, and degree of purification. Lignin obtained from industrial black liquor are compared with beech wood samples: antioxidant activity (DPPH inhibition) of kraft lignin fractions were 62–68%, whereas beech and spruce/pine-mixed lignin showed values of 42% and 64%, respectively. Total phenol content (TPC) of the isolated kraft lignin fractions varied between 26 and 35%, whereas beech and spruce/pine lignin were 33% and 34%, respectively. Storage decreased the TPC values but increased the DPPH inhibition. Full article
(This article belongs to the Special Issue Lignin for Energy, Chemicals and Materials)
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Open AccessArticle Design, Synthesis of N-phenethyl Cinnamide Derivatives and Their Biological Activities for the Treatment of Alzheimer’s Disease: Antioxidant, Beta-amyloid Disaggregating and Rescue Effects on Memory Loss
Molecules 2018, 23(10), 2663; https://doi.org/10.3390/molecules23102663
Received: 1 September 2018 / Revised: 3 October 2018 / Accepted: 10 October 2018 / Published: 16 October 2018
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Abstract
Gx-50 is a bioactive compound for the treatment of Alzheimer’s disease (AD) found in Sichuan pepper (Zanthoxylum bungeanum). In order to find a stronger anti-AD lead compound, 20 gx-50 (120) analogs have been designed and synthesized, and
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Gx-50 is a bioactive compound for the treatment of Alzheimer’s disease (AD) found in Sichuan pepper (Zanthoxylum bungeanum). In order to find a stronger anti-AD lead compound, 20 gx-50 (120) analogs have been designed and synthesized, and their molecular structures were determined based on nuclear magnetic resonance (NMR) and mass spectrometry (MS) analysis, as well as comparison with literature data. Compounds 120 were evaluated for their anti-AD potential by using DPPH radical scavenging assay for considering their anti-oxidant activity, thioflavin T (ThT) fluorescence assay for considering the inhibitory or disaggregate potency of Aβ, and transgenic Drosophila model assay for evaluating their rescue effect on memory loss. Finally, compound 13 was determined as a promising anti-AD candidate. Full article
(This article belongs to the Special Issue Molecules against Alzheimer II)
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Open AccessArticle Inhibition of a Snake Venom Metalloproteinase by the Flavonoid Myricetin
Molecules 2018, 23(10), 2662; https://doi.org/10.3390/molecules23102662
Received: 4 September 2018 / Revised: 22 September 2018 / Accepted: 25 September 2018 / Published: 16 October 2018
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Abstract
Most of the snakebite envenomations in Central and South America are caused by species belonging to Bothrops genus. Their venom is composed mainly by zinc-dependent metalloproteinases, responsible of the hemorrhage characteristic of these envenomations. The aim of this study was to determine the
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Most of the snakebite envenomations in Central and South America are caused by species belonging to Bothrops genus. Their venom is composed mainly by zinc-dependent metalloproteinases, responsible of the hemorrhage characteristic of these envenomations. The aim of this study was to determine the inhibitory ability of ten flavonoids on the in-vitro proteolytic activity of Bothrops atrox venom and on the hemorrhagic, edema-forming and myonecrotic activities of Batx-I, the most abundant metalloproteinase isolated from this venom. Myricetin was the most active compound, exhibiting an IC 50 value of 150 μ M and 1021 μ M for the inhibition of proteolytic and hemorrhagic activity, respectively. Independent injection experiments, with a concentration of 1600 μ M of myricetin administered locally, immediately after toxin injection, demonstrated a reduction of 28 ± 6 % in the hemorrhagic lesion. Additionally, myricetin at concentrations 800, 1200 and 1600 μ M promoted a reduction in plasma creatine kinase activity induced by Batx-I of 21 ± 2 % , 60 ± 5 % and 63 ± 2 % , respectively. Molecular dynamics simulations coupled with the adaptive biasing method suggest that myricetin can bind to the metalloproteinase active site via formation of hydrogen bonds between the hydroxyl groups 3’, 4’ and 5’ of the benzyl moiety and amino acid Glu143 of the metalloproteinase. The hydroxyl substitution pattern of myricetin appears to be essential for its inhibitory activity. Based on this evidence, myricetin constitutes a candidate for the development of inhibitors to reduce local tissue damage in snakebite envenomations. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessReview Chitosan-Based Nanomaterials for Drug Delivery
Molecules 2018, 23(10), 2661; https://doi.org/10.3390/molecules23102661
Received: 15 September 2018 / Revised: 8 October 2018 / Accepted: 11 October 2018 / Published: 16 October 2018
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Abstract
This review discusses different forms of nanomaterials generated from chitosan and its derivatives for controlled drug delivery. Nanomaterials are drug carriers with multiple features, including target delivery triggered by environmental, pH, thermal responses, enhanced biocompatibility, and the ability to cross the blood-brain barrier.
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This review discusses different forms of nanomaterials generated from chitosan and its derivatives for controlled drug delivery. Nanomaterials are drug carriers with multiple features, including target delivery triggered by environmental, pH, thermal responses, enhanced biocompatibility, and the ability to cross the blood-brain barrier. Chitosan (CS), a natural polysaccharide largely obtained from marine crustaceans, is a promising drug delivery vector for therapeutics and diagnostics, owing to its biocompatibility, biodegradability, low toxicity, and structural variability. This review describes various approaches to obtain novel CS derivatives, including their distinct advantages, as well as different forms of nanomaterials recently developed from CS. The advanced applications of CS-based nanomaterials are presented here in terms of their specific functions. Recent studies have proven that nanotechnology combined with CS and its derivatives could potentially circumvent obstacles in the transport of drugs thereby improving the drug efficacy. CS-based nanomaterials have been shown to be highly effective in targeted drug therapy. Full article
(This article belongs to the Special Issue Chitosan-Based Nanomaterials for Biomedical Applications)
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Open AccessArticle Simultaneous Separation and Purification of Five Polymethoxylated Flavones from “Dahongpao” Tangerine (Citrus tangerina Tanaka) Using Macroporous Adsorptive Resins Combined with Prep-HPLC
Molecules 2018, 23(10), 2660; https://doi.org/10.3390/molecules23102660
Received: 29 August 2018 / Revised: 26 September 2018 / Accepted: 11 October 2018 / Published: 16 October 2018
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Abstract
In this study, a preparative separation method was established to simultaneously isolate the polymethoxylated flavones (PMFs) from the peel of “Dahongpao” tangerine using macroporous adsorptive resins (MARs) combined with prep-HPLC. The total PMFs were enriched using MARs to remove most sugars, water-soluble pigments,
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In this study, a preparative separation method was established to simultaneously isolate the polymethoxylated flavones (PMFs) from the peel of “Dahongpao” tangerine using macroporous adsorptive resins (MARs) combined with prep-HPLC. The total PMFs were enriched using MARs to remove most sugars, water-soluble pigments, and flavanones, and the eluents obtained were analyzed by ultra-performance liquid chromatography (UPLC) to determine the PMF composition. The separation and purification of PMFs were carried out by using a mass spectrometry-guided prep-HPLC with a gradient elution of acetonitrile-water (v/v), simultaneously. The purity of these PMFs was determined by UPLC, and their chemical structures were confirmed by electrospray ionization mass spectrometry (ESI-MS-MS), ultraviolet (UV), and nuclear magnetic resonance (NMR). Using the present method, five PMFs, including 5,6,7,4’-tetramethoxyflavone (1), nobiletin (2), tangeretin (3), sinensetin (4), and 5-hydroxy-6,7,8,3’,4’-pentamethoxyflavone (5), can be purified simultaneously, and the purity of the compounds obtained were 95.3%, 99.7%, 99.5%, 98.9%, and 98.1%, respectively. The method reported here is simple, rapid, and efficient, and it can be used to separate PMFs from citrus fruit peels and, potentially, other plant materials. Full article
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Open AccessArticle Biochemical Characterization of the Rice Cinnamyl Alcohol Dehydrogenase Gene Family
Molecules 2018, 23(10), 2659; https://doi.org/10.3390/molecules23102659
Received: 24 August 2018 / Revised: 9 October 2018 / Accepted: 13 October 2018 / Published: 16 October 2018
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Abstract
Cinnamyl alcohol dehydrogenase (CAD) is involved in the final step of the phenylpropanod pathway, catalyzing the NADPH-dependent reduction of hydroxy-cinnamaldehydes into the corresponding alcohols. The rice genome contains twelve CAD and CAD-like genes, collectively called OsCADs. To elucidate the biochemical function of
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Cinnamyl alcohol dehydrogenase (CAD) is involved in the final step of the phenylpropanod pathway, catalyzing the NADPH-dependent reduction of hydroxy-cinnamaldehydes into the corresponding alcohols. The rice genome contains twelve CAD and CAD-like genes, collectively called OsCADs. To elucidate the biochemical function of the OsCADs, OsCAD1, 2, 6, and 7, which are highly expressed in rice, were cloned from rice tissues. The cloned OsCADs were heterologously expressed in Escherichia coli as His-tag fusion proteins. The activity assay of the recombinant OsCADs showed that OsCAD2, 6, and 7 have CAD activity toward hydroxycinnamaldehydes, but OsCAD1 has no detectable catalytic activity. The kinetic parameters of the enzyme reactions demonstrated that OsCAD2 has the highest catalytic activity among the examined enzymes. This result agrees well with the finding that the Zn binding and NADPH binding motifs and the residues constituting the substrate binding pocket in bona fide plant CADs were fully conserved in OsCAD2. Although they have large variations in the residue for the substrate binding pocket, OsCAD6 and 7 catalyzed the reduction of hydroxycinnamaldehydes with a similar efficiency. Alignment of amino acid sequences showed that OsCAD1 lacks the GxxxxP motif for NADPH binding and has mismatches in residues important in the reduction process, which could be responsible for the loss of catalytic activity. OsCAD2 belongs to CAD Class I with bona fide CADs from other plant species and is constitutively expressed throughout the developmental stages of rice, with preferential expression in actively lignifying tissues such as the root, stem, and panicle, suggesting that it is mainly involved in developmental lignification in rice. The expression of OsCAD2 was also induced by biotic and abiotic stresses such as Xanthomonas oryzae pv. oryzae (Xoo) infection and UV-irradiation, suggesting that it plays a role in the defense response of rice, in addition to a bona fide role in developmental lignification. OsCAD6 and 7 belong in CAD Class II. Their expression is relatively lower than that of OsCAD2 and is confined to certain tissues, such as the leaf sheath, stem, and panicle. The expression of OsCAD6 was stimulated by Xoo infection and UV-irradiation. Thus OsCAD6 appears to be an inducible OsCAD that is likely involved in the defense response of rice against biotic and abiotic stresses. Full article
(This article belongs to the Section Bioorganic Chemistry)
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Open AccessArticle 1,4-β-d-Glucomannan from Dendrobium officinale Activates NF-кB via TLR4 to Regulate the Immune Response
Molecules 2018, 23(10), 2658; https://doi.org/10.3390/molecules23102658
Received: 15 September 2018 / Revised: 12 October 2018 / Accepted: 14 October 2018 / Published: 16 October 2018
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Abstract
2,3-O-acetylated-1,4-β-d-glucomannan (DOP-1-1) is a polysaccharide isolated from the stem of Dendrobium officinale. DOP-1-1 has been demonstrated to have remarkable immunomodulatory properties, but little is known about the influence of its structural diversity on bioactivity (and even
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2,3-O-acetylated-1,4-β-d-glucomannan (DOP-1-1) is a polysaccharide isolated from the stem of Dendrobium officinale. DOP-1-1 has been demonstrated to have remarkable immunomodulatory properties, but little is known about the influence of its structural diversity on bioactivity (and even less about the exact mechanism underlying its immune responses). First, DOP-1-1 was stabilized at different temperatures and pH conditions based on differential scanning calorimetry and size exclusion-chromatography–high-performance liquid chromatography. Then, a detailed study on the effects of DOP-1-1 on a human leukemia monocytic cell line (THP-1) under normal conditions was undertaken. DOP-1-1 promoted the translocation of nuclear factor-kappa B (NF-κB) and degradation of IκB proteins. The expression of genes and proteins closely associated with the immune, survival and apoptotic functions of NF-κB were analyzed by quantitative real-time RT-PCR. Furthermore, CCL4 and IP10 were confirmed to be the novel targets of the immune response stimulated by DOP-1-1. The phosphorylation of NF-кB was inhibited by treatment with a toll-like receptor 4 (TLR4) antagonist (TAK-242) and myeloid differentiation factor 88 (MyD88) inhibitor (ST2825). These data suggested: (i) the O-acetylated glucomannan DOP-1-1 is present in the steady state in low-pH solutions; (ii) DOP-1-1 can induce an immune response through NF-кB mediated by a TLR4 signaling pathway; and (iii) CCL4 and IP10 could be the novel targets of the immune response stimulated by O-acetylated glucomannan. Full article
(This article belongs to the Special Issue Immunomodulatory Compounds)
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Open AccessArticle Anticancer and Anti-Inflammatory Activities of Some New Pyrazolo[3,4-b]pyrazines
Molecules 2018, 23(10), 2657; https://doi.org/10.3390/molecules23102657
Received: 8 August 2018 / Revised: 30 August 2018 / Accepted: 3 September 2018 / Published: 16 October 2018
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Abstract
New derivatives of pyrazolo[3,4-b]pyrazines and related heterocycles were synthesized using 5-amino-3-methyl-4-nitroso-1-phenyl-pyrazole (1) as a starting material. The 5-acetyl derivative 15 was shown to be a useful key intermediate for the synthesis of several derivatives of pyrazolopyrazines. Some of the
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New derivatives of pyrazolo[3,4-b]pyrazines and related heterocycles were synthesized using 5-amino-3-methyl-4-nitroso-1-phenyl-pyrazole (1) as a starting material. The 5-acetyl derivative 15 was shown to be a useful key intermediate for the synthesis of several derivatives of pyrazolopyrazines. Some of the prepared compounds were evaluated for their anti-inflammatory and anti-breast cancer MCF-7 cell line activities. SAR study showed that compounds 15 and 29 exhibited remarkable anti-inflammatory activity, where 15 showed the same activity as that of the reference drug indomethacin. On the other hand, compounds 25i, 25j showed very significant inhibitory activity (p < 0.001) against MCF-7 breast cancer cell line. Full article
(This article belongs to the Section Bioorganic Chemistry)
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