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Molecules, Volume 24, Issue 12 (June-2 2019)

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Open AccessArticle
Assessment of the Bulgarian Wastewater Treatment Plants’ Impact on the Receiving Water Bodies
Molecules 2019, 24(12), 2274; https://doi.org/10.3390/molecules24122274 (registering DOI)
Received: 15 May 2019 / Revised: 9 June 2019 / Accepted: 17 June 2019 / Published: 18 June 2019
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Abstract
Deterioration of water quality is a major problem world widely according to many international non-governmental organizations (NGO). As one of the European Union (EU) countries, Bulgaria is also obliged by EU legislation to maintain best practices in assessing surface water quality and the [...] Read more.
Deterioration of water quality is a major problem world widely according to many international non-governmental organizations (NGO). As one of the European Union (EU) countries, Bulgaria is also obliged by EU legislation to maintain best practices in assessing surface water quality and the efficiency of wastewater treatment processes. For these reasons studies were undertaken to utilize ecotoxicological (Microtox®, Phytotoxkit FTM, Daphtoxkit FTM), instrumental (to determine pH, electrical conductivity (EC), chemical oxygen demand, total suspended solids (TSS), total nitrogen (N) and phosphorus (P), chlorides, sulphates, Cr, Co, Cu, Cd, Ba, V, Mn, Fe, Ni, Zn, Se, Pb), as well as advanced chemometric methods (partial least squares–discriminant analysis (PLS-DA)) in data evaluation to comprehensively assess wastewater treatment plants' (WWTPs) effluents and surface waters quality around 21 major Bulgarian cities. The PLS-DA classification model for the physicochemical parameters gave excellent discrimination between WWTP effluents and surface waters with 93.65% correct predictions (with significant contribution of EC, TSS, P, N, Cl, Fe, Zn, and Se). The classification model based on ecotoxicological data identifies the plant test endpoints as having a greater impact on the classification model efficiency than bacterial, or crustaceans’ endpoints studied. Full article
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Open AccessArticle
Methanol Extract of Aerial Parts of Pavetta indica L. Enhances the Cytotoxic Effect of Doxorubicin and Induces Radiation Sensitization in MDA-MB-231 Triple-Negative Breast Cancer Cells
Molecules 2019, 24(12), 2273; https://doi.org/10.3390/molecules24122273 (registering DOI)
Received: 24 May 2019 / Revised: 13 June 2019 / Accepted: 18 June 2019 / Published: 18 June 2019
PDF Full-text (3656 KB) | Supplementary Files
Abstract
Pavetta indica L. is used in traditional medicine for the treatment of various diseases including hemorrhoids, headache, urinary conditions, ulcerated nose, and dropsy. However, no study has evaluated the anticancer effect of P. indica L. In this study, we found that a methanol [...] Read more.
Pavetta indica L. is used in traditional medicine for the treatment of various diseases including hemorrhoids, headache, urinary conditions, ulcerated nose, and dropsy. However, no study has evaluated the anticancer effect of P. indica L. In this study, we found that a methanol extract of the leaves and branches of P. indica L. (MEPI) caused cellcycle arrest at the sub-G1 phase and induced apoptosis, as indicated by the activation of caspase-8, -3, -7, and c-PARP. Western blotting revealed that MEPI significantly reduced the levels of markers of the epithelial-mesenchymal transition, such as Vimentin, Snail, Slug, and matrix metallopeptidase 9. Notably, the expression of multidrug resistance-associated protein 1 in triple negative breast cancer (TNBC) was significantly decreased by MEPI. Moreover, the co-treatment with MEPI and doxorubicin resulted in a synergistic reduction in cell viability. MEPI also induced radiation sensitization of TNBC cells. Gas chromatography-mass spectrometry analysis revealed that 5,6-dehydrokawain (DK) is the major constituent of MEPI. Interestingly, DK exerted significant anti-invasive and anti-metastatic effects. Our results provide a strong rationale for investigating the molecular mechanisms of action of MEPI in TNBC. Full article
Open AccessReview
Symphytum Species: A Comprehensive Review on Chemical Composition, Food Applications and Phytopharmacology
Molecules 2019, 24(12), 2272; https://doi.org/10.3390/molecules24122272 (registering DOI)
Received: 14 May 2019 / Revised: 5 June 2019 / Accepted: 11 June 2019 / Published: 18 June 2019
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Abstract
Symphytum species belongs to the Boraginaceae family and have been used for centuries for bone breakages, sprains and rheumatism, liver problems, gastritis, ulcers, skin problems, joint pain and contusions, wounds, gout, hematomas and thrombophlebitis. Considering the innumerable potentialities of the Symphytum species and [...] Read more.
Symphytum species belongs to the Boraginaceae family and have been used for centuries for bone breakages, sprains and rheumatism, liver problems, gastritis, ulcers, skin problems, joint pain and contusions, wounds, gout, hematomas and thrombophlebitis. Considering the innumerable potentialities of the Symphytum species and their widespread use in the world, it is extremely important to provide data compiling the available literature to identify the areas of intense research and the main gaps in order to design future studies. The present review aims at summarizing the main data on the therapeutic indications of the Symphytum species based on the current evidence, also emphasizing data on both the efficacy and adverse effects. The present review was carried out by consulting PubMed (Medline), Web of Science, Embase, Scopus, Cochrane Database, Science Direct and Google Scholar (as a search engine) databases to retrieve the most updated articles on this topic. All articles were carefully analyzed by the authors to assess their strengths and weaknesses, and to select the most useful ones for the purpose of review, prioritizing articles published from 1956 to 2018. The pharmacological effects of the Symphytum species are attributed to several chemical compounds, among them allantoin, phenolic compounds, glycopeptides, polysaccharides and some toxic pyrrolizidine alkaloids. Not less important to highlight are the risks associated with its use. In fact, there is increasing consumption of over-the-counter drugs, which when associated with conventional drugs can cause serious and even fatal adverse events. Although clinical trials sustain the folk topical application of Symphytum species in musculoskeletal and blunt injuries, with minor adverse effects, its antimicrobial potency was still poorly investigated. Further studies are needed to assess the antimicrobial spectrum of Symphytum species and to characterize the active molecules both in vitro and in vivo. Full article
Open AccessReview
Cinnoline Scaffold—A Molecular Heart of Medicinal Chemistry?
Molecules 2019, 24(12), 2271; https://doi.org/10.3390/molecules24122271 (registering DOI)
Received: 31 May 2019 / Revised: 14 June 2019 / Accepted: 16 June 2019 / Published: 18 June 2019
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Abstract
The cinnoline nucleus is a very important bicyclic heterocycle that is used as the structural subunit of many compounds with interesting pharmaceutical properties. Cinnoline derivatives exhibit broad spectrum of pharmacological activities such as antibacterial, antifungal, antimalarial, anti-inflammatory, analgesic, anxiolytic and antitumor activities. Some [...] Read more.
The cinnoline nucleus is a very important bicyclic heterocycle that is used as the structural subunit of many compounds with interesting pharmaceutical properties. Cinnoline derivatives exhibit broad spectrum of pharmacological activities such as antibacterial, antifungal, antimalarial, anti-inflammatory, analgesic, anxiolytic and antitumor activities. Some of them are under evaluation in clinical trials. In the present review, we have compiled studies focused on the biological properties of cinnoline derivatives conducted by many research groups worldwide between 2005 and 2019. Comprehensive and target oriented information clearly indicate that the development of cinnoline based molecules constitute a significant contribution to the identification of lead compounds with optimized pharmacodynamic and pharmacokinetic properties. Full article
(This article belongs to the Special Issue Heterocycles in Medicinal Chemistry)
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Open AccessArticle
Comprehensive Analysis of Secondary Metabolites in Usnea longissima (Lichenized Ascomycetes, Parmeliaceae) Using UPLC-ESI-QTOF-MS/MS and Pro-Apoptotic Activity of Barbatic Acid
Molecules 2019, 24(12), 2270; https://doi.org/10.3390/molecules24122270 (registering DOI)
Received: 2 May 2019 / Revised: 6 June 2019 / Accepted: 8 June 2019 / Published: 18 June 2019
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Abstract
Considering the importance of ultra-performance liquid chromatography-electrospray ionization-quadrupole time of flight-tandem mass spectrometry (UPLC-ESI-QTOF-MS/MS) hyphenated techniques for analysis of secondary metabolites from crude extracts, the present study was aimed at identification of secondary metabolites in acetone extract of the lichen Usnea longissima. [...] Read more.
Considering the importance of ultra-performance liquid chromatography-electrospray ionization-quadrupole time of flight-tandem mass spectrometry (UPLC-ESI-QTOF-MS/MS) hyphenated techniques for analysis of secondary metabolites from crude extracts, the present study was aimed at identification of secondary metabolites in acetone extract of the lichen Usnea longissima. From our study, 19 compounds were tentatively identified through comparison of exact molecular masses from their MS/MS spectra, mass fragmentation studies and comparison with literature data. In addition, potent cytotoxic activity of U. longissima extract prompted us to isolate four compounds, 18R-hydroxy-dihydroalloprotolichesterinic acid (19), neuropogolic acid (20), barbatic acid (21), and usnic acid (22) from this extract which were adequately identified through mass spectrometry and NMR spectroscopy. All four compounds displayed cytotoxic activity. Barbatic acid (21) manifested doxorubicin equivalent activity against A549 lung cancer cell line with IC50 of 1.78 µM and strong G0/G1 accumulation of cells. Poly ADP-ribose polymerase (PARP) cleavage confirmed that it induced cytotoxic activity via apoptosis. Finally, our work has discerned the depside, barbatic acid (21) from crude extract as a candidate anti-cancer molecule, which induces cell death by stepping up apoptosis. Full article
(This article belongs to the Special Issue Lichens: Chemistry, Ecological and Biological Activities II)
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Open AccessFeature PaperArticle
Generative Topographic Mapping of the Docking Conformational Space
Molecules 2019, 24(12), 2269; https://doi.org/10.3390/molecules24122269 (registering DOI)
Received: 20 May 2019 / Revised: 14 June 2019 / Accepted: 15 June 2019 / Published: 18 June 2019
PDF Full-text (3636 KB)
Abstract
Following previous efforts to render the Conformational Space (CS) of flexible compounds by Generative Topographic Mapping (GTM), this polyvalent mapping technique is here adapted to the docking problem. Contact fingerprints (CF) characterize ligands from the perspective of the binding site by monitoring protein [...] Read more.
Following previous efforts to render the Conformational Space (CS) of flexible compounds by Generative Topographic Mapping (GTM), this polyvalent mapping technique is here adapted to the docking problem. Contact fingerprints (CF) characterize ligands from the perspective of the binding site by monitoring protein atoms that are “touched” by those of the ligand. A “Contact” (CF) map was built by GTM-driven dimensionality reduction of the CF vector space. Alternatively, a “Hybrid” (Hy) map used a composite descriptor of CFs concatenated with ligand fragment descriptors. These maps indirectly represent the active site and integrate the binding information of multiple ligands. The concept is illustrated by a docking study into the ATP-binding site of CDK2, using the S4MPLE program to generate thousands of poses for each ligand. Both maps were challenged to (1) Discriminate native from non-native ligand poses, e.g., create RMSD-landscapes “colored” by the conformer ensemble of ligands of known binding modes in order to highlight “native” map zones (poses with RMSD to PDB structures < 2Å). Then, projection of poses of other ligands on such landscapes might serve to predict those falling in native zones as being well-docked. (2) Distinguish ligands–characterized by their ensemble of conformers–by their potency, e.g., testing the hypotheses whether zones privileged by potent binders are clearly separated from the ones preferred by decoys on the maps. Hybrid maps were better in both challenges and outperformed the classical energy and individual contact satisfaction scores in discriminating ligands by potency. Moreover, the intuitive visualization and analysis of docking CS may, as already mentioned, have several applications–from highlighting of key contacts to monitoring docking calculation convergence. Full article
(This article belongs to the Special Issue Molecular Docking in Drug Design 2018)
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Open AccessArticle
A Novel Ratiometric Fluorescent Probe for Mercury (II) ions and Application in Bio-imaging
Molecules 2019, 24(12), 2268; https://doi.org/10.3390/molecules24122268 (registering DOI)
Received: 29 April 2019 / Revised: 13 May 2019 / Accepted: 15 May 2019 / Published: 18 June 2019
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Abstract
Since the accumulation of mercury (II) ions in the environment and ecosystem causes serious problems to environment and disease, the recognition of Hg2+ ions and its bio-imaging is of high importance. In sight of the advantages of fluorescence probes, a new probe [...] Read more.
Since the accumulation of mercury (II) ions in the environment and ecosystem causes serious problems to environment and disease, the recognition of Hg2+ ions and its bio-imaging is of high importance. In sight of the advantages of fluorescence probes, a new probe (PMH) was facilely synthesized by incorporating phenylimidazole fluorophore and 3-methyl-2- benzothiazolinone hydrazone hydrochloride monohydrate. The PMH probe exhibited a ratiometric response for Hg2+ ions with fluorescence intensity increasing at 520 nm and decreasing at 445 nm simultaneously. The PMH probe interacted with Hg2+ ions in seconds with high optical stability and showed good selectivity over other metal ions. In addition, the probe has excellent biocompatibility and imaging performance in cells and zebrafish. Full article
(This article belongs to the Special Issue Probes for Detection, Sensing and Imaging)
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Open AccessArticle
Heterologous Expression of Ilicicolin H Biosynthetic Gene Cluster and Production of a New Potent Antifungal Reagent, Ilicicolin J
Molecules 2019, 24(12), 2267; https://doi.org/10.3390/molecules24122267 (registering DOI)
Received: 26 April 2019 / Revised: 10 June 2019 / Accepted: 12 June 2019 / Published: 18 June 2019
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Abstract
Ilicicolin H is a broad-spectrum antifungal agent targeting mitochondrial cytochrome bc1 reductase. Unfortunately, ilicicolin H shows reduced activities in vivo. Here, we report our effort on the identification of ilicicolin H biosynthetic gene cluster (BGC) by genomic sequencing a producing strain, Neonectria sp. [...] Read more.
Ilicicolin H is a broad-spectrum antifungal agent targeting mitochondrial cytochrome bc1 reductase. Unfortunately, ilicicolin H shows reduced activities in vivo. Here, we report our effort on the identification of ilicicolin H biosynthetic gene cluster (BGC) by genomic sequencing a producing strain, Neonectria sp. DH2, and its heterologous production in Aspergillus nidulans. In addition, a shunt product with similar antifungal activities, ilicicolin J, was uncovered. This effort would provide a base for future combinatorial biosynthesis of ilicicolin H analogues. Bioinformatics analysis suggests that the backbone of ilicicolin H is assembled by a polyketide-nonribosomal peptide synthethase (IliA), and then offloaded with a tetramic acid moiety. Similar to tenellin biosynthesis, the tetramic acid is then converted to pyridone by a putative P450, IliC. The decalin portion is most possibly constructed by a S-adenosyl-l-methionine (SAM)-dependent Diels-Alderase (IliD). Full article
(This article belongs to the Section Natural Products Chemistry)
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Open AccessArticle
Mechanism Investigation of Tagetes patula L. against Chronic Nonbacterial Prostatitis by Metabolomics and Network Pharmacology
Molecules 2019, 24(12), 2266; https://doi.org/10.3390/molecules24122266 (registering DOI)
Received: 21 May 2019 / Revised: 15 June 2019 / Accepted: 17 June 2019 / Published: 18 June 2019
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Abstract
The major objective of this study was to investigate the anti-chronic nonbacterial prostatitis (CNP) mechanism of T. patula by metabolomics and network pharmacology. The study demonstrated that the flavonoids and polysaccharides of T. patula could alleviate prostatitis by improving the level of DHT, [...] Read more.
The major objective of this study was to investigate the anti-chronic nonbacterial prostatitis (CNP) mechanism of T. patula by metabolomics and network pharmacology. The study demonstrated that the flavonoids and polysaccharides of T. patula could alleviate prostatitis by improving the level of DHT, reducing the secretion of PSA and TNF-α. Besides, both could enhance Na+/K+-ATPase activity, decrease the O2 consumption, CO2 production, heat production, energy expenditure of rats and promote respiratory exchange ratio of rats. Up to 28 potential biomarkers and 8 key metabolic pathways related to the treatment of CNP were elucidated by the metabolomics analysis, including phenylalanine metabolism, taurine and hypotaurine metabolism, tryptophan metabolism etc. Network pharmacology prediction also reflected the potential mechanism was associated with tryptophan metabolism and energy pathway. Generally, the potential anti-CNP mechanism of flavonoids and polysaccharides of T. patula might be through reducing the expression of inflammation factors, adjusting the level of hormone and regulating the amino acid metabolism, energy metabolism and glucose and lipid metabolism. Full article
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Open AccessReview
Inhibitory Antibodies Designed for Matrix Metalloproteinase Modulation
Molecules 2019, 24(12), 2265; https://doi.org/10.3390/molecules24122265 (registering DOI)
Received: 7 May 2019 / Revised: 13 June 2019 / Accepted: 14 June 2019 / Published: 18 June 2019
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Abstract
The family of matrix metalloproteinases (MMPs) consists of a set of biological targets that are involved in a multitude of severe pathogenic events such as different forms of cancers or arthritis. Modulation of the target class with small molecule drugs has not led [...] Read more.
The family of matrix metalloproteinases (MMPs) consists of a set of biological targets that are involved in a multitude of severe pathogenic events such as different forms of cancers or arthritis. Modulation of the target class with small molecule drugs has not led to the anticipated success until present, as all clinical trials failed due to unacceptable side effects or a lack of therapeutic outcome. Monoclonal antibodies offer a tremendous therapeutic potential given their high target selectivity and good pharmacokinetic profiles. For the treatment of a variety of diseases there are already antibody therapies available and the number is increasing. Recently, several antibodies were developed for the selective inhibition of single MMPs that showed high potency and were therefore investigated in in vivo studies with promising results. In this review, we highlight the progress that has been achieved toward the design of inhibitory antibodies that successfully modulate MMP-9 and MMP-14. Full article
(This article belongs to the Special Issue Drug Design)
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Open AccessArticle
Induced Aggregation of Epoxy Polysiloxane Grafted Gelatin by Organic Solvent and Green Application
Molecules 2019, 24(12), 2264; https://doi.org/10.3390/molecules24122264 (registering DOI)
Received: 15 May 2019 / Revised: 17 June 2019 / Accepted: 17 June 2019 / Published: 18 June 2019
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Abstract
In this paper, we studied the aggregation of amphiphilic polymer epoxy-terminated polydimethylsiloxane (PDMS-E) grafted gelatin (PGG) in water induced by methanol, ethanol, 2-propanol, acetone, tetrahydrofuran (THF), and 1,4-dioxane. The aggregation pattern of the polymer was monitored by infrared spectroscopy, X-ray diffraction, transmission electron [...] Read more.
In this paper, we studied the aggregation of amphiphilic polymer epoxy-terminated polydimethylsiloxane (PDMS-E) grafted gelatin (PGG) in water induced by methanol, ethanol, 2-propanol, acetone, tetrahydrofuran (THF), and 1,4-dioxane. The aggregation pattern of the polymer was monitored by infrared spectroscopy, X-ray diffraction, transmission electron microscopy, and scanning electron microscopy. It was revealed that the aggregate morphology showed clear dependence on the solvent polarity. The PGG aggregates had regular spherical morphology in polar solvents, including water, methanol, ethanol, 2-propanol, and acetone. The coating performance was evaluated by X-ray photoelectron spectroscopy and friction experiment, and PGG and acetone coating exhibited excellent coating performance on the surface of pigskin. Gel was formed in acetone and tetrahydrofuran (THF) with the slow evaporation of solvent, and this property can possibly be applied to industrial sewage treatment. White precipitate and soft film were formed in non-polar 1,4-dioxane. Full article
(This article belongs to the Special Issue Gelatin: Chemistry, Characterization, Application)
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Open AccessReview
Review on Carbon/Polyaniline Hybrids: Design and Synthesis for Supercapacitor
Molecules 2019, 24(12), 2263; https://doi.org/10.3390/molecules24122263 (registering DOI)
Received: 29 May 2019 / Revised: 14 June 2019 / Accepted: 16 June 2019 / Published: 18 June 2019
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Abstract
Polyaniline has been widely used in high-performance pseudocapacitors, due to its low cost, easy synthesis, and high theoretical specific capacitance. However, the poor mechanical properties of polyaniline restrict its further development. Compared with polyaniline, functionalized carbon materials have excellent physical and chemical properties, [...] Read more.
Polyaniline has been widely used in high-performance pseudocapacitors, due to its low cost, easy synthesis, and high theoretical specific capacitance. However, the poor mechanical properties of polyaniline restrict its further development. Compared with polyaniline, functionalized carbon materials have excellent physical and chemical properties, such as porous structures, excellent specific surface area, good conductivity, and accessibility to active sites. However, it should not be neglected that the specific capacity of carbon materials is usually unsatisfactory. There is an effective strategy to combine carbon materials with polyaniline by a hybridization approach to achieve a positive synergistic effect. After that, the energy storage performance of carbon/polyaniline hybridization material has been significantly improved, making it a promising and important electrode material for supercapacitors. To date, significant progress has been made in the synthesis of various carbon/polyaniline binary composite electrode materials. In this review, the corresponding properties and applications of polyaniline and carbon hybrid materials in the energy storage field are briefly reviewed. According to the classification of different types of functionalized carbon materials, this article focuses on the recent progress in carbon/polyaniline hybrid materials, and further analyzes their corresponding properties to provide guidance for the design, synthesis, and component optimization for high-performance supercapacitors. Full article
(This article belongs to the Special Issue Electrode Materials and Electrolytes in Supercapacitors)
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Open AccessArticle
Investigation of the Binding Affinity of a Broad Array of l-Fucosides with Six Fucose-Specific Lectins of Bacterial and Fungal Origin
Molecules 2019, 24(12), 2262; https://doi.org/10.3390/molecules24122262 (registering DOI)
Received: 25 April 2019 / Revised: 4 June 2019 / Accepted: 14 June 2019 / Published: 18 June 2019
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Abstract
Series of multivalent α-l-fucoside containing glycoclusters and variously decorated l-fucosides were synthesized to find potential inhibitors of fucose-specific lectins and study the structure-binding affinity relationships. Tri- and tetravalent fucoclusters were built using copper-mediated azide-alkyne click chemistry. Series of fucoside monomers [...] Read more.
Series of multivalent α-l-fucoside containing glycoclusters and variously decorated l-fucosides were synthesized to find potential inhibitors of fucose-specific lectins and study the structure-binding affinity relationships. Tri- and tetravalent fucoclusters were built using copper-mediated azide-alkyne click chemistry. Series of fucoside monomers and dimers were synthesized using various methods, namely glycosylation, an azide-alkyne click reaction, photoinduced thiol-en addition, and sulfation. The interactions between compounds with six fucolectins of bacterial or fungal origin were tested using a hemagglutination inhibition assay. As a result, a tetravalent, α-l-fucose presenting glycocluster showed to be a ligand that was orders of magnitude better than a simple monosaccharide for tested lectins in most cases, which can nominate it as a universal ligand for studied lectins. This compound was also able to inhibit the adhesion of Pseudomonas aeruginosa cells to human epithelial bronchial cells. A trivalent fucocluster with a protected amine functional group also seems to be a promising candidate for designing glycoconjugates and chimeras. Full article
(This article belongs to the Special Issue Functional Aspects of Lectins)
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Open AccessArticle
Antiproliferative Benzoindazolequinones as Potential Cyclooxygenase-2 Inhibitors
Molecules 2019, 24(12), 2261; https://doi.org/10.3390/molecules24122261 (registering DOI)
Received: 22 May 2019 / Revised: 6 June 2019 / Accepted: 15 June 2019 / Published: 18 June 2019
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Abstract
Quinones and nitrogen heterocyclic moieties have been recognized as important pharmacophores in the development of antitumor agents. This study aimed to establish whether there was any correlation between the in silico predicted parameters and the in vitro antiproliferative activity of a family of [...] Read more.
Quinones and nitrogen heterocyclic moieties have been recognized as important pharmacophores in the development of antitumor agents. This study aimed to establish whether there was any correlation between the in silico predicted parameters and the in vitro antiproliferative activity of a family of benzoindazolequinones (BIZQs), and to evaluate overexpressed proteins in human cancer cells as potential biomolecular targets of these compounds. For this purpose, this study was carried out using KATO-III and MCF-7 cell lines as in vitro models. Docking results showed that these BIZQs present better binding energies (ΔGbin) values for cyclooxygenase-2 (COX-2) than for other cancer-related proteins. The predicted ∆Gbin values of these BIZQs, classified in three series, positively correlated with IC50 measured in both cell lines (KATO-III: 0.72, 0.41, and 0.90; MCF-7: 0.79, 0.55, and 0.87 for Series I, II, and III, respectively). The results also indicated that compounds 2a, 2c, 6g, and 6k are the most prominent BIZQs, because they showed better IC50 and ∆Gbin values than the other derivatives. In silico drug absorption, distribution, metabolism, and excretion (ADME) properties of the three series were also analyzed and showed that several BIZQs could be selected as potential candidates for cancer pre-clinical assays. Full article
(This article belongs to the Special Issue Application of Organic Synthesis to Bioactive Compounds)
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Open AccessFeature PaperArticle
Evaluation of In-Batch and In-Flow Synthetic Strategies towards the Stereoselective Synthesis of a Fluorinated Analogue of Retro-Thiorphan
Molecules 2019, 24(12), 2260; https://doi.org/10.3390/molecules24122260 (registering DOI)
Received: 8 May 2019 / Revised: 10 June 2019 / Accepted: 12 June 2019 / Published: 18 June 2019
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Abstract
A stereoselective synthetic strategy for the preparation of trifluoromethylamine mimics of retro-thiorphan, involving a diastereoselective, metal-free catalytic step, has been studied in batch and afforded the target molecule in good yields and high diastereoselectivity. A crucial point of the synthetic sequence was the [...] Read more.
A stereoselective synthetic strategy for the preparation of trifluoromethylamine mimics of retro-thiorphan, involving a diastereoselective, metal-free catalytic step, has been studied in batch and afforded the target molecule in good yields and high diastereoselectivity. A crucial point of the synthetic sequence was the catalytic reduction of a fluorinated enamine with trichlorosilane as reducing agent in the presence of a chiral Lewis base. The absolute configuration of the key intermediate was unambiguously assigned by X-ray analysis. The synthesis was also investigated exploiting continuous flow reactions; that is, an advanced intermediate of the target molecule was synthesized in only two in-flow synthetic modules, avoiding isolation and purifications of intermediates, leading to the isolation of the target chiral fluorinated amine in up to an 87:13 diastereoisomeric ratio. Full article
(This article belongs to the Special Issue Flow Chemistry in Organic Synthesis)
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Open AccessArticle
Synthesis and Properties of New Dithienosilole Derivatives as Luminescent Materials
Molecules 2019, 24(12), 2259; https://doi.org/10.3390/molecules24122259
Received: 23 May 2019 / Revised: 11 June 2019 / Accepted: 13 June 2019 / Published: 17 June 2019
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Abstract
Three new organosilicon compounds based on dithienosilole (DTSi) were synthesized in good yields. We report the optical and electrochemical properties of the resulting derivatives. We find that these compounds absorb the light in the ultraviolet and blue light range, and they exhibit luminescence [...] Read more.
Three new organosilicon compounds based on dithienosilole (DTSi) were synthesized in good yields. We report the optical and electrochemical properties of the resulting derivatives. We find that these compounds absorb the light in the ultraviolet and blue light range, and they exhibit luminescence in almost the entire range of visible light. After electropolymerization were significantly lowered, the values of the energy gap (even 1.51 eV for P2) and the ionization potential of the polymers were compared to monomers. Optoelectronic properties of the obtained compounds suggest that these derivatives of DTSi may be good candidates as the emissive layers in white organic light-emitting diodes (WOLEDs), which would reduce the amount of layers. Full article
(This article belongs to the Special Issue Synthesis of Functional Silicon Compounds)
Open AccessArticle
Structural Characterization of Arabidopsis thaliana NAP1-Related Protein 2 (AtNRP2) and Comparison with its Homolog AtNRP1
Molecules 2019, 24(12), 2258; https://doi.org/10.3390/molecules24122258
Received: 9 May 2019 / Revised: 2 June 2019 / Accepted: 4 June 2019 / Published: 17 June 2019
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Abstract
Nucleosome Assembly Protein (NAP) is a highly conserved family of histone chaperones present in yeast, animals, and plants. Unlike other organisms, plants possess an additional class of proteins in its NAP family, known as the NAP1-related proteins or NRP. Arabidopsis thaliana possesses two [...] Read more.
Nucleosome Assembly Protein (NAP) is a highly conserved family of histone chaperones present in yeast, animals, and plants. Unlike other organisms, plants possess an additional class of proteins in its NAP family, known as the NAP1-related proteins or NRP. Arabidopsis thaliana possesses two NRP isoforms, namely AtNRP1 and AtNRP2, that share 87% sequence identity. Both AtNRP1 and AtNRP2 get expressed in all the plant tissues. Most works in the past, including structural studies, have focused on AtNRP1. We wanted to do a comparative study of the two proteins to find why the plant would have two very similar proteins and whether there is any difference between the two for their structure and function as histone chaperones. Here we report the crystal structure of AtNRP2 and a comparative analysis of its structural architecture with other NAP family proteins. The crystal structure of AtNRP2 shows it to be a homodimer, with its fold similar to that of other structurally characterized NAP family proteins. Although AtNRP1 and AtNRP2 have a similar fold, upon structural superposition, we find an offset in the dimerization helix of the two proteins. We evaluated the stability, oligomerization status, and histone chaperoning properties of the two proteins, for a comparison. The thermal melting experiments suggest that AtNRP2 is more stable than AtNRP1 at higher temperatures. In addition, electrophoretic mobility shift assay and isothermal titration calorimetry experiments suggest histone binding ability of AtNRP2 is higher than that of AtNRP1. Overall, these results provide insights about the specific function and relevance of AtNRP2 in plants through structural and biophysical studies. Full article
(This article belongs to the Special Issue Frontier of Protein Crystallography)
Open AccessArticle
Conformation and Dynamics of the Cyclic Lipopeptide Viscosinamide at the Water-Lipid Interface
Molecules 2019, 24(12), 2257; https://doi.org/10.3390/molecules24122257
Received: 18 May 2019 / Revised: 11 June 2019 / Accepted: 13 June 2019 / Published: 17 June 2019
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Abstract
Cyclic lipodepsipeptides or CLiPs from Pseudomonas are secondary metabolites that mediate a wide range of biological functions for their producers, and display antimicrobial and anticancer activities. Direct interaction of CLiPs with the cellular membranes is presumed to be essential in causing these. To [...] Read more.
Cyclic lipodepsipeptides or CLiPs from Pseudomonas are secondary metabolites that mediate a wide range of biological functions for their producers, and display antimicrobial and anticancer activities. Direct interaction of CLiPs with the cellular membranes is presumed to be essential in causing these. To understand the processes involved at the molecular level, knowledge of the conformation and dynamics of CLiPs at the water-lipid interface is required to guide the interpretation of biophysical investigations in model membrane systems. We used NMR and molecular dynamics to study the conformation, location and orientation of the Pseudomonas CLiP viscosinamide in a water/dodecylphosphocholine solution. In the process, we demonstrate the strong added value of combining uniform, isotope-enriched viscosinamide and protein NMR methods. In particular, the use of techniques to determine backbone dihedral angles and detect and identify long-lived hydrogen bonds, establishes that the solution conformation previously determined in acetonitrile is maintained in water/dodecylphosphocholine solution. Paramagnetic relaxation enhancements pinpoint viscosinamide near the water-lipid interface, with its orientation dictated by the amphipathic distribution of hydrophobic and hydrophilic residues. Finally, the experimental observations are supported by molecular dynamics simulations. Thus a firm structural basis is now available for interpreting biophysical and bioactivity data relating to this class of compounds. Full article
(This article belongs to the Special Issue Cyclic Peptide Analogues and Non-Peptide Mimetics)
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Open AccessArticle
Paradoxical Patterns of Sinusoidal Obstruction Syndrome-Like Liver Injury in Aged Female CD-1 Mice Triggered by Cannabidiol-Rich Cannabis Extract and Acetaminophen Co-Administration
Molecules 2019, 24(12), 2256; https://doi.org/10.3390/molecules24122256
Received: 21 May 2019 / Revised: 6 June 2019 / Accepted: 13 June 2019 / Published: 17 June 2019
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Abstract
The goal of this study was to investigate the potential for a cannabidiol-rich cannabis extract (CRCE) to interact with the most common over-the-counter drug and the major known cause of drug-induced liver injury–acetaminophen (APAP)–in aged female CD-1 mice. Gavaging mice with 116 mg/kg [...] Read more.
The goal of this study was to investigate the potential for a cannabidiol-rich cannabis extract (CRCE) to interact with the most common over-the-counter drug and the major known cause of drug-induced liver injury–acetaminophen (APAP)–in aged female CD-1 mice. Gavaging mice with 116 mg/kg of cannabidiol (CBD) [mouse equivalent dose (MED) of 10 mg/kg of CBD] in CRCE delivered with sesame oil for three consecutive days followed by intraperitoneally (i.p.) acetaminophen (APAP) administration (400 mg/kg) on day 4 resulted in overt toxicity with 37.5% mortality. No mortality was observed in mice treated with 290 mg/kg of CBD+APAP (MED of 25 mg/kg of CBD) or APAP alone. Following CRCE/APAP co-administration, microscopic examination revealed a sinusoidal obstruction syndrome-like liver injury–the severity of which correlated with the degree of alterations in physiological and clinical biochemistry end points. Mechanistically, glutathione depletion and oxidative stress were observed between the APAP-only and co-administration groups, but co-administration resulted in much greater activation of c-Jun N-terminal kinase (JNK). Strikingly, these effects were not observed in mice gavaged with 290 mg/kg CBD in CRCE followed by APAP administration. These findings highlight the potential for CBD/drug interactions, and reveal an interesting paradoxical effect of CBD/APAP-induced hepatotoxicity. Full article
(This article belongs to the Special Issue Cytotoxic Activity of Plant Extracts)
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Open AccessArticle
In Vitro and In Vivo Anti-Breast Cancer Activities of Some Newly Synthesized 5-(thiophen-2-yl)thieno-[2,3-d]pyrimidin-4-one Candidates
Molecules 2019, 24(12), 2255; https://doi.org/10.3390/molecules24122255
Received: 29 May 2019 / Revised: 13 June 2019 / Accepted: 14 June 2019 / Published: 17 June 2019
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Abstract
In this study, some of new thiophenyl thienopyrimidinone derivatives 215 were prepared and tested as anti-cancer agents by using thiophenyl thieno[2,3-d]pyrimidinone derivative 2 as a starting material, which was prepared from cyclization of ethyl ester derivative 1 with formamide. Treatment of [...] Read more.
In this study, some of new thiophenyl thienopyrimidinone derivatives 215 were prepared and tested as anti-cancer agents by using thiophenyl thieno[2,3-d]pyrimidinone derivative 2 as a starting material, which was prepared from cyclization of ethyl ester derivative 1 with formamide. Treatment of 2 with ethyl- chloroacetate gave thienopyrimidinone N-ethylacetate 3, which was reacted with hydrazine hydrate or anthranilic acid to afford acetohydrazide 4 and benzo[d][1,3]oxazin-4-one 5, respectively. Condensation of 4 with aromatic aldehydes or phenylisothiocyanate yielded Schiff base derivatives 6,7, and thiosemicarbazise 10, which were treated with 2-mercaptoacetic acid or chloroacetic acid to give the corresponding thiazolidinones 8, 9, and phenylimino-thiazolidinone 11, respectively. Treatment of 4 with ethylacetoacetate or acetic acid/acetic anhydride gave pyrazole 12 and acetyl acetohydrazide 13 derivatives, respectively. The latter compound 13 was reacted with ethyl cycno-acetate or malononitrile to give 14 and 15, respectively. In this work, we have studied the anti-cancer activity of the synthesized thienopyrimidinone derivatives against MCF-7 and MCF-10A cancer cells. Furthermore, in vivo experiments showed that the synthesized compounds significantly reduced tumor growth up to the 8th day of treatment in comparison to control animal models. Additionally, the synthesized derivatives showed potential inhibitory effects against pim-1 kinase activities. Full article
(This article belongs to the Special Issue Anticancer Agents: Design, Synthesis and Evaluation)
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Open AccessArticle
Synthesis and Cytotoxicity Evaluation of DOTA-Conjugates of Ursolic Acid
Molecules 2019, 24(12), 2254; https://doi.org/10.3390/molecules24122254
Received: 12 May 2019 / Revised: 7 June 2019 / Accepted: 14 June 2019 / Published: 17 June 2019
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Abstract
In this study, we report the synthesis of several amine-spacered conjugates of ursolic acid (UA) and 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA). Thus, a total of 11 UA-DOTA conjugates were prepared holding various oligo-methylene diamine spacers as well as different substituents at the acetate units of [...] Read more.
In this study, we report the synthesis of several amine-spacered conjugates of ursolic acid (UA) and 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA). Thus, a total of 11 UA-DOTA conjugates were prepared holding various oligo-methylene diamine spacers as well as different substituents at the acetate units of DOTA including tert-butyl, benzyl, and allyl esters. Furthermore, three synthetic approaches were compared for the ethylenediamine-spacered conjugate 29 regarding reaction steps, yields, and precursor availability. The prepared conjugates were investigated regarding cytotoxicity using SRB assays and a set of human tumor cell lines. The highest cytotoxicity was observed for piperazinyl spacered compound 22. Thereby, EC50 values of 1.5 µM (for A375 melanoma) and 1.7 µM (for A2780 ovarian carcinoma) were determined. Conjugates 22 and 24 were selected for further cytotoxicity investigations including fluorescence microscopy, annexin V assays and cell cycle analysis. Full article
(This article belongs to the Special Issue Antitumor and Anti-HIV Agents from Natural Products)
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Open AccessArticle
Metabolic Effect of Dietary Taurine Supplementation on Grouper (Epinephelus coioides): A 1H-NMR-Based Metabolomics Study
Molecules 2019, 24(12), 2253; https://doi.org/10.3390/molecules24122253
Received: 22 May 2019 / Revised: 14 June 2019 / Accepted: 16 June 2019 / Published: 17 June 2019
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Abstract
Taurine is an indispensable amino acid for many fish species and taurine supplementation is needed when plant-based diets are used as the primary protein source for these species. However, there is limited information available to understand the physiological or metabolic effects of taurine [...] Read more.
Taurine is an indispensable amino acid for many fish species and taurine supplementation is needed when plant-based diets are used as the primary protein source for these species. However, there is limited information available to understand the physiological or metabolic effects of taurine on fish. In this study, 1H nuclear magnetic resonance (NMR)-based metabolomic analysis was conducted to identify the metabolic profile change in the fish intestine with the aim to assess the effect of dietary taurine supplementation on the physiological and metabolomic variation of fish, and reveal the possible mechanism of taurine’s metabolic effect. Grouper (Epinephelus coioides) were divided into four groups and fed diets containing 0.0%, 0.5%, 1.0%, and 1.5% taurine supplementation for 84 days. After extraction using aqueous and organic solvents, 25 significant taurine-induced metabolic changes were identified. These metabolic changes in grouper intestine were characterized by differences in carbohydrate, amino acid, lipid and nucleotide. The results reflected both the physiological state and growth of the fish, and indicated that taurine supplementation significantly affects the metabolome of fish, improves energy utilization and amino acid uptake, promotes protein, lipid and purine synthesis, and accelerates fish growth. Full article
(This article belongs to the Special Issue Modern Analytical Techniques in Metabolomics Analysis)
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Open AccessArticle
Tautomerism in Azo and Azomethyne Dyes: When and If Theory Meets Experiment
Molecules 2019, 24(12), 2252; https://doi.org/10.3390/molecules24122252
Received: 3 June 2019 / Revised: 13 June 2019 / Accepted: 14 June 2019 / Published: 17 June 2019
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Abstract
The performance of 26 hybrid density functionals was tested against a tautomeric dataset (TautData), containing experimental information for the keto-enol tautomeric equilibrium in 16 tautomeric azodyes and Schiff bases in cyclohexane, carbon tetrachloride and acetonitrile. The results have shown that MN12-SX, BHandH and [...] Read more.
The performance of 26 hybrid density functionals was tested against a tautomeric dataset (TautData), containing experimental information for the keto-enol tautomeric equilibrium in 16 tautomeric azodyes and Schiff bases in cyclohexane, carbon tetrachloride and acetonitrile. The results have shown that MN12-SX, BHandH and M06-2X can be used to describe the tautomeric state of the core structures in the frame of ~0.5 kcal/mol error and correctly predict the tautomeric state in respect of dominating tautomeric form. Among them MN12-SX is the best performer, although it fails to describe the nonplanarity of some of the enol tautomers. The same experimental dataset was used to develop and test a special DFT functional (TautLYP) aimed at describing the tautomeric state in azo- and azomethyne compounds in solution when nonspecific solvents are used. Full article
(This article belongs to the Special Issue Tautomerism and Proton Transfer Related Phenomena)
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Open AccessArticle
Quality Assessment of Commercial Spagyric Tinctures of Harpagophytum procumbens and Their Antioxidant Properties
Molecules 2019, 24(12), 2251; https://doi.org/10.3390/molecules24122251
Received: 26 March 2019 / Revised: 10 June 2019 / Accepted: 14 June 2019 / Published: 17 June 2019
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Abstract
Preparations from the dried tubers of Harpagophytum procumbens (Burch.) DC ex Meisn, commonly known as devil’s claw, are mainly used in modern medicine to relieve joint pain and inflammation in patients suffering from rheumatic and arthritic disorders. This paper describes for the first [...] Read more.
Preparations from the dried tubers of Harpagophytum procumbens (Burch.) DC ex Meisn, commonly known as devil’s claw, are mainly used in modern medicine to relieve joint pain and inflammation in patients suffering from rheumatic and arthritic disorders. This paper describes for the first time the chemical profile of a commercial spagyric tincture (named 019) prepared from the roots of the plant. For comparison purposes, a commercial not-spagyric devil’s claw tincture (NST) was also analyzed. Chemical investigation of the content of specialized metabolites in the three samples indicated that harpagoside was the main compound, followed by the two isomers acteoside and isoacteoside. Compositional consistence over time was obtained by the chemical fingerprinting of another spagyric tincture (named 014) from the same producer that was already expired according to the recommendation on the label of the product. The two spagyric preparations did not show significant compositional differences as revealed by HPLC and MS analyses, except for a decrease in harpagide content in the expired 014 tincture. Moreover, their antioxidant capacities as assessed by 2,2’-di-phenyl-1-picrylhydrazyl (DPPH) and 2.2’-azin-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) methods resulted in very similar IC50 values. The expired 014 tincture showed instead a lower IC50 value compared to the 019 and NST tinctures with the ferric reducing antioxidant potential (FRAP) assay, indicating a higher ferric-reducing antioxidant ability. Overall, these results indicated that the two preparations could generally maintain good stability and biological activity at least for the four years from the production to the expiration date. Full article
(This article belongs to the Special Issue Natural Products and Drug Discovery)
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Open AccessReview
Liquefaction of Biomass and Upgrading of Bio-Oil: A Review
Molecules 2019, 24(12), 2250; https://doi.org/10.3390/molecules24122250
Received: 22 May 2019 / Revised: 6 June 2019 / Accepted: 14 June 2019 / Published: 17 June 2019
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Abstract
The liquefaction of biomass is an important technology to converse the biomass into valuable biofuel. The common technologies for liquefaction of biomass are indirect liquefaction and direct liquefaction. The indirect liquefaction refers to the Fischer–Tropsch (F–T) process using the syngas of biomass as [...] Read more.
The liquefaction of biomass is an important technology to converse the biomass into valuable biofuel. The common technologies for liquefaction of biomass are indirect liquefaction and direct liquefaction. The indirect liquefaction refers to the Fischer–Tropsch (F–T) process using the syngas of biomass as the raw material to produce the liquid fuel, including methyl alcohol, ethyl alcohol, and dimethyl ether. The direct liquefaction of biomass refers to the conversion biomass into bio-oil, and the main technologies are hydrolysis fermentation and thermodynamic liquefaction. For thermodynamic liquefaction, it could be divided into fast pyrolysis and hydrothermal liquefaction. In addition, this review provides an overview of the physicochemical properties and common upgrading methods of bio-oil. Full article
(This article belongs to the Special Issue Biorefineries)
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Open AccessArticle
2-Iodo-4′-Methoxychalcone Attenuates Methylglyoxal-Induced Neurotoxicity by Activation of GLP-1 Receptor and Enhancement of Neurotrophic Signal, Antioxidant Defense and Glyoxalase Pathway
Molecules 2019, 24(12), 2249; https://doi.org/10.3390/molecules24122249
Received: 31 May 2019 / Revised: 14 June 2019 / Accepted: 15 June 2019 / Published: 16 June 2019
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Abstract
Methylglyoxal (MG) acts as a reactive precursor of advanced glycation end products (AGEs). This compound is often connected with pathologies such as diabetes, neurodegenerative processes and diseases of aging. 2-iodo-4′-methoxychalcone (CHA79), a synthetic halogen-containing chalcone derivative, has been reported its anti-diabetic activity. This [...] Read more.
Methylglyoxal (MG) acts as a reactive precursor of advanced glycation end products (AGEs). This compound is often connected with pathologies such as diabetes, neurodegenerative processes and diseases of aging. 2-iodo-4′-methoxychalcone (CHA79), a synthetic halogen-containing chalcone derivative, has been reported its anti-diabetic activity. This study aims to investigate the potential protective capability of CHA79 against MG-mediated neurotoxicity in SH-SY5Y cells. Results indicated CHA79 increased viability of cells and attenuated the rate of apoptosis in MG-exposed SH-SY5Y. CHA79 up-regulated expression of anti-apoptotic protein (Bcl-2) and down-regulated apoptotic proteins (Bax, cytochrome c, caspase-3, caspase-9). Moreover, CHA79 significantly up-regulated expression of neurotrophic factors, including glucagon-like peptide-1 receptor (GLP-1R), brain derived neurotrophic factor (BDNF), p75NTR, p-TrkB, p-Akt, p-GK-3β and p-CREB. CHA79 attenuated MG-induced ROS production and enhanced the antioxidant defense including nuclear factor erythroid 2-related factor 2 (Nrf2), HO-1, SOD and GSH. Furthermore, CHA79 attenuated MG-induced reduction of glyoxalase-1 (GLO-1), a vital enzyme on removing AGE precursors. In conclusion, CHA79 is the first novel synthetic chalcone possessing the GLP-1R and GLO-1 activating properties. CHA 79 also exhibits neuroprotective effects against MG toxicity by enhancing neurotrophic signal, antioxidant defense and anti-apoptosis pathway. Full article
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Open AccessArticle
The Amphoteric and Hydrophilic Properties of Cartilage Surface in Mammalian Joints: Interfacial Tension and Molecular Dynamics Simulation Studies
Molecules 2019, 24(12), 2248; https://doi.org/10.3390/molecules24122248
Received: 24 April 2019 / Revised: 7 June 2019 / Accepted: 15 June 2019 / Published: 16 June 2019
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Abstract
In this paper, we explain the amphoteric character of the cartilage surface by studying a lipid bilayer model built from phospholipids. We examined the interfacial tension values and molecular dynamics simulation in solutions of varying pH. The effects of negative and positive charge [...] Read more.
In this paper, we explain the amphoteric character of the cartilage surface by studying a lipid bilayer model built from phospholipids. We examined the interfacial tension values and molecular dynamics simulation in solutions of varying pH. The effects of negative and positive charge density (or fixed charges) on the (cartilage/cartilage) friction coefficient were investigated. In physiological (or synovial) fluid, after the isoelectric point (pI), the curve of interfacial tension decreases rapidly as it reaches pH 7.4 and then approaches a constant value at higher pH. It was shown that the curve of the interfacial tension curve exhibits a maximum value at the isoelectric point with a Gaussian shape feature. The phospholipid bilayers facilitate an almost frictionless contact in the joint. Moreover, the slippage of the bilayer and the short-range repulsion between the surfaces of the negatively charged cartilage surfaces are the main determinants of the low frictional properties of the joint. Full article
(This article belongs to the Section Physical Chemistry)
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Open AccessArticle
Solid State and Solution Study on the Formation of Inorganic Anion Complexes with a Series of Tetrazine-Based Ligands
Molecules 2019, 24(12), 2247; https://doi.org/10.3390/molecules24122247
Received: 22 May 2019 / Revised: 13 June 2019 / Accepted: 14 June 2019 / Published: 16 June 2019
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Abstract
Four molecules (L1–L4) constituted by an s-tetrazine ring appended with two identical aliphatic chains of increasing length bearing terminal morpholine groups were studied as anion receptors in water. The basicity properties of these molecules were also investigated. Speciation of the anion complexes formed [...] Read more.
Four molecules (L1–L4) constituted by an s-tetrazine ring appended with two identical aliphatic chains of increasing length bearing terminal morpholine groups were studied as anion receptors in water. The basicity properties of these molecules were also investigated. Speciation of the anion complexes formed in solution and determination of their stability constants were performed by means of potentiometric (pH-metric) titrations, while further information was obtained by NMR and isothermal titration calorimetry (ITC) measurements. The crystal structures of two neutral ligands (L3, L4) and of their H2L3(ClO4)2∙2H2O, H2L4(ClO4)2∙2H2O, H2L3(PF6)2, and H2L3(PF6)2∙2H2O anion complexes were determined by single crystal X-ray diffraction. The formation of anion–π interactions is the leitmotiv of these complexes, both in solution and in the solid state, although hydrogen bonding and/or formation of salt-bridges can contribute to their stability. Evidence of the ability of these ligands to form anion–π interactions is given by the observation that even the neutral (not-protonated) molecules bind anions in water to form complexes of significant stability, including elusive OH anions. Full article
(This article belongs to the Section Inorganic Chemistry)
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Open AccessArticle
Benzophenones from Anemarrhena asphodeloides Bge. Exhibit Anticancer Activity in HepG2 Cells via the NF-κB Signaling Pathway
Molecules 2019, 24(12), 2246; https://doi.org/10.3390/molecules24122246
Received: 28 May 2019 / Revised: 11 June 2019 / Accepted: 13 June 2019 / Published: 15 June 2019
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Abstract
A chemical investigation of the fibrous roots of Anemarrhena asphodeloides Bge. led to the isolation of four benzophenones, including one new compound (1) and three known ones (2–4). Comprehensive 1D, 2D NMR and HRESIMS data established the [...] Read more.
A chemical investigation of the fibrous roots of Anemarrhena asphodeloides Bge. led to the isolation of four benzophenones, including one new compound (1) and three known ones (2–4). Comprehensive 1D, 2D NMR and HRESIMS data established the structures of the isolated compounds. The absolute configurations were determined by comparison of the calculated optical rotation (OR) with experimental data. All the isolates were evaluated for their cytotoxicities on hepatocellular carcinoma cell lines (HepG2 and Hep3B). Compound 1 showed strong cytotoxicity against HepG2 and Hep3B cells, with IC50 values at 153.1 and 180.6 nM. Through MTT assay, flow cytometry and Western blot analysis, compound 1 demonstrated the ability to stimulate apoptosis via the NF-κB signaling pathway in HepG2 cells. These benzophenones are potential lead compounds for the development of better treatments for hepatocellular carcinoma. Full article
(This article belongs to the Section Bioorganic Chemistry)
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Open AccessArticle
Synthesis of a Novel Zn-Salphen Building Block and Its Acrylic Terpolymer Counterparts as Tunable Supramolecular Recognition Systems
Molecules 2019, 24(12), 2245; https://doi.org/10.3390/molecules24122245
Received: 9 May 2019 / Revised: 25 May 2019 / Accepted: 30 May 2019 / Published: 15 June 2019
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Abstract
In this work, we present the synthesis of a novel Zn-Salphen complex containing an allyl group, which was used as building block in the further preparation of a new family of functional terpolymers. These polymers were obtained through radical co-polymerization with methyl metacrylate [...] Read more.
In this work, we present the synthesis of a novel Zn-Salphen complex containing an allyl group, which was used as building block in the further preparation of a new family of functional terpolymers. These polymers were obtained through radical co-polymerization with methyl metacrylate (MMA) and n-butyl acrylate (nBuA) in different ratios. The supramolecular recognition behavior of each polymer was evaluated via potentiometric measurements against selected anions in aqueous media. Interestingly, this proof of concept study shows that these systems were selective against only fluoride (F) or both, fluoride and acetate (OAc), by tailoring the relative content of Zn-Salphen monomer, thus making them a promising starting point for modular design of chemical sensors through straightforward synthetic approaches. Full article
(This article belongs to the Special Issue Molecular Recognition and Self-Assembly in Chemistry and Medicine)
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