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Alcohol-induced muscle damage (AIMD) is an umbrella term that includes all forms of alcoholic myopathy developing in acute or chronic alcohol intoxication. The most common form of destruction of skeletal muscles in alcoholism is chronic alcoholic myopathy, which develops independently of other alcohol-induced disorders, such as polyneuropathy, the malabsorption syndrome, and liver damage, but may be combined with them. The atrophy of muscle fibers underlies skeletal muscle destruction in chronic AIMD. Type II muscle fibers are affected to a greater degree than type I muscle fibers. To date, the pathogenesis of chronic alcoholic myopathy has been studied insufficiently. The imbalance between protein synthesis and proteolysis, as well as increased apoptosis rate, is discussed.

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The invention provides compounds and pharmaceutically acceptable salts and esters and compositions thereof, for treating viral infections. The compounds and compositions are useful for treating Pneumovirinae virus infection including Human respiratory syncytial virus infections.

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Background: Thiazolidinone derivatives show inhibitory activity (IC50) against the Toxoplasma gondii parasite, as well as high selectivity with high therapeutic index. To disclose the target proteins of the thiazolidinone core in this parasite, we explored in silico the active sites of different T. gondii proteins and estimated the binding-free energy of reported thiazolidinone molecules with inhibitory effect on invasion and replication of the parasite inside host cells. This enabled us to describe some of the most suitable structural characteristics to design a compound derived from the thiazolidinone core. Results: The best binding affinity was observed in the active site of kinase proteins, we selected the active site of the T. gondii ROP18 kinase, because it is an important factor for the virulence and survival of the parasite. We present the possible effect of a derivative of thiazolidinone core in the active site of T. gondii ROP18 and described some characteristics of substituent groups that could improve the affinity and specificity of compounds derived from the thiazolidinone core against T. gondii. Conclusions: The results of our study suggest that compounds derived from the thiazolidinone core have a preference for protein kinases of T. gondii, being promising compounds for the development of new drugs with potential anti-toxoplasmosis activity. Our findings highlight the importance of use computational studies for the understanding of the action mechanism of compounds with biological activity.

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The reaction of 3-substituted 2-(N-cyanoimino)thiazolidine (NCT) derivatives with hydrazine hydrate afforded two types of 1,2,4-triazoles via a selective C2-S or C2-N3 bond fission, in which the selectivity was controlled by the N3-substituent.

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We have developed new phosphorylating agents, 3-phosphono-2-(N-cyanoimino)-thiazolidine derivatives (3-phosphono-NCTs), which were readily synthesized by phosphorylation of NCT, and transformed primary and secondary alcohols into phosphates in good yield. The transfer of three kinds of dialkylphosphono groups [(PhO)2P(O)-, (EtO)2P(O)-, (Cl3CCH2O)2P(O)-] proceeded in excellent yields. Selective phosphorylation of various alcohols was also accomplished.

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A series of novel 1, 8-dioxo-octahydroxanthene derivatives containing 4-thiazolidinone framework (4a-f) were synthesized through a four-step reaction starting from the reduction of nitro derivatives of 1, 8-dioxo-octahydroxanthenes. The resulting aminoxanthenes converted to thiourea derivatives via their reaction with methyl isothiocyanate. The final products were synthesized through the reaction of thiourea derivatives with dialkylacetylene dicarboxylates. All of the steps were carried out under easy and mild reaction conditions in the absence of expensive catalysts or esoteric starting materials. The structures of compounds 3a-c and the final products were characterized according to their physical constants, spectral data such as NMR, IR spectra and also elemental analysis.

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Maresin 1 is a potent anti-inflammatory and pro-resolving lipid mediator derived from docosahexaenoic acid. The total synthesis of maresin 1 is achieved in 10 steps and in 7% overall yield. The Evans-Nagao aldol reaction between (2E,4E)-5-bromopenta-2,4-dienal and different chiral auxiliaries is investigated. The reported synthesis is efficient and highly stereoselective, affording multi-milligram quantities of this biologically interesting lipid mediator.

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Aim. Synthesis of a series of thiazolidinone-and pyrazoline-related compounds. In vitro screening of antiplasmodial activity of versatile heterocyclic derivatives. Methods: Organic wet synthesis, analytical and spectral methods, pharmacological screening, SAR analysis. Results. A series of different thiazolidinone-and pyrazoline-based derivatives was screened against Plasmodium falciparum in in vitro assays. 5-(Z)-Arylidene-2-arylidenehydrazono-3-(4-hydroxyphenyl)-4-thiazolidinones showed high growth inhibition rates with the IC50-2.32-2.39 muM. 5-Bromo-1-[2-[3-(4-chlorophenyl)-5-(4-methoxyphenyl)-3,4-dihydropyrazol-2-yl]-2-oxoethyl]indoline-2,3-dione 3 was the most active compound among tested with the IC50-1.81 muM. Based on the screening data some structure-activity relationships were derived. Conclusions. A set of different thiazolidinone-and pyrazoline-related derivatives with antitrypanosomal and anticancer properties was screened against Plasmodium falciparum. Hitcompounds inhibiting growth of the parasite at micromolar concentrations were identified. The obtained results provide further avenues to develop more potent antimalarial agents on the base of investigated classes of small drug-like molecules.

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Multidrug and toxin extruder (MATE) 1 plays a central role in mediating renal secretion of organic cations, a structurally diverse collection of compounds that includes ?40% of prescribed drugs. Because inhibition of transport activity of other multidrug transporters, including the organic cation transporter (OCT) 2, is influenced by the structure of the transported substrate, the present study screened over 400 drugs as inhibitors of the MATE1-mediated transport of four structurally distinct organic cation substrates: The commonly used drugs: 1) metformin and 2) cimetidine; and two prototypic cationic substrates, 3) 1-methyl-4-phenylpyridinium (MPP), and 4) the novel fluorescent probe, N,N,N- Trimethyl-2-[methyl(7- nitrobenzo[c][1,2,5]oxadiazol-4-yl)amino]ethanaminium iodide. Transport was measured in Chinese hamster ovary cells that stably expressed the human ortholog of MATE1. Comparison of the resulting inhibition profiles revealed no systematic influence of substrate structure on inhibitory efficacy. Similarly, IC50 values for 26 structurally diverse compounds revealed no significant influence of substrate structure on the kinetic interaction of inhibitor with MATE1. The IC50 data were used to generate three-dimensional quantitative pharmacophores that identified hydrophobic regions, H-bond acceptor sites, and an ionizable (cationic) feature as key determinants for ligand binding to MATE1. In summary, in contrast to the behavior observed with some other multidrug transporters, including OCT2, the results suggest that substrate identity exerts comparatively little influence on ligand interaction with MATE1.

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Heterocyclic compounds are generally scattered in nature and occupy a prominent location in medicinal chemistry as pharmaceuticals and drug intermediates. They play a widespread role in the metabolism of living cells, and clinically used to treat diverse sicknesses. The healing significance of heterocyclics has created a much interest in the synthesis of latest heterocyclic machine instructions to look at the sulphur and nitrogen condensed biodynamic. Reviews of the pharmacological pastime of 1,2,4- triazole derivatives are presented. a few bi-heterocyclic compounds incorporating a 1,3,4-thiazole and 1,2,four-triazole ring are presented as antimicrobial dealers.1,2,4-triazole derivatives template is a privileged fragment in cutting-edge medicinal chemistry thinking about its wide pharmacological spectrum and liking for various bio-targets. It is among the usually occurring heterocyclic nuclei in many marine in addition to herbal plant merchandise possessing a wide variety of biological packages.

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