In silico and in vivo studies of hypoglycemic activity of novel thienopyridine and dihydropyridine derivatives
Abstract
Purpose of the study. We aimed to find and study in silico and in vivo novel thienopyridine and dihydropyridine derivatives with hypoglycemic activity. Materials and methods. Three derivatives of thienopyridine and dihydropyridine with potential hypoglycemic effect were selected from 350 novel cyanothioacetamide derivatives synthesized by the authors in the “ChemEx” Research Laboratory using virtual bioscreening based on SwissTargetPrediction software, and their oral administration safety was assessed. During the experimental study conducted on 72 mature male Wistar rats, we modeled hyperglycemia in the animals by means of high-fat diet and dexamethasone load, then we performed pharmacological correction of metabolic disorders with the novel compounds and comparison drugs - Metformin, Vildagliptin. Upon withdrawal of animals from the experiment, blood was sampled for further biochemical investigation and determination of glucose concentration, ALT, AST, total bilirubin, triglycerides, and total blood cholesterol levels. Results. The results of molecular docking showed that the novel compounds with the codes AZ-383, AZ-257, and AZ-020 have putative effects on biotargets with potential for the correction of hyperglycemia and positive impact on lipid metabolism and liver function. In addition, these compounds have a good safety profile when administered orally. In the in vivo study, compounds AZ-383, AZ-257, and AZ-020 were found to have hypoglycemic activity and associated…
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