In the modern world, liver diseases are of great relevance. It is important to search and study new drugs with a hepatoprotective effect with a simultaneous positive effect on carbohydrate and lipid metabolism. The issues of synthesis of various derivatives of cyanothioacetamide are being studied on the basis of the research laboratory "KhimEx" of the Lugansk State University named after Vladimir Dahl. As a result of preliminary experiments in silico, compounds with laboratory codes AZ-383, AZ-257, AZ-020 were selected, which have biotargets for influencing carbohydrate and lipid metabolism, as well as liver function.
The aim of the study was to study the hepatoprotective activity of thieno[2,3-b]quinoline and 1,4-dihydropyridine derivatives in a model of metabolic disorders, evaluating morphological changes, biochemical and immunohistochemical parameters of the liver.
Materials and methods of research. The experiment was carried out on 72 mature Wistar rats. Animals of the control groups were modeled metabolic disorders by high-fat diet, steroid load and their sequential combined effects. Pharmacocorrection of the induced disorders was carried out for 14 days with reference drugs (metformin and vildagliptin) and experimental compounds with codes AZ-383, AZ-257, AZ-020. When the animals were hatched, blood was taken to determine the concentration of ALT, AST, total bilirubin, histomorphometric study of the liver, immunohistochemical detection for Ki-67.
Results. All studied derivatives of alpha-cyanothioacetamide showed hepatoprotective activity, which was manifested by a significant decrease in the activity of ALT, AST, the level of total bilirubin, which were increased after prolonged alimentary and steroid loading. The ability of the compounds to neutralize the phenomena of pronounced vacuolar and fatty degeneration, necrosis of hepatocytes recorded on sections of the liver is more effective than comparators. The most pronounced proliferative activity of the liver was recorded in rats, which, after a long-term alimentary and dexamethasone load, were injected for 2 weeks with a cyanothioacetamide derivative with the code AZ-383 at a dose of 1 mg/kg.
Conclusions.New derivatives of cyanothioacetamide have hepatoprotective activity under alimentary and dexamethasone loads, which was confirmed in this study. The most pronounced hepatoprotective properties have a compound with code AZ-383 (2-methyl-N-(2-methylphenyl)-4-(2-furyl)-5-cyano-6-({2-[(4-ethoxyphenyl)amino] -2-oxoethyl}thio)-1,4-dihydropyridine-3-carboxamide).
