Evaluation of the hypoglycemic potential of 6-(4-ethyl-5-mercapto-4H-1,2,4-triazol-3-yl)pyrimidine-2,4(1H,3H)-dione derivatives

Type 2 diabetes mellitus is one of the most prevalent metabolic diseases worldwide, characterized by chronic hyperglycemia and the development of severe complications. A key approach to its treatment involves the use of α-glucosidase inhibitors, which slow carbohydrate absorption in the intestine and thereby reduce postprandial hyperglycemia. In the search for new biologically active compounds, 1,2,4-triazole derivatives have garnered significant interest due to their broad spectrum of pharmacological properties, including hypoglycemic activity. The aim of this study is to evaluate the potential inhibitory activity of S-derivatives of 6-(4-ethyl-5-mercapto-4H-1,2,4-triazol-3-yl)pyrimidine-2,4(1H,3H)-diones against α-glucosidase and to assess their potential as hypoglycemic agents. To investigate the inhibitory activity of the studied compounds, molecular modeling (in silico analysis) was employed, specifically using the molecular docking method. The study was conducted using AutoDock Vina software, enabling the prediction of interactions between the synthesized 1,2,4-triazole derivatives and the active site of α-glucosidase. The obtained docking results were analyzed based on binding energy values, interaction configurations, and the presence of hydrogen bonds with key amino acid residues of the enzyme. Molecular modeling results revealed that S-derivatives of 6-(4-ethyl-5-mercapto-4H-1,2,4-triazol-3-yl)pyrimidine-2,4(1H,3H)-diones exhibit high affinity for the active site of α-glucosidase. The most promising compounds demonstrated binding energies ranging from -8.5 to -9.2 kcal/mol, which are comparable to or exceed the activity of known inhibitors of this enzyme. Interaction analysis indicated that key functional groups of the studied compounds form hydrogen and hydrophobic bonds with amino acid residues in the enzyme’s active site, suggesting potential stability of these complexes in biological environments. The findings highlight the potential of S-derivatives of 6-(4-ethyl-5-mercapto-4H-1,2,4-triazol-3-yl)pyrimidine-2,4(1H,3H)-diones as effective α-glucosidase inhibitors. Their high affinity for the enzyme’s active site, along with favorable interaction energy parameters, supports their further investigation as candidates for the development of new hypoglycemic drugs.