Hypoglycemic activity of new S-derivatives of 6-(5-mercapto-4-methyl-4H-1,2,4-triazol-3-yl)pyrimidine-2,4(1H,3H)-dione.

A fundamental aspect of the pathophysiology of type 2 diabetes is the progressive decline in the body's response to prandial insulin, particularly in the early stages of the disease. The early-phase insulin response is significantly impaired, playing a key role in accelerating endogenous glucose production. In type 2 diabetes, endogenous glucose production persists despite prandial glucose intake. Combined with a persistent relative deficiency in insulin secretion, this leads to a predisposition to postprandial hyperglycemia.

1,2,4-Triazole is a structural motif frequently explored in the development of new compounds with potential therapeutic applications, particularly for diabetes mellitus and other metabolic disorders. These compounds can modulate enzymes involved in glucose metabolism, including AMP-activated protein kinase (AMPK).

The potential hypoglycemic activity of the new compound was evaluated by measuring changes in blood glucose levels in animals after a single administration. Male Wistar rats (180–200 g) were used as test subjects and were housed under standard vivarium conditions. The animals were divided into two groups of six (n = 6). The control group received a third-generation sulfonylurea derivative, glimepiride (4 mg/kg), a structurally related hypoglycemic drug. The test group received the experimental compound orally via gavage, either as an aqueous solution or as a finely dispersed aqueous emulsion stabilized with Tween-80. Blood samples were collected from the tail vein before administration and at 2, 4, 6, and 8 hours post-administration.

Conclusions. The study results demonstrated that 2-((5-(2,6-dioxo-1,2,3,6-tetrahydropyrimidin-4-yl)-4-ethyl-4H-1,2,4-triazol-3-yl)thio)acetamide exhibits 1.5 times greater hypoglycemic activity than glimepiride. Molecular docking analysis confirmed the compound's high affinity for the α-glucosidase enzyme (PDB ID: 2ZE0).