Search

The article presents the results of a study of the neurotoxicological profile of the new compound AB-19, acting on collagen glycation end products (AGE) and their receptors (RAGE), for the prevention and treatment of diabetes complications. The multi-test method «S. Irwin» was used. The test results were evaluated in parallel groups receiving the substance in doses starting with the average effective dose (ED50) and with a multiple increase by 5, 10, 20 and 50 times. It was found that the compound AB-19 in doses of 20, 100 and 200 mg / kg does not affect the functional and behavioral status of animals. However, with an increase to 400 mg / kg, typical manifestations of intoxication were observed: a decrease in muscle tone, hypothermia, sedation, tachypnea. As a result of the study, it was revealed that the neurotoxicological properties of the compound AB-19 are characterized by dose-dependent activity. A minimum toxic dose of 400 mg / kg ≤ Tdmin ≤ 1000 mg / kg was also indicated.

Inhibition of the dipeptidyl peptidase-4 (DPP4) enzyme activity and prevention of advanced glycation end (AGE) products formation represents a reliable approach to achieve control over hyperglycemia and the associated pathogenesis of diabetic vascular complications. In the frames of this research study, several triazolo- and pyrazolotriazines were synthesized and evaluated as inhibitors of AGE products formation, DPP4, glycogen phosphorylase and α-glucosidase activities, as well as AGE cross-link breakers. From the two considered classes of heterocyclic compounds, the pyrazolotriazines showed the highest potency as antiglycating agents and DPP4 inhibitors. Structure-activity relationships (SAR) for these compounds, which can be considered as potential drugs for the treatment of type 2 diabetes, were evaluated.