Design, synthesis and anti-diabetic activity of novel 1, 2, 3-triazole-5-carboximidamide derivatives as dipeptidyl peptidase-4 inhibitors

• Published in: Journal of molecular structure Vol. 1221; p. 128745
• Main Authors: Dastjerdi, Hossein Fasihi, Naderi, Nima, Nematpour, Manijeh, Rezaee, Elham, Mahboubi-Rabbani, Mohammad, Ebrahimi, Melika, Hosseinipoor, Samaneh, Hosseini, Omid, Tabatabai, Sayyed Abbas
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 05.12.2020
• Subjects: 1,2,3-Triazole-5-carboximidamide; Biological study; Diabetes; Dipeptidyl peptidase 4; Inhibitor; Dipeptidyl peptidase 4; Inhibitor; Diabetes; 1,2,3-Triazole-5-carboximidamide; Biological study
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2020.128745

The inhibitors of the enzyme dipeptidyl peptidase type 4 (DPP-4), as a potent stimulator of insulin secretion and an inhibitor of glucagon secretion from the pancreas, have been considered as promising agents for the treatment of type 2 diabetes mellitus. In this study, a novel series of 1, 2, 3-triazole-5-carboximidamide derivatives were designed, synthesized, and inhibitory activity evaluated against the DPP-4 enzyme. All of the compounds represented inhibitory activity, and among them, compounds 6a, 6b, and 6c showed desirable inhibitory activity of DPP-4 with IC50 values of 14.75 nM, 6.75 nM, and 6.57 nM, respectively. Compound 6a with a dose of 10 mg/kg showed glucose tolerance enhancement during OGTT in NMRI mice. Moreover, chronic treatment of Wistar rats for 14 days with compound 6a showed a significant decrease in blood glucose levels of diabetic rats, which was similar to sitagliptin as a standard. •Novel triazole derivatives against DPP4 enzyme were investigated.•Some compounds had inhibitory activity against DPP-4 enzyme in nanomolar range.•Compound 6a was orally active in OGTT and could decrease blood glucose levels of diabetic rats.