New pyrrolopyridine-based thiazolotriazolesas diabetics inhibitors: enzymatic kinetics andin silico study.

Abstract

Aim: To synthesizepyrrolopyridine-based thiazolotriazoles as a novel class ofα-amylase and α-glucosidase inhibitors and to determine their enzymatic kinetics. Methodology: Pyrrolopyridine-based thiazolotriazole analogs (1-24) were synthesized and characterized through proton nuclear magnetic resonance, carbon-13nuclear magnetic resonance andhigh-resolution electron ionization mass spectrometry. Results: All synthesized analogs displayed good inhibitory potential of α-amylase and α-glucosidase ranging 17.65-70.7μM and 18.15-71.97μM, respectively, compared with the reference drug, acarbose (11.98μM and 12.79μM). Analog 3 was the most potent among thesynthesized analogs, having α-amylase and α-glucosidase inhibitory activity at17.65 and 18.15μM, respectively. Thestructure-activity relationship and binding modes of interactions between selected analogs were confirmed via docking and enzymatic kinetics studies. The compounds (1-24) were tested for cytotoxicity against the3T3 mouse fibroblast cell line and wereobserved to benontoxic.