New pyrrolopyridine-based thiazolotriazoles as diabetics inhibitors: enzymatic kinetics and in silico study.

ABSTRACT

Aim: To synthesize pyrrolopyridine-based thiazolotriazoles as a novel class of α-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-13 nuclear magnetic resonance and high-resolution electron ionization mass spectrometry. Results: All synthesized analogs displayed good inhibitory potential of α-amylase and α-glucosidase ranging 17.65-70.7 µM and 18.15-71.97 µM, respectively, compared with the reference drug, acarbose (11.98 µM and 12.79 µM). Analog 3 was the most potent among the synthesized analogs, having α-amylase and α-glucosidase inhibitory activity at 17.65 and 18.15 µM, respectively. The structure-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 the 3T3 mouse fibroblast cell line and were observed to be nontoxic.