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

Aim: To synthesize pyrrolopyridine-based thiazolotriazoles as a novel class of alpha-amylase and alpha-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 alpha-amylase and alpha-glucosidase ranging 17.65-70.7 mu M and 18.15-71.97 mu M, respectively, compared with the reference drug, acarbose (11.98 mu M and 12.79 mu M). Analog 3 was the most potent among the synthesized analogs, having alpha-amylase and alpha-glucosidase inhibitory activity at 17.65 and 18.15 mu M, 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.

Automated summary

Aim: The aim of this study was to synthesize pyrrolopyridine-based thiazolotriazoles as a novel class of alpha-amylase and alpha-glucosidase inhibitors and determine their enzymatic kinetics. Methodology: Pyrrolopyridine-based thiazolotriazole analogs (1-24) were synthesized and characterized through various spectroscopic techniques. Results: The synthesized analogs exhibited significant inhibitory potential against alpha-amylase and alpha-glucosidase, with analog 3 showing the highest inhibitory activity. The structure-activity relationship and binding modes of interactions were confirmed through docking and enzymatic kinetics studies. The compounds (1-24) showed no cytotoxicity against the 3T3 mouse fibroblast cell line.