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

• Published in: Future Medicinal Chemistry
• Main Author: Taha M.; Rahim F.; Hayat S.; Chigurupati S.; Khan K.M.; Imran S.; Ali Shah S.A.; Uddin N.; Felemban S.G.; Venugopal V.
• Format: Article
• Language: English
• Published: Newlands Press Ltd 2023
• Online Access: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85152169411&doi=10.4155%2ffmc-2022-0306&partnerID=40&md5=e9c0aac096a6a177f277d68333c893ec

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. © 2023 Newlands Press.