Synthesis and biological evaluation of novel coumarin derivatives bearing sulfonamide moiety as potent α-glucosidase inhibitors

• Published in: Journal of the Iranian Chemical Society
• Main Author: Alsukor A.; Inayatsyah N.A.; Ridhwan M.J.M.; Kasim N.; Imran S.
• Format: Article
• Language: English
• Published: Springer Science and Business Media Deutschland GmbH 2024
• Online Access: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85212866917&doi=10.1007%2fs13738-024-03143-2&partnerID=40&md5=83dfeff9edd9acadcfed5f1428722a6f

Acarbose, miglitol and voglibose are α-glucosidase enzyme inhibitors that are clinically used to treat type-II diabetes mellitus. However, they are also associated with several adverse side effects. In this study, a series of sulfonamide-substituted coumarin was synthesised in a three-step reaction from precursor, 2-oxo-2H-chromene-3-carboxylic acid. The structure of all synthesised compounds was confirmed using NMR, FTIR and LCMS analysis and found to be in good agreement with the calculated values. Synthesised coumarin derivatives were screened for their in vitro α-glucosidase inhibitory activity. Besides compound 8, 15 compounds demonstrated good to excellent inhibitory activity with the IC50 values ranging from 40.6 to 2021 µM as compared to acarbose (IC50 = 3410 ± 1.54 µM). A structure–activity relationship was established to form correlation of the substituents effect with inhibitory activity. It was found that chlorine substituent played an important role in the activity compared to other halogen substituents. Derivatives showing inhibition activity were subjected to docking studies to identify the binding modes contributing towards the inhibition activity. © Iranian Chemical Society 2024.