Discovery of N‐(phenylsulfonyl)thiazole‐2‐carboxamides as potent α‐glucosidase inhibitors

Abstract In a search for novel nonsugar α ‐glucosidase inhibitors for diabetes treatment, a series of N ‐(phenylsulfonyl)thiazole‐2‐carboxamide derivatives were designed and synthesized, the α ‐glucosidase inhibitory activities were then evaluated. Several compounds with promising α ‐glucosidase inhibitory effects were identified. Among these, compound W24 which shows low cytotoxicity and good α ‐glucosidase inhibitory activity with an IC 50 value of 53.0 ± 7.7 μM, is more competitive compared with the commercially available drug acarbose (IC 50 = 228.3 ± 9.2 μM). W24 was identified as a promising candidate in the development of α ‐glucosidase inhibitors. Molecular docking studies and molecular dynamics simulation were also performed to reveal the binding pattern of the active compound to α ‐glucosidase, and the binding free energy of the best compound W24 was 36.3403 ± 3.91 kcal/mol.