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

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 IC50 value of 53.0 ± 7.7 μM, is more competitive compared with the commercially available drug acarbose (IC50 = 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. [ABSTRACT FROM AUTHOR]