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

In a search for novel nonsugar alpha-glucosidase inhibitors for diabetes treatment, a series of N-(phenylsulfonyl)thiazole-2-carboxamide derivatives were designed and synthesized, the alpha-glucosidase inhibitory activities were then evaluated. Several compounds with promising alpha-glucosidase inhibitory effects were identified. Among these, compound W24 which shows low cytotoxicity and good alpha-glucosidase inhibitory activity with an IC50 value of 53.0 +/- 7.7 mu M, is more competitive compared with the commercially available drug acarbose (IC50 = 228.3 +/- 9.2 mu M). W24 was identified as a promising candidate in the development of alpha-glucosidase inhibitors. Molecular docking studies and molecular dynamics simulation were also performed to reveal the binding pattern of the active compound to alpha-glucosidase, and the binding free energy of the best compound W24 was 36.3403 +/- 3.91 kcal/mol.