Thiazole-benzamide derivatives as α-glucosidase inhibitors: Synthesis, kinetics study, molecular docking, and in vivo evaluation

Abstract

In this study, a series of thiazole-benzamide derivatives (6a-6o) was obtained by molecular hybridization and screened for their inhibitory study towards the α-glucosidase activity. The results showed that all compounds (6a-6o) showed α-glucosidase (from S. cerevisiae) inhibitory activity (IC50 = 12.18 ± 0.08 - 79.34 ± 1.30 μM) by comparison with standard acarbose (IC50 = 774.69 ± 11.65 μM). A study on the kinetics of compound 6c showed a competitive mode against α-glucosidase. In addition, the changes in fluorescence intensity, secondary structure, and possible binding sites in the interaction between 6c and α-glucosidase were studied using fluorescence spectrometry, circular dichroism, and molecular docking, respectively. Furthermore, in vivo experiment indicated that 6c can reduce the rise of blood sugar levels in the sucrose loading experiment. Moreover, compound 6c had low cytotoxic activity toward the human normal HEK 293 cell line.