Discovery of New α-Glucosidase Inhibitors: Structure-Based Virtual Screening and Biological Evaluation

alpha-Glycosidase inhibitors could inhibit the digestion of carbohydrates into glucose and promote glucose conversion, which have been used for the treatment of type 2 diabetes. In the present study, 52 candidates of alpha-glycosidase inhibitors were selected from commercial Specs compound library based on molecular docking-based virtual screening. Four different scaffold compounds (7, 22, 37, and 44) were identified as alpha-glycosidase inhibitors with IC50 values ranging from 9.99 to 35.19 mu M. All these four compounds exerted better inhibitory activities than the positive control (1-deoxynojirimycin, IC50 = 52.02 mu M). The fluorescence quenching study and kinetic analysis revealed that all these compounds directly bind to alpha-glycosidase and belonged to the noncompetitive alpha-glycosidase inhibitors. Then, the binding modes of these four compounds were carefully investigated. Significantly, these four compounds showed nontoxicity (IC50 > 100 mu M) toward the human normal hepatocyte cell line (LO2), which indicated the potential of developing into novel candidates for type 2 diabetes treatment.