AUTHOR=Liu Shan-Kui , Hao Haifang , Bian Yuan , Ge Yong-Xi , Lu Shengyuan , Xie Hong-Xu , Wang Kai-Ming , Tao Hongrui , Yuan Chao , Zhang Juan , Zhang Jie , Jiang Cheng-Shi , Zhu Kongkai TITLE=Discovery of New α-Glucosidase Inhibitors: Structure-Based Virtual Screening and Biological Evaluation JOURNAL=Frontiers in Chemistry VOLUME=9 YEAR=2021 URL=https://www.frontiersin.org/journals/chemistry/articles/10.3389/fchem.2021.639279 DOI=10.3389/fchem.2021.639279 ISSN=2296-2646 ABSTRACT=

α-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 α-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 α-glycosidase inhibitors with IC50 values ranging from 9.99 to 35.19 μM. All these four compounds exerted better inhibitory activities than the positive control (1-deoxynojirimycin, IC50 = 52.02 μM). The fluorescence quenching study and kinetic analysis revealed that all these compounds directly bind to α-glycosidase and belonged to the noncompetitive α-glycosidase inhibitors. Then, the binding modes of these four compounds were carefully investigated. Significantly, these four compounds showed nontoxicity (IC50 > 100 μM) toward the human normal hepatocyte cell line (LO2), which indicated the potential of developing into novel candidates for type 2 diabetes treatment.