Journal
FRONTIERS IN CHEMISTRY
Volume 9, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fchem.2021.639279
Keywords
α -glycosidase; virtual screening; cytotoxicity; type 2 diabetes; molecular docking
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Funding
- Major Science and Technology Innovation Project of Shandong Province [2019JZZY011116]
- National Natural Science Foundation of China [21672082, 81803438]
- Natural Science Foundation of Shandong Province [ZR2019YQ31, ZR201910300056]
- Key Technology Research andDevelopment Programof Shandong [2019GSF108043]
- Science and Technology Project of University of Jinan [XKY2004]
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In this study, 52 candidates of alpha-glycosidase inhibitors were screened from a commercial compound library, with 4 identified compounds showing promising inhibitory activities and noncompetitive binding modes. These compounds exhibited low toxicity in human cells, indicating their potential as novel treatments for type 2 diabetes.
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.
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