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

doi:10.3389/fchem.2021.639279

	Discovery of New alpha-Glucosidase Inhibitors: Structure-Based Virtual Screening and Biological Evaluation
	Liu, Shan-Kui 5; Hao, Haifang 5; Bian, Yuan 5; Ge, Yong-Xi 5; Lu, Shengyuan 5; Xie, Hong-Xu 5; Wang, Kai-Ming 5; Tao, Hongrui 2; Yuan, Chao 3; Zhang, Juan 5
刊名	FRONTIERS IN CHEMISTRY
	2021-03-08
卷号	9 页码:9
关键词	α -glycosidase virtual screening cytotoxicity type 2 diabetes molecular docking
ISSN号	2296-2646
DOI	10.3389/fchem.2021.639279
通讯作者	Zhang, Juan(bio_zhangj@ujn.edu.cn) ; Jiang, Cheng-Shi(bio_jiangcs@ujn.edu.cn) ; Zhu, Kongkai(bio_zhukk@ujn.edu.cn)
英文摘要	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.
资助项目	Major Science and Technology Innovation Project of Shandong Province[2019JZZY011116] ; National Natural Science Foundation of China[21672082] ; National Natural Science Foundation of China[81803438] ; Natural Science Foundation of Shandong Province[ZR2019YQ31] ; Natural Science Foundation of Shandong Province[ZR201910300056] ; Key Technology Research andDevelopment Programof Shandong[2019GSF108043] ; Science and Technology Project of University of Jinan[XKY2004]
WOS研究方向	Chemistry
语种	英语
出版者	FRONTIERS MEDIA SA
WOS记录号	WOS:000631068900001
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/295543]
专题	中国科学院上海药物研究所
通讯作者	Zhang, Juan; Jiang, Cheng-Shi; Zhu, Kongkai
作者单位	1.Qingdao Univ Sci & Technol, Coll Chem & Mol Engn, Shandong Key Lab Biochem Anal, Qingdao, Peoples R China 2.Chinese Acad Sci, Drug Discovery & Design Ctr, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai, Peoples R China 3.Zoucheng Adm Market Regulat, Zoucheng, Peoples R China 4.Lunan Pharmaceut Grp Corp, Linyi, Shandong, Peoples R China 5.Univ Jinan, Sch Biol Sci & Technol, Jinan, Peoples R China
推荐引用方式 GB/T 7714	Liu, Shan-Kui,Hao, Haifang,Bian, Yuan,et al. Discovery of New alpha-Glucosidase Inhibitors: Structure-Based Virtual Screening and Biological Evaluation[J]. FRONTIERS IN CHEMISTRY,2021,9:9.
APA	Liu, Shan-Kui.,Hao, Haifang.,Bian, Yuan.,Ge, Yong-Xi.,Lu, Shengyuan.,...&Zhu, Kongkai.(2021).Discovery of New alpha-Glucosidase Inhibitors: Structure-Based Virtual Screening and Biological Evaluation.FRONTIERS IN CHEMISTRY,9,9.
MLA	Liu, Shan-Kui,et al."Discovery of New alpha-Glucosidase Inhibitors: Structure-Based Virtual Screening and Biological Evaluation".FRONTIERS IN CHEMISTRY 9(2021):9.