Discovery of New alpha-Glucosidase Inhibitors: Structure-Based Virtual Screening and Biological Evaluation | |
Liu, Shan-Kui5; Hao, Haifang5; Bian, Yuan5; Ge, Yong-Xi5; Lu, Shengyuan5; Xie, Hong-Xu5; Wang, Kai-Ming5; Tao, Hongrui2; Yuan, Chao3; Zhang, Juan5 | |
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. |
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