Design, synthesis and biological evaluation of vincamine derivatives as potential pancreatic beta-cells protective agents for the treatment of type 2 diabetes mellitus

doi:10.1016/j.ejmech.2019.111976

	Design, synthesis and biological evaluation of vincamine derivatives as potential pancreatic beta-cells protective agents for the treatment of type 2 diabetes mellitus
	Wang, Junwei 1; Lv, Xue 2; Xu, Jiawen 1; Liu, Xinpeng 1; Du, Te 2,3; Sun, Guanglong 2,3; Chen, Jing 2,3; Shen, Xu 1; Wang, Jiaying 1; Hu, Lihong 1,2,3
刊名	EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
	2020-02-15
卷号	188 页码:17
关键词	Type 2 diabetes mellitus Pancreatic beta-cells protective agents Vincamine derivatives Structural modifications Structure-activity relationships
ISSN号	0223-5234
DOI	10.1016/j.ejmech.2019.111976
通讯作者	Wang, Jiaying(wangjy@njucm.edu.cn) ; Hu, Lihong(lhhu@njucm.edu.cn)
英文摘要	A series of vincamine derivatives were designed, synthesized and evaluated as pancreatic beta-cells protective agents for type 2 diabetes mellitus. Most of the compounds displayed potent pancreatic beta-cells protective activities and five derivatives were found to exhibit 20-50-fold higher activities than vincamine. Especially for compounds Vin-C01 and Vin-F03, exhibited a remarkable EC50 value of 0.22 mu NI and 0.27 mu M, respectively. Their pancreatic beta-cells protective activities increased approximately 2 times than vincamine. In cell viability assay, compounds Vin-001 and Vin-F03 could effectively promote beta-cell survival and protect beta-cells from STZ-induced apoptosis. Further cellular mechanism of action studies demonstrated that their potent protective activities were achieved by regulating IRS2/Pl3K/Akt signaling pathway. The present study evidently showed that compounds Vin-C01 and Vin-F03 were two more potent pancreatic beta-cells protective agents compared to vincamine and might serve as promising lead candidates for the treatment of type 2 diabetes mellitus. (C) 2019 Elsevier Masson SAS. All rights reserved.
资助项目	National Natural Science Foundation of China[81773596] ; Natural Science Foundation of Jiangsu Province[BK20180826] ; Natural science foundation of Jiangsu Higher Education Institutions[17KJA360004] ; Natural science foundation of Jiangsu Higher Education Institutions[18KJB350008] ; Program for Outstanding Scientific and Technological Innovation Team of Jiangsu Higher Education Institutions ; Priority Academic Program Development of Jiangsu Higher Education Institutions
WOS关键词	APOPTOSIS
WOS研究方向	Pharmacology & Pharmacy
语种	英语
出版者	ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
WOS记录号	WOS:000515428100018
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/281464]
专题	中国科学院上海药物研究所
通讯作者	Wang, Jiaying; Hu, Lihong
作者单位	1.Nanjing Univ Chinese Med, Stake Key Lab Cultivat Base TCM Qual & Efficacy, Jiangsu Collaborat Innovat Ctr Chinese Med Resour, Jiangsu Key Lab Funct Subst Chinese Med,Sch Pharm, Nanjing 210023, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
推荐引用方式 GB/T 7714	Wang, Junwei,Lv, Xue,Xu, Jiawen,et al. Design, synthesis and biological evaluation of vincamine derivatives as potential pancreatic beta-cells protective agents for the treatment of type 2 diabetes mellitus[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2020,188:17.
APA	Wang, Junwei.,Lv, Xue.,Xu, Jiawen.,Liu, Xinpeng.,Du, Te.,...&Hu, Lihong.(2020).Design, synthesis and biological evaluation of vincamine derivatives as potential pancreatic beta-cells protective agents for the treatment of type 2 diabetes mellitus.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,188,17.
MLA	Wang, Junwei,et al."Design, synthesis and biological evaluation of vincamine derivatives as potential pancreatic beta-cells protective agents for the treatment of type 2 diabetes mellitus".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 188(2020):17.