Design, synthesis and biological evaluation of indole derivatives as Vif inhibitors

CORC > 昆明动物研究所 > 昆明动物研究所 > 动物模型与人类重大疾病机理重点实验室

	Design, synthesis and biological evaluation of indole derivatives as Vif inhibitors
	Li R1; Hou XY 1; Yan GY 1; Pu CL 1; Luo RH 2; Luo J 1; Zheng YT2; Zhang MQ 1
刊名	Bioorganic & Medicinal Chemistry Letters
	2017
卷号	期号:页码:Epub ahead of print
关键词	Apobec3g Degradation Fbvs Indole Derivatives Vif Inhibitor
其他题名	zhengyt@mail.kiz.ac.cn ;lirui@scu.edu.cn
英文摘要	The crystal structure of viral infectivity factor (Vif) was reported recently, which makes it possible to design new inhibitors against Vif by structure-based drug design. Through analysis of the protein surface of Vif, the C2 pocket located in the N-terminal was found, which is suit for developing small molecular inhibitors. Then, in our article, fragment-based virtual screening (FBVS) was conducted and a series of fragments was obtained, among which, Zif-1 bearing indole scaffold and pyridine ring can form H-bonds with Tyr148 and Ile155. Subsequently, 19 derivatives of Zif-1 were synthesized. Through the immune-fluorescence staining and Western blot assays, Zif-15 shows potent activity in inhibiting Vif-mediated A3G degradation. Further docking experiment shows that Zif-15 form H-bond interactions with residues His139, Tyr148 and Ile155. Therefore, Zif-15 is a promising lead compound against Vif that can be used to treat AIDS.
语种	英语
资助机构	We also thank the support of the National Natural Science Foundation of China (81472780, 81102483) and the National Key Program of China during the 12th Five-Year Plan Per- iod (Grant 2012ZX09103101-022). ; We also thank the support of the National Natural Science Foundation of China (81472780, 81102483) and the National Key Program of China during the 12th Five-Year Plan Per- iod (Grant 2012ZX09103101-022).
内容类型	期刊论文
源URL	[http://159.226.149.26:8080/handle/152453/12008]
专题	昆明动物研究所_动物模型与人类重大疾病机理重点实验室昆明动物研究所_分子免疫药理学
作者单位	1.Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041 Sichuan, PR China 2.Key Laboratory of Bioactive Peptides of Yunnan Province/Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China
推荐引用方式 GB/T 7714	Li R,Hou XY,Yan GY,et al. Design, synthesis and biological evaluation of indole derivatives as Vif inhibitors[J]. Bioorganic & Medicinal Chemistry Letters,2017,(*):Epub ahead of print.
APA	Li R.,Hou XY.,Yan GY.,Pu CL.,Luo RH.,...&Zhang MQ.(2017).Design, synthesis and biological evaluation of indole derivatives as Vif inhibitors.Bioorganic & Medicinal Chemistry Letters,(*),Epub ahead of print.
MLA	Li R,et al."Design, synthesis and biological evaluation of indole derivatives as Vif inhibitors".Bioorganic & Medicinal Chemistry Letters .*(2017):Epub ahead of print.