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Synthesis, biological evaluation and molecular docking study of N-(2-methoxyphenyl)-6-((4-nitrophenyl)sulfonyl)benzamide derivatives as potent HIV-1 Vif antagonists.

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资源类型：
Pubmed体系：
作者：
Meng Zhou[a,c,d] * ; Rong-Hua Luo[b] * ; Xue-Yan Hou[a] * ; Rui-Rui Wang[b] ; Guo-Yi Yan[a] ; Huan Chen[b] ; Rong-Hong Zhang[e] ; Jian-You Shi[a] ; Yong-Tang Zheng[b] ; Rui Li[a] ; Yu-Quan Wei[a] ;
机构： [a]State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu, Sichuan 610041, PR China [b]Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, PR China [c]Engineering Research Center for the Development and Application of Ethnic Medicine and TCM, Ministry of Education, Guizhou Medical University, Guiyang 550004, Guizhou, PR China [d]National Engineering Research Center of Miao‘s Medicines, Guizhou Medical University, Guiyang 550004, Guizhou, PR China [e]Tissue Engineering and Stem Cell Research Center, Guizhou Medical University, Guiyang 550004, Guizhou, PR China
出处：
DOI： 10.1016/j.ejmech.2017.01.010
ISSN：

关键词： Vif antagonists Vif mediated A3G degradation Nonpermissive Antiviral activity

摘要：
Viral infectivity factor (Vif) is protective against APOBEC3G (A3G)-mediated viral cDNA hypermutations, and development of molecules that inhibit Vif mediated A3G degradation is a novel strategy for blocking HIV-1 replication. Through optimizations of the central ring of N-(2-methoxyphenyl)-2-((4-nitrophenyl)thio)benzamide (RN-18), we found a potent compound 12c with EC50 value of 1.54 μM, enhancing the antiviral activity more than 150-fold compared with RN-18 in nonpermissive H9 cells. 12c protected A3G from degradation by inhibiting Vif function. Besides, 12c suppressed different HIV-1 clinical strains (HIV-1KM018, HIV-1TC-1 and HIV-1WAN) and drug-resistant strains (NRTI, NNRTI, PI, and FI) with relatively high activities. Amidation of 12c with glycine gave a prodrug 13a, improving the water solubility about 2600-fold compared with 12c. Moreover, 13a inhibited the virus replication efficiently with an EC50 value of 0.228 μM. These results suggested that the prodrug 13a is a promising candidate agent for the treatment of AIDS. Copyright © 2017. Published by Elsevier Masson SAS.

基金：
This study was support by the National Key Program of China during the 12th Five-Year Plan Period (Grant 2012ZX09103101-022, 2012ZX10001-006), the National Natural Science Foundation of China (81102483, 81472780), and the Innovation Team of Natural Science Foundation of Department of Education of Guizhou Province (No. QJHRCTDZ [2015] 57). We thank LetPub (www.letpub.com) for its linguistic assistance during the preparation of this manuscript.
语种：
外文
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中科院(CAS)分区：
出版当年[2017]版：
大类 | 2 区 化学
小类 | 1 区 药物化学
最新[2023]版：
大类 | 2 区 医学
小类 | 1 区 药物化学
第一作者：
第一作者机构： [a]State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu, Sichuan 610041, PR China [c]Engineering Research Center for the Development and Application of Ethnic Medicine and TCM, Ministry of Education, Guizhou Medical University, Guiyang 550004, Guizhou, PR China [d]National Engineering Research Center of Miao‘s Medicines, Guizhou Medical University, Guiyang 550004, Guizhou, PR China
共同第一作者：
通讯作者：
推荐引用方式(GB/T 7714)：
Meng Zhou,Rong-Hua Luo,Xue-Yan Hou,et al.Synthesis, biological evaluation and molecular docking study of N-(2-methoxyphenyl)-6-((4-nitrophenyl)sulfonyl)benzamide derivatives as potent HIV-1 Vif antagonists.[J].European journal of medicinal chemistry.2017,129:310-324.doi:10.1016/j.ejmech.2017.01.010.
APA：
Meng Zhou,Rong-Hua Luo,Xue-Yan Hou,Rui-Rui Wang,Guo-Yi Yan...&Yu-Quan Wei.(2017).Synthesis, biological evaluation and molecular docking study of N-(2-methoxyphenyl)-6-((4-nitrophenyl)sulfonyl)benzamide derivatives as potent HIV-1 Vif antagonists..European journal of medicinal chemistry,129,
MLA：
Meng Zhou,et al."Synthesis, biological evaluation and molecular docking study of N-(2-methoxyphenyl)-6-((4-nitrophenyl)sulfonyl)benzamide derivatives as potent HIV-1 Vif antagonists.".European journal of medicinal chemistry 129.(2017):310-324

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