Synthesis, biological evaluation and molecular docking study of N-(2-methoxyphenyl)-6-((4-nitrophenyl)sulfonyl)benzamide derivatives as potent HIV-1 Vif antagonists
文献类型：期刊论文
| 作者 | Zhou M1,3,4; Luo RH2; Chen H2; Zhang RH5; Shi JY1; Zheng YT[*]2; Li R[*]1; Wei YQ1; Hou XY1; Wang RR2 |
| 刊名 | European Journal of Medicinal Chemistry
 |
| 出版日期 | 2017 |
| 卷号 | 129期号:X页码:310-324 |
| 关键词 | Antiviral activity Nonpermissive Vif antagonists Vif mediated A3G degradation |
| 通讯作者 | zhengyt@mail.kiz.ac.cn ; lirui@scu.edu.cn |
| 英文摘要 | 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 EC50value of 0.228 μM. These results suggested that the prodrug 13a is a promising candidate agent for the treatment of AIDS. |
| 资助信息 | This study was support by the National Key Program of China during the 12th Five-Year Plan Period (Grant 2012ZX09103101-022, 2012ZX10001-006), the Na- tional 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). |
| 收录类别 | SCI |
| 语种 | 英语 |
| 源URL | [http://159.226.149.26:8080/handle/152453/10908]  |
| 专题 | 昆明动物研究所_分子免疫药理学 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 |
| 作者单位 | 1.State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu, Sichuan 610041, PR China 2.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 3.Engineering Research Center for the Development and Application of Ethnic Medicine and TCM, Ministry of Education, Guizhou Medical University, Guiyang 550004, Guizhou, PR China 4.National Engineering Research Center of Miao‘s Medicines, Guizhou Medical University, Guiyang 550004, Guizhou, PR China 5.Tissue Engineering and Stem Cell Research Center, Guizhou Medical University, Guiyang 550004, Guizhou, PR China |
| 推荐引用方式 GB/T 7714 | Zhou M,Luo RH,Chen H,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(X):310-324. |
| APA | Zhou M.,Luo RH.,Chen H.,Zhang RH.,Shi JY.,...&Yan GY.(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(X),310-324. |
| MLA | Zhou M,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.X(2017):310-324. |
入库方式： OAI收割
来源：昆明动物研究所
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