- Design, synthesis and biological evaluation of indole derivatives as Vif inhibitors
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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.
- Pu, Chunlan,Luo, Rong-Hua,Zhang, Mengqi,Hou, Xueyan,Yan, Guoyi,Luo, Jiang,Zheng, Yong-Tang,Li, Rui
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supporting information
p. 4150 - 4155
(2017/08/22)
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- Identification of a novel class of autotaxin inhibitors through cross-screening
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Three novel series were generated in order to mimic the pharmacophoric features displayed by lead compound AM095, a lysophosphatidic acid (LPA1) receptor antagonist. Biological evaluation of this array of putative LPA1 antagonists le
- Castagna, Diana,Duffy, Emma L.,Semaan, Dima,Young, Louise C.,Pritchard, John M.,Macdonald, Simon J. F.,Budd, David C.,Jamieson, Craig,Watson, Allan J. B.
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p. 1149 - 1155
(2015/06/25)
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