State Key Laboratory of Functions and Applications of Medicinal Plants & Tissue Engineering and Stem Cell Research Center, Guizhou Medical University, Guiyang 550004, Guizhou, PR China.
Engineering Research Center for the Development and Application of Ethnic Medicine and TCM, Ministry of Education Guizhou Medical University, Guiyang, Guizhou, PR China; School of Pharmacy, Guizhou Medical University, Guian New District, Guizhou, PR China.
Bioorg Med Chem Lett. 2019 Dec 15;29(24):126638. doi: 10.1016/j.bmcl.2019.126638. Epub 2019 Aug 28.
Viral infectivity factor (Vif) is one of the accessory protein of human immunodeficiency virus type I (HIV-1) that inhibits host defense factor, APOBEC3G (A3G), mediated viral cDNA hypermutations. Previous work developed a novel Vif inhibitor 2-amino-N-(2-methoxyphenyl)-6-((4-nitrophenyl)thio)benzamide (1) with strong antiviral activity. Through optimizations on the two side branches, a series of compound 1 derivatives (2-18) were designed, synthesized and tested in vitro for their antiviral activities. The biological results showed that compound 5 and 16 inhibited the virus replication efficiently with EC values of 9.81 and 4.62 μM. Meanwhile, low cytotoxicities on H9 cells were observed for the generated compounds by the MTT assay. The structure-activity relationship of compound 1 was preliminarily clarified, which gave rise to the development of more potent Vif inhibitors.
病毒感染性因子（Vif）是人类免疫缺陷病毒 I 型（HIV-1）的辅助蛋白之一，可抑制宿主防御因子 APOBEC3G（A3G）介导的病毒 cDNA 超突变。先前的工作开发了一种新型的 Vif 抑制剂 2-氨基-N-（2-甲氧基苯基）-6-（（4-硝基苯基）硫）苯甲酰胺（1），具有很强的抗病毒活性。通过对两个侧链分支进行优化，设计、合成了一系列化合物 1 衍生物（2-18），并对其进行了体外抗病毒活性测试。生物实验结果表明，化合物 5 和 16 对病毒复制的抑制作用较强，EC 值分别为 9.81 和 4.62 μM。同时，通过 MTT 检测，这些生成的化合物对 H9 细胞的细胞毒性较低。初步阐明了化合物 1 的构效关系，为开发更有效的 Vif 抑制剂提供了依据。
