目的 设计合成HIV-1病毒感染因子(Vif)抑制剂RN-18的衍生物并测试其抗HIV-1活性。方法 以RN-18为先导化合物,针对其两个支链及中间苯环设计合成衍生物,以p24含量来检测化合物抑制HIV-1的增殖活性,最后通过MTT法评价抗病毒效果较好化合物的细胞毒性。结果 共合成得到28个RN-18衍生物,结构经MS、NMR表征。活性测试表明,7个化合物抗HIV-1活性较RN-18更为显著,其中化合物26的活性提升了11倍以上,EC50值达到了21.8 μmol·L-1。结论 将RN-18的苯环替换为杂环可普遍提高抗HIV-1活性,为该类化合物的进一步优化指明了方向。
Abstract
OBJECTIVE To design and synthesize HIV-1 Vif inhibitor RN-18 derivatives and investigate their antiviral activities. METHODS RN-18 was used as the lead compound, and optimizations were carried out on the two side chains and the middle benzene ring. The anti-HIV-1 activities of the target compounds were analyzed by p24 assay, and the cytotoxicities of compounds with better activities were tested with MTT method. RESULTS Twenty-eight new derivatives were prepared, and their structures were characterized by MS and 1H-NMR. The activity test showed that the antiviral activities of seven compounds were obviously improved, and the activity of compound 26 was increased to be 11 times higher than that of RN-18, with an EC50 value of 21.8 μmol·L-1. CONCLUSION Replacing the middle benzene ring of RN-18 with heterocycles generally improves the anti-HIV-1 activity, which provides the basis for further study.
关键词
N-苯甲酰胺衍生物 /
病毒感染因子 /
抗艾滋病毒活性 /
抑制剂 /
构效关系
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Key words
N-benzamide derivatives /
Vif /
anti-HIV-1 activity /
inhibitor /
structure-activity relationship
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中图分类号：
R914
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参考文献
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脚注
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基金
国家自然科学基金项目资助(81660570)
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