肖泽云 李凯 李爱秀

    [摘要] 目的 构建3-OH HEPT类针对HIV逆转录酶非核苷类抑制剂作用靶点和整合酶的双靶点抑制剂[RT(NNRTI)/IN]药效团模型，对中药化学数据库(TCMD)进行搜索，寻找潜在的新型HIV双靶点抑制剂。 方法 从已知的3-OH HEPT类HIVRT(NNRTI)/IN双靶点抑制剂出发，构建药效团模型，基于药效团模型和Lipinski五规则对TCMD进行筛选，发现新的抗HIV双靶点抑制剂。 结果 构建的药效团模型包括6个药效特征基团，以符合6个药效特征基团中任意5个为条件，在测试集数据库中验证性搜索命中全部16个化合物，检出率达到了100%。利用所建的六点药效团模型和Lipinski五规则对TCMD筛选，得到符合条件的化合物229个，其中包含已知的抗HIV活性化合物。 结论 建立的药效团模型和筛选策略为后续研究打下了较好的基础。

    [关键词] 3-OH HEPT衍生物；RT(NNRTI)/IN；双靶点抑制剂；药效团模型；虚拟筛选

    [中图分类号] R918 [文献标识码] A [文章编号] 1673-7210(2017)09(c)-0004-05

    [Abstract] Objective To create the pharmacophore of 3-OH HEPT derivatives of dual inhibitors against HIV non-nucleoside reverse transcriptase inhibit or binding pocket and integrase [RT(NNRTI)/IN]， filter traditional Chinese medicine database (TCMD) with the pharmacophore， and find novel dual inhibitors of HIV. Methods Based on the known 3-OH HEPT derivatives against HIV RT(NNRTI)/IN， the pharmacophore was created. TCMD was filtered with the pharmacophore and Lipinski's five rules. Results The pharmacophore of six features was created. 16 molecules which matched five out of the six features were hit by searching from texting database ......