新型HIV逆转录酶和整合酶双靶点抑制剂的虚拟筛选  

Virtual screening of novel dual inhibitors of HIV reverse transcriptase and integrase

作　　者：肖泽云[1] 李凯[1,2] 李爱秀 王晓辉[4] 刘勇庆[5] 

机构地区：[1]武警后勤学院基础部药物设计实验室,天津300309 [2]武警山西总队医院医学工程科,山西太原030006 [3]武警后勤学院天津市职业与环境危害防制重点实验室,天津300309 [4]武警后勤学院训练部教保处,天津300309 [5]武警后勤学院附属医院药剂科,天津300162

出　　处：《中国医药导报》2017年第27期4-7,20,共5页China Medical Herald

基　　金：国家自然科学基金资助项目(81241114)

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。Objective To create the pharmacophore of 3-OH HEPT derivatives of dual inhibitors against HIV non-nu cleoside 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 pharmaeophore of six features was created. 16 molecules which matched five out of the six features were hit by searching from texting database, and the detection rate was 100%. 229 compounds were hit when used the pharmacophore of six features and Lipinski＇s five rules to filter TCMD, which contained compounds that were known inhibitors of HIV. Conclusion The pharmacophore and the screening strategy lay a good foundation for further studies.

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 

分 类 号：R918[医药卫生—药学]