HIV-1逆转录酶抑制剂的3D-QSAR研究及分子设计  

3D-QSAR and Molecular Docking Studies on Diarylaniline Derivatives of HIV-1 Reverse Transcriptase

作　　者：仝建波[1] 占培 吴英纪 

机构地区：[1]陕西科技大学化学与化工学院,陕西西安710021

出　　处：《分析测试学报》2016年第11期1397-1402,共6页Journal of Instrumental Analysis

基　　金：国家自然科学基金(21475081);陕西省自然科学基础研究计划(2015JM2057);陕西科技大学研究生创新基金

摘　　要：采用Topomer Co MFA方法对24个二芳基苯胺衍生物进行三维定量构效关系研究,建立了3DQSAR模型,所得优化模型的非交叉相关系数、交互验证系数以及外部验证的复相关系数分别为0.928,0.654和0.940,结果表明该模型具有良好的稳定性和预测能力。采用分子对接技术对药物与受体的作用机制进行了研究,结果显示,药物与HIV-1逆转录酶的LYS172,GLU138,LYS101等位点作用明显。运用这些信息进行分子设计,在理论上获得了一些具有较高活性的新的二芳基苯胺类抗艾滋病药物,该QSAR的研究结果可为新药合成提供理论参考。Topomer CoMFA was used to build a three-dimensional quantitative structure -activity relationship （ 3 D - QSAR） model for 24 diarylaniline derivatives in this paper. The coefficient of cross validation, the coefficient of non-cross validation and external validation were 0. 654, 0. 928 and 0. 940, respectively. The result showed that this model had a good stability and a predictive ability. By using molecular docking, the action mechanism of drug and acceptor was studied, and the results showed that the drug functions obviously with LYS172, GLU138, LYS101 sites of HIV - 1 reverse transcriptase. Based on the above informations, three new molecules of diarylaniline derivatives with high activity were theoretically designed, and the QSAR results could offer an atheoretical reference for the pharmaceutical synthesis.

关 键 词：三维定量构效关系 易位体比较分子场 分子对接 分子设计 二芳基苯胺衍生物 

分 类 号：O629.8[理学—有机化学] TQ460.72[理学—化学]