DAPY类化合物抑制野生型HIV-1活性的QSAR研究  

QSAR studies on diarypyrimidines as inhibiting activity of HIV-1 virus wildtype

作　　者：石春雨[1] 聂长明[1] 刘慧杰[1] 宁左云[1] 

机构地区：[1]南华大学化学化工学院,湖南衡阳421001

出　　处：《分子科学学报》2012年第1期66-71,共6页Journal of Molecular Science

基　　金：湖南省优秀博士学位论文基金资助项目(2008YBX01);湖南省科技计划项目资助(06FJ54104)

摘　　要：应用分子力学、半经验量子化学RM1方法优化了32个抗野生型HIV-1病毒毒株的二芳基嘧啶类(DAPYs)化合物分子结构,从分子构象模型中提取了多种参数并结合疏水性参数与指示性参数建立QSAR多元线性回归方程.回归方程显示:分子体积V的增大会降低其抑制活性,而左苯环与嘧啶环间二面角θ增大可以提高抑制活性.同时指示性参数I表明左苯环CN基团加入可以明显增加抑制活性,嘧啶环上R1位置苯基与硝基的加入可以极大降低抑制活性.Molecular mechanics and semi-empirical quantum RM1 methods were used to refine,optimize the geometry of 31 DAPY（diarylpyrimidine） derivatives and then extracted physicochemical properties parameters, molecular parameters,geometric parmeter from the geometric model along with combined indicator parameter to established the QSAR model for diarylpyrimidines against HIV-1 reverse tran- scriptase wild-type. Based on the multiple linear regression analysis, sorts of descriptors was invested and finally selected the dihedral （0）,molecular volume （V） and combined indicator parameters （I） to build a significant QSAR equation. It reveal that the hydrophobicity index iogP is actually not impor- tant as preciously reported in the prediction of inhibition activity of DAPYs. Decrease the volume,in- crease the dihedral between the left phenyl ring and pyrimidine ring can enhance the activity of inhibi- tion. The --CN group on the left phenyl ring is important for inhibiting activity. Ph,NO2 group at the R1 substitute can decrease the inhibiting activity rapidly.

关 键 词：HIV-1 疏水性参数 二芳基嘧啶类似物(DAPYs) QSAR 

分 类 号：O641[理学—物理化学]