紫杉醇衍生物的三维定量构效关系研究

Studies on the Quantitative Structure activity Relationships of Paclitaxel Analogues

利用比较分子力场分析 (Co MFA)方法对 98个紫杉醇衍生物的三维定量构效关系 (3D-QSAR)进行了分析 ,发现影响其活性的立体能与静电能之比为 61 .6/38.4 .进一步分析表明 ,C-1 3侧链基团的改变对其活性影响较大 ,尤其是 2 -OH对保持活性是至关重要的 ;而母环其它位置取代基的改变对活性影响较小 .该模型交叉验证 r2cv=0 .71 4 ,非交叉验证 r2 =0 .90 1 ;以此模型对验证组 1 0个化合物活性进行预测 ,r2pred=0 .81 2 ,表明模型具有很好的预测能力 。

A series of 98 paclitaxel analogues were investigated using the comparative molecular field analysis(CoMFA) and a high predictive 3D QSAR model with a significant cross validated r 2 cv , conventional r 2, and predictive r 2 pred. equaling to 0.714, 0.901, 0.812, respectively was obtained. It revealed that the changes of the C 13 side chain groups, especially 2 OH, affected the activity significantly and others did less relatively. It also showed that the model was significant for the research and development of novel paclitaxel analogues to reduce the blind flight during drug designing.