拓扑异构酶Ⅰ抑制剂高喜树碱类化合物的三维定量构效关系研究

针对拓扑异构酶Ⅰ抑制剂高喜树碱类化合物,采用比较分子力场分析(CoMFA)和比较分子相似性指数分析(CoMSIA)的方法对其进行三维定量构效关系的研究.构建CoMFA模型其q2=0.706,最佳主成分数n=6,非交叉验证系数r2=0.966,标准差S=0.277,F=117.613,立体场和静电场的贡献值分别为0.62和0.38.构建CoMSIA模型其q2=0.696,最佳主成分数n=7,非交叉验证系数r2=0.956,标准差S=0.320,F=74.374,其疏水场和立体场的贡献分别为0.75和0.25.结果显示疏水场和立体场对化合物的活性有较大影响.

3D-QSAR studies of topoisomerase Ⅰ inhibitor homocamptothecin

As a new class of topoisomerase Ⅰinhibitor,homocamptothecin(hCPT) was applied to 3D-QSAR analyses using the comparative molecular field analysis(CoMFA) and comparative molecular similarity index analysis(CoMSIA) methods.Thirty-eight compounds were served to establish the predicting models,The best predictions were obtained with the CoMFA model,q2=0.706,n=6,r2=0.966,S=0.277,F=117.613 and with the CoMSIA model q2=0.696,n=7,r2=0.956,S=0.320,F=74.374.The results suggest that the hydrophobic field and the steric field are very important for activities.With the guidance of the obtained model,some compounds with high activity would be designed.