中文摘要：

采用基于R基团搜索技术的Topomer CoMFA建立了30个类黄酮类P糖蛋白抑制剂的三维定量构效关系（3D-QSAR）模型,并用包括9个样本的测试集验证模型的外部预测能力.所得模型的拟合、交互验证以及外部验证的复相关系数分别为r2=0.971,q2=0.728和r2（pred）=0.816.在此基础上,运用Surflex-dock分子对接法研究了白杨素及其异戊烯化衍生物与P糖蛋白的作用模式.结果表明,异戊烯化修饰可显著提高类黄酮的亲脂性,修饰产物能更好地与P糖蛋白的疏水性口袋契合,二者结合程度高.

英文摘要：

A 3D-QSAR model of 30 flavonoids as P-glycoprotein inhibitors was constructed using Topomer CoMFA. Nine flavonoids were used to validate the external predictive power of the obtained model. The multi- ple correlation coefficients of fitting, cross validation and external validation were 0. 971, 0. 728 and O. 816, respectively. The molecular docking modes of chrysin and its prenylated derivatives were established by the Surflex-dock method. The results showed the lipophilicity of flavonoids could be improved by the prenyl modification, which resulted to the stronger interaction with the hydrophobic pocket of P-glycoprotein.