类黄酮抑制P糖蛋白的三维定量构效关系与作用模式  

3D-QSAR and Interaction Mechanism of Flavonoids as P-glycoprotein Inhibitors

作　　者：刘本国[1] 刘江伟[1] 李嘉琪[2] 耿升[1] 莫海珍[1] 梁桂兆[2] LIU Benguo LIU Jiangwei LI Jiaqi GENG Sheng MO Haizhen LIANG Guizhao(School of Food Science, Henan Institute of Science and Technology, Xinxiang 453003, China Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400044, China)

机构地区：[1]河南科技学院食品学院,新乡453003 [2]重庆大学生物工程学院,生物流变科学与技术教育部重点实验室,重庆400044

出　　处：《高等学校化学学报》2017年第1期41-46,共6页Chemical Journal of Chinese Universities

基　　金：国家自然科学基金(批准号:31571782,21166024);河南省高校科技创新团队(批准号:16IRTSTHN007);河南省高校科技创新人才项目(批准号:14HASTIT019);河南省基础与前沿技术研究计划项目(批准号:162300410177)资助~~

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r^2=0.971,q^2=0.728和r^2_(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.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.

关 键 词：类黄酮 P糖蛋白 三维定量构效关系 Topomer COMFA Surflex-dock 

分 类 号：O621[理学—有机化学] R914[理学—化学]