高等学校化学学报 ›› 2017, Vol. 38 ›› Issue (1): 41-46.doi: 10.7503/cjcu20160643

• 有机化学 • 上一篇    下一篇

类黄酮抑制P糖蛋白的三维定量构效关系与作用模式

刘本国1, 刘江伟1, 李嘉琪2, 耿升1, 莫海珍1, 梁桂兆2()   

  1. 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
  • 收稿日期:2016-09-14 出版日期:2017-01-10 发布日期:2016-12-20
  • 作者简介:联系人简介: 梁桂兆, 男, 博士, 教授, 博士生导师, 主要从事生物医学与健康食品研究. E-mail: gzliang@cqu.edu.cn
  • 基金资助:
    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)和河南省基础与前沿技术研究计划项目(批准号: 162300410177)资助.

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

LIU Benguo1, LIU Jiangwei1, LI Jiaqi2, GENG Sheng1, MO Haizhen1, LIANG Guizhao2,*()   

  1. 1. School of Food Science, Henan Institute of Science and Technology, Xinxiang 453003, China
    2. Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering College,Chongqing University, Chongqing 400044, China
  • Received:2016-09-14 Online:2017-01-10 Published:2016-12-20
  • Contact: LIANG Guizhao E-mail:gzliang@cqu.edu.cn
  • Supported by:
    † Supported by the National Natural Science Foundation of China(Nos.31571782, 21166024), the Program for Innovative Research Team(in Science and Technology) in University of Henan Province, China(No.16IRTSTHN007), the Program for Science & Technology Innovation Talents in Universities of Henan Province, China(No.14HASTIT019) and the Foundation of Research and Advanced Technology of Henan Province, China(No.162300410177).

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rpred2=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.

关键词: 类黄酮, P糖蛋白, 三维定量构效关系, Topomer CoMFA, Surflex-dock

Abstract:

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 multiple correlation coefficients of fitting, cross validation and external validation were 0.971, 0.728 and 0.816, 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.

Key words: Flavonoids, P-glycoprotein, 3D-Quantitative structure-activity relationship, Topomer CoMFA, Surflex-dock

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