黄酮类醛糖还原酶抑制剂的三维定量构效关系研究

目的：建立黄酮类化合物抑制剂活性的三维定量构效关系模型，为进一步进行黄酮类醛糖还原酶抑制剂（ARI）的活性与三维结构关系的研究提供重要依据。方法：采用比较分子力场分析法（CoMFA）和比较分子相似性指数分析法（CoMSIA），系统研究了75个新型ARI的三维定量构效关系。结果：CoMFA和CoMSIA模型的交互验证相关系数q^2值分别为0.603和0．706、非交互验证相关系数r2值分别为0.956和0.900。结论：CoMFA和CoMSIA模型均具有较强的预测能力，CoMFA和CoMSIA模型的三维等值线图直观地解释了化合物的构效关系，阐明了化合物结构中各位置取代基对黄酮类醛糖还原酶抑制剂活性的影响，为进一步结构优化提供了重要理论依据。

Three-Dimensional Quantitative Structure Activity Relationship of Flavones as Aldose Reductase Inhibitors

Objective: To establish the model of three-dimensional quantitative structure activity relationship (3D-QSAR) of flavones as aldose reductase inhibitors (ART) and provide important data for the study of this model. Methods: 3D-QSAR of 75 flavones, new ARI, was studied by CoMFA (=comparative molecular field analysis) and CoMSIA (=comparative molecular similarity indices analysis) methods. Results: The LOO (Leave-one-out) cross validation correlation coefficients (q2) were 0.603 and 0.706 for CoMFA and CoMSIA models, respectively. The calibrated correlation coefficients (r2) were 0.956 and 0.900, respectively. There was statistically significant difference between the two methods. Conclusion: Both CoMFA and CoMSIA have strong prediction function, whose contour maps have shown the conformation of the compounds, which can offer theoretical basis for further conformation optimization.