用比较分子力场和比较分子相似性指数分析方法对氮蒽类化合物抗癌活性的三维定量构效关系研究

用比较分子力场(CoMFA)和比较分子相似性指数分析方法(CoMSIA)对一系列与DNA结合的氮蒽类化合物的潜在抗癌活性进行了3D定量构效关系的研究,对模型中的一些参数进行了优化以期得到最好的三维定量构效关系模型,优化结果显示用CoMSIA构建的模型优于用CoMFA构建的模型.通过CoMSIA分析,用训练集所建立的模型有较好的统计性(20个化合物,q2=0.666,r2=0.916),测试集化合物的预测活性与实验值有很好的一致性.本文还给出了主要分子力场的等势线图.

3D-QSAR study on a series of acridine derivatives as DNA-binding potential antitumor agents using CoMFA and CoMSIA

3D-QSAR and molecular modeling were conducted on a series of DNA-binding potential antitumor agents using comparative molecular field analysis(CoMFA) and comparative molecular similarity indices analysis(CoMSIA). Systematic optimizations of some parameters in the process of model building were performed to search for the best 3D-QSAR model. The calculated results showed that a 3D-QSAR model from CoMSIA was superior to those from CoMFA. Using the best model from CoMSIA analysis, a statistically significant model was obtained from the training set(20 compounds; q2 and r2 values equal to 0.666 and 0.916, respectively), and the predicted antitumor activities of the four compounds in the test set were in good agreement with the measured values. Contour maps of the molecular fields were also presented using the best model.