抗癌性AHMA衍生物三维定量构效关系研究

3D-QSAR Study of AHMA Derivatives as Potent Anticancer Agents

应用比较分子场分析法(CoMFA)对一系列抗癌性AHMA类衍生物进行了三维定量构效关系(3D-QSAR)研究,建立了交叉验证的CoMFA模型。所建最佳模型的交叉验证相关系数q2为0.702,非交叉验证相关系数r2为0.993,估算的标准误差S=0.085,统计方差比F(4,25)=448.5,用该模型对测试集化合物进行了预测,预测结果与实验值非常接近,表明模型具有很好的预测能力。论文对该系列抗癌化合物的三维定量构效关系进行了深入讨论,结果进一步表明,在R取代基第一个原子上引入拉电子基团或原子,同时选择给电子的R1基团及较大体积的取代基R2,能有效地改善这类化合物的抗癌活性。

Comparative molecular field analysis （CoMFA） method was applied to the study of the three-dimensional quantitative structure activity relationship （3D-QSAR） on a series of AHMA derivatives as potent anticancer agents. The CoMFA model of cross- validation has been well built. The best CoMFA model gives a good cross - vali- dated value （q^2） of 0. 702 with an optimized component of 4, and a conventional correlation coefficient （ r^2 ） of 0. 993. Moreover, the estimated standard error （S） is 0. 085 and the statistical square deviation radio （F） is 448.5. The statistic parameters of the best CoMFA model show the model is reasonable and predictive. Seven compounds in test set were predicted and the result is closed to that of experiment. The analysis of CoMFA model suggests that selecting the R with an electron-withdrawing atom or group linking to its first atom, the R1 with electron- donating and the R2 with big volume will improve the activity.