环己烯类神经氨酸酶抑制剂的三维定量构效关系研究

Three Dimensional Quantitative Structure-activity Relationship of Cyclohexene Neuraminidase Inhibitors

环己烯类神经氨酸酶抑制剂是目前效果最好的流感病毒抑制剂.选取26个典型的环己烯类神经氨酸酶抑制剂,应用比较分子力场分析(CoMFA)方法,研究它们与神经氨酸酶(NA)的相互作用,建立了环己烯类NA抑制剂与NA的三维定量构效关系(3D-QSAR)模型.该模型的最佳非交叉验证系数R2为0.991,交叉验证系数R2cv为0.760,检测值F为521.53,标准偏差SEE为0.098,立体场、静电场的贡献分别为74.6%、25.4%,最佳主成分为4,这表明模型具有很强的稳定性和预测能力.用该模型对随机挑选的3个化合物进行预测,得到了满意的结果.

Cyclohexene neuraminidase inhibitors are the best inhibitors of influenza virus.The interaction of between neuraminidase and 26 cyclohexene neuraminidase inhibitors were studied by comparative molecule field analysis（CoMFA）.The 3D-QSAR model was constructed with the cross validated correlation of R2cv=0.760,non-cross-validation correlation coefficient of R2=0.991,F value of 521.53 and standard deviation of 0.098.The results shown that the optimum main component is 4 and the contribution of steric field and electrostatic fields reached 74.6% and 25.4% in the proposed model.The model was successfully applied in the prediction of 3 compounds with satisfactory results.