5-脂氧化酶抑制剂酮洛芬酰胺的QSAR研究

QSAR Study of Ketoprofen Amides as 5-lipoxygenase inhibitors

用半经验量子软件MOPAC2012,PM7水平上,对20种酮洛芬酰胺化合物分子进行几何优化,计算EHOMO、ELUMO、Hf、MR等量子化学参数,将计算得到的量子化学参数与酮洛芬酰胺对5-脂氧化酶(5-LOX)抑制活性进行关联,并通过有进有出的逐步回归分析,筛选了影响抑制5-LOX的主要因素,建立了定量构效关系模型,最优模型为:PIC_(50)=13.234+0.002Hf+0.010TE+0.948 EHOMO,r^2=0.806,F=22.174,N=20,r2CV=0.671,s=0.139。利用VIF检验各参数相关性,用LOO法对所建模型进行显著性及预测能力的检验。计算结果显示,影响化合物抑制5-LOX的主要因素是化合物的生成热、总能量、最高占有轨道能级。该研究可为研制COX-2和5-LOX双重抑制酮洛芬衍生物提供理论指导。

A series of ketoprofen amides against 5 -LOX were subjected to structure- activity relationship（QSAR） analysis. The result of the study shows that the inhibit activity, as determined in the cell cuhere model, was highly correlated with the electronic （HOMO） and the thermodynamic （ heat of formation and Total energy）. The relationship can be expressed by the following regression equation ： PIC50 = 13. 234 ＋0.002Hf ＋0.010TE ＋0.948EHOMO, r2 =0.806 ,F =22. 174 ,N =20, r2CV = 0.671, s = 0. 139. The results may contribute to better designing novel ketoprofen derivatives , COX -2 and 5 - LOX inhibitors.