5-脂氧化酶抑制剂酮洛芬酰胺的QSAR研究

摘要

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 cultere 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.%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:PIC50=13.234+0.002Hf+0.010TE+0.948 EHOMO, r2=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.