(E)-4-取代酰氧基-3-甲氧基苯乙烯侧链类衍生物的比较分子力场(CoMFA)研究

Comparative molecular field analysis(CoMFA) study on (E)-4-subsituted cinnamoyloxy-3-methoxystyrene side line derivatives

利用比较分子力场方法,建立5-脂氧合酶/环氧合酶抑制剂的三维定量构效关系,为设计新的更有效的酶抑制剂提供理论依据.在CoMFA分析中,交叉验证回归系数R2CV、非交叉验证回归系数r2和标准偏差(SEE)分别为0.639,0.744,0.148.说明系列化合物分子周围立体场和静电场的分布与抗炎活性间有良好的相关性.利用该模型对自行合成的24个化合物进行活性预测,结果与实测值相符.所得模型支持了假设的抑制剂作用机理和作用模型.所得CoMFA模型具有一定的预测能力,可用来指导设计新的5-脂氧合酶/环氧合酶抑制剂.

Comparative molecular field analysis （CoMFA） was performed to study 3D-QSAR of （E）-4-cinnamoyloxy-3-methoxystyrene derivatives with biological activity in order to give a theoretical basis to design novel more effective enzyme dual inhibitor. In this analysis, the cross validated coefficient R^2cv was found to be 0.639, non-cross validated coefficient r^2 and the standard deviation SEE was 0.744 and 0. 148 respectively, and F was 198. 355. The CoMFA models for twenty four of （E）-4-cinnamoyloxy-3-methoxystyrene derivatives showed the good relationship between steric and electrostatic properties with anti-inflammatory activity, which were very helpful for designing novel compounds as 5-lipoxygenase/cyclooxygenase inhibitor.