梨形四膜虫细胞毒性苯酚类似物的三维定量结构毒性相关研究

摘要

目的 使用比较分子相似性指数分析(CoMSIA)方法 对梨形四膜虫细胞毒性苯酚类似物进行三维定量结构毒性相关(3D-QSTR)研究.方法 系统分析了立体场、静电场、疏水场对三维结构毒性模型的影响,并建立相应的3D-QSTR预测模型.结果 使用静电场与疏水场协同作用建立了具有良好可靠性和预测能力的3D-QSTR模型(Q2=0.767,r2=0.933).结论 模型具有良好的预测能力,对苯酚类似物的结构修饰具有指导作用.%Objective To use the comparative molecular similarity indices analysis (CoMSIA) for constructing three dimension quantitative structure-toxicity relationship (3D-QSTR) models of phenolic analogues with cytotoxicity against Tetrahymena pyri-formis. Methods The contribution of hydrophobic,electrostatic and steric property to 3D-QSTR models were analyzed comprehensively. The optimized 3D-QSTR model was constructed by CoMSIA using electrostatic and hydrophobic properties for phenolic ana-loguesResults The model had good stability (Q2 =0. 767) and predictive ability (r2 =0. 933). Conclusion The electrostatic and hydrophobic counter maps from CoMSIA could guide the structural modification of phenolic analogues directly.