利用SAS9.0对卤代苯酚类化合物小鼠口服LD_(50)定量构效关系的研究  

Study on the Quantitative Structure-Toxicity Relationships of Halogenated Phenols in Mouse via Oral LD_(50) Using SAS9.0

作　　者：闫心丽[1] 李佐静[1] 孙也之[2] 孟繁浩[2] 

机构地区：[1]沈阳药科大学基础学院,辽宁沈阳110016 [2]中国医科大学药学院,辽宁沈阳110001

出　　处：《辽宁大学学报（自然科学版）》2007年第4期361-365,共5页Journal of Liaoning University：Natural Sciences Edition

基　　金：国家自然科学基金资助项目(30571591)

摘　　要：利用SAS 9.0中的最小R2增量法选择法,对卤代苯酚类化合物小鼠口服LD50的定量构效关系进行了研究.利用计算机应用程序,在AM1和PM3模式下计算了30个卤代苯酚类化合物的14种量化参数,用24个化合物研究它们对小鼠口服急性毒性(LD50)的影响,经统计分析,又引入了多个参数的交叉项,以消除参数间的共线性.利用线性回归方法获得苯酚类化合物小鼠经口急性毒性预测模型.经模型验证及leave-one-out交互验证,筛选出下面的模型:Logtox=0.00003464*TTT+0.56640*Polar+0.00091484*LHP-0.00214*PH-0.00001903*LEC,(R-Square=0.9917 and C(p)=5.0000).用另6个化合物作为测试集,证明该模型具有很好的预测能力,取得了良好的结果,为定量评估和预测其他卤代苯酚类化合物的有机毒性提供了良好的QSAR模型.The Quantitative Structure-Toxicity Relationships （QSTR） of halogenated phenols in mouse via oral LD50 was studied using MINR method of SAS 9.0. 14 kinds of quantum chemistry parameters of 30 kinds of halogenated phenols were calculated under AM1 and PM3 mode using computer program. The effect of quantum chemistry parameters on the acute toxicity of 24 halogenated phenols was studied, 10 kinds of predicting models obtained using linear regression model method as well. After model test and leave-one-out test the following model was obtained ： Logtox=0. 14490 ＊ Tenergy ＋ 0. 03987 ＊ Volume ＋ 0. 01454 ＊ AreaApp - 0.81760 ＊ Polar - 0. 00115 ＊ LC （ R - Square = 0.9741 and C （p） = 5. 0000）. Six halogenated phenols were used to test the toxicity prediction, which showes that the model has a good forecasting ability and it could be used in the studying toxicity and the predicting toxicity of halogenated phenols.

关 键 词：卤代苯酚类化合物 构效关系 SAS 9.0 毒性预测 

分 类 号：R927.2[医药卫生—药学]