分子电性距离矢量用于三嗪类化合物的构效关系研究

Application of Molecular Electronegativity Distance Vector to the Quantitative Structure-Activity Relationship Study on Triazines

采用分子电性距离矢量(Molecular Electronegativity Distance Vector,MEDV)表征了三嗪类化合物的分子结构,并运用多元线性回归(Multiple Linear Regression,MLR)建立了该类化合物结构与其发光菌和大型蚤毒性的定量结构-毒性相关(Quanti-tative Structure-Toxicity Relationship,QSTR)模型,同时采用留一法交互检验对所建模型进行了分析和验证,建模计算值的相关系数R分别为0.970和0.952,留一法交互检验预测值的相关系数RLOO分别为0.917和0.921,并进一步阐述了结构与毒性之间的关系。结果表明,三嗪环上π电子离域程度减小有利于毒性增加,侧链N上取代基数目增加,化合物毒性减小。为进一步预测该类化合物的毒性,进行药物筛选提供了有效的理论依据。

The molecular electronegativity distance vector（MEDV）was used to describe the chemical structure of triazines. With the help of multiple linear regression （MLR）, the quantitative structuretoxicity relationship（QSTR）model was established. The estimation stability and generalization ability of the model were strictly analyzed by the leave-one-out （LOO） cross validation（CV） technique. The R values were 0. 970 and 0. 952 ,RLOO values were 0. 917 and 0. 921, respectively, for the calculated results and those predicted by LOO-CV. The relationship between structure and toxicity has been discussed. The result shows that：following the reduction of the extent of re electronic delocalization of triazine ring, the toxicity will increase. The triazine＇s toxicity would be reduced by increasing the number of substitute groups on the side chain nitrogen. The proposed method provides an important support and is useful for prediction the toxicity of triazines and drug screening.