氯代芳烃类化合物毒性及三维结构的定量关系研究

3D-QSAR Discovery of Toxicity and Chemical Parameters of chloro-Arenes Drugs

摘要:

目的:建立氯代芳烃类化合物毒性的三维定量构效关系模型,探索研究化合物毒性数据和三维结构参数之间关系的新方法。方法:利用比较分子相似性指数分析方法(CoMSIA),建立了一组具有发光菌毒性的氯代芳烃类共化合物的三维定量构效关系模型。结果:得到了较好的构效关系模型,其交叉验证相关系数q²=0.702,非交叉验证相关系数r²=0.947,标准偏差SE=0.151,F=18.027。结论:该模型具有较好的预测能力,表明降低甲基对位负电性或减弱甲基邻位、间位、对位取代基亲水性可以降低化合物毒性。

Abstract:

Objective: To predict the relationship between the toxicity and the structural parameters of chloro-Arenes drugs,a 3D-QSAR(three dimensional quantitative structure-activity relationship) model was established.Methods: By determining their lowest energy conformation,molecules are aligned according to one specific rule and the scope of the molecular field is defined around the aligned molecules.The characters of the molecule field such as the electrostatic field energy,steric field energy and also the field energy of hydrophobic region are calculated.Then Partial Least Square(PLS) method is exploited to analyze the relationship between the toxicity of compounds and characters of the molecular field and finally Comparative Molecular Similarity Indices Analysis(CoMSIA) model was built.Results:The cross-validated q² of the model is 0.702 and the cross-validated r² is 0.947,so the predictive abilities of this model is considerable.Conclusion:This model has a good predictive ability.To decrease the negative charge of substitutent in the para-position of methyl or decrease the hydrophilic property of substitutent in the para-position,meta-position and ortho-position of methyl can decrease the toxicity.