化合物毒性及三维结构参数的定量构效关系研究  

3D-QSAR Discovery of Toxicity and Chemical Parameters of Benzene Drugs

作　　者：郭亦然[1] 张燕玲[1] 艾路[1] 乔延江[1] 

机构地区：[1]北京中医药大学中药学院,北京100102

出　　处：《现代生物医学进展》2006年第4期22-24,共3页Progress in Modern Biomedicine

基　　金：国家自然科学基金(No.30472180);国家中医药管理局科学研究专向课题基金(04-05zp03)资助项目

摘　　要：目的:建立小分子化合物毒性的三维定量构效关系模型,探索化合物毒性数据和三维结构参数之间关系的方法。方法:利用比较分子力场分析方法(CoMFA),建立了一组对发光菌有急性毒性的小分子的三维定量构效模型。结果:模型的交叉验证相关系数q2=0.731,非交叉验证相关系数r2=0.973,标准偏差SE=0.122,F=70.910。结论:该模型具有较好的预测能力,表明在甲基的邻对位减小取代基体积或电负性可以降低化合物毒性。Objective： To predict the relationship between the toxicity and the structural parameters of Benzene drugs, a 3D - QSAR （three dimensional quantitative structure - activity relationship） model was established. Methods ： By determining their lowest energy conformation, molecules are aligned aceording 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 and steric interaction energies 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 Field Analysis （CoMFA） model was built. Results： The crossvalidated q^2 of the model is 0.731 and the cross- validated r^2 is 0.973, so the predictive abilities of these models are considerable. Conclusion： This model has a good predictive ability. To reduce the bulk of substitutent in the paraposition and ortho - position of methyl or decrease the negative charge of substitutent in the para - position and ortho - position of methyl can increase the toxicity.

关 键 词：化合物毒性 三维构效关系 比较力场分析方法 

分 类 号：O621.15[理学—有机化学] TQ450.11[理学—化学]