双酚A类似物雌激素干扰效应的定量结构-活性关系模型  

Predicting Estrogenic Activity of Bisphenols Using Quantitative Structure-Activity Relationships

作　　者：杨先海[1] 刘会会[2] 杨倩[1,3] 刘济宁[1] Yang Xianhai Liu Huihui Yang Qian Liu Jining(Nanjing Institute of Environmental Science, Ministry of Environmental Protection, Nanjing 210042, China Jiangsu Key Laboratory of Chemical Pollution Control and Resources Reuse, School of Environmental and Biological Engineering, Nanjing University of Science and Technology, Nanjing 210094, China The College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing 210009, China)

机构地区：[1]环境保护部南京环境科学研究所,南京210042 [2]南京理工大学环境与生物工程学院江苏省化工污染控制与资源化高校重点实验室,南京210094 [3]南京工业大学生物与制药工程学院,南京210009

出　　处：《生态毒理学报》2016年第4期69-78,共10页Asian Journal of Ecotoxicology

基　　金：国家自然科学基金(No.201507038);江苏省自然科学基金(No.BK20151100);中央级公益性科研院所基本科研业务专项(2015)

摘　　要：由于双酚A(BPA)具有内分泌干扰等毒性效应,有些国家已经开始限制其在部分工业品生产中使用。一些双酚A类似物因用于替代BPA而被大量使用。因其与双酚A具有相似的分子结构,双酚A类似物是否也具有内分泌干扰等毒性效应受到越来越多的关注。采用逐步多元线性回归(MLR)方法,构建了可预测双酚A类似物雌激素效应的定量结构-活性关系模型。模型的决定系数R^2=0.899,去一法交叉验证系数Q_(LOO)~2=0.868,Bootstrapping验证系数Q_(BOOT)~2=0.755,均方根误差RMSE=0.339,表明模型具有较好的拟合优度、稳健性;验证集决定系数Q_(EXT)~2=0.921,外部验证系数Q_(EXT)~2=0.810,均方根误差RMSE=0.638,表明模型具有较好的预测能力。采用欧几里德距离方法和Wil iams图表征了模型应用域,依据分子描述符对模型进行了机理解释,并用所建模型,填补了22种其他双酚A类似物缺失的雌激素干扰效应数据。Due to the endocrine disrupting effects on organisms, bisphenol A （BPA） has been banned from certain products in some countries. Alternatively, BPA analogs （bisphenols） were introduced to replace BPA. However, owing to the structural similarity of those compounds to BPA, there is an increasing concern on the issue that whether bisphenols also could disturb the endocrine system of organisms. In the present study, stepwise multiple linear regressions （MLR） analysis was employed to select variables and develop quantitative structure-activity relationship （QSAR） models for predicting the estrogenic activity of bisphenols. The coefficient determination （R2）, cross validated Q^2 leave-one-out （Q^2LOO）, bootstrapping coefficient （Q^2BOOT） and the root mean square error （RMSE） of the model is 0.899, 0.868, 0.755 and 0.339, respectively, indicating that the model has high goodness-of-fit and robustness. In addition, the coefficient determination （R2EXT）, external validation coefficient （Q^2EXT ） and RMSE of the validation set is 0.921, 0.810 and 0.638, respectively, implying that the model has good predictive ability. The model application domain was characterized by the Euclidean distance and Williams plot. Mechanisms interpretation of the developed model was also performed based on the selected molecular descriptors. Finally, with the help of this model, the data gap for other twenty-two bisphenols on their estrogenic activity was filled.

关 键 词：双酚A类似物 内分泌干扰物 雌激素效应 内分泌干扰效应 定量结构-活性关系 

分 类 号：X171.5[环境科学与工程—环境科学]