羟基多溴二苯醚生物活性的QSAR研究  

QSAR Study on Bioactivity of Hydroxylated Polybrominated Diphenyl Ethers

作　　者：易忠胜[1] 李连臣[1] 叶廷文[1] 刘红艳[1] 莫凌云[1,2] 

机构地区：[1]桂林理工大学化学与生物工程学院,广西桂林541004 [2]广西师范大学珍稀濒危动植物生态与环境保护省部共建教育部重点实验室,广西桂林541004

出　　处：《桂林理工大学学报》2011年第3期430-438,共9页Journal of Guilin University of Technology

基　　金：广西自然科学基金项目(2011GXNSFA018061);广西教育厅科研项目(200708LX265);珍稀濒危动植物生态与环境保护省部共建教育部重点实验室研究基金(桂科能1002K001)

摘　　要：采用VSMP方法从大量的分子结构描述符中筛选最优子集,用多元线性回归方法分别构建了羟基多溴二苯醚(hydroxylated polybrominated diphenyl ethers,OH-PBDEs)对细胞色素CYP19介导类固醇生成的抑制活性,甲状腺受体-β(thyroid receptors,TR-β)的激素活性以及与甲状腺素结合球蛋白(thyrox-ine-binding globulin,TBG)和甲状腺转运蛋白(transthyretin,TTR)之间结合能力的定量构效关系(quantita-tive structure-activity relationship,QSAR)模型。模型的留一法交叉验证(leave-one-out cross validation,LOO-CV)相关系数Q2和拟合相关系数R2均高于0.95和0.97,表明模型具有良好的稳健性、拟合能力和预测能力。QSAR模型表明OH-PBDEs的分子三维结构和芳香性是其活性的重要影响因素。另外,分子中溴原子数量和取代位置对OH-PBDE生物活性具有重要影响。Quantitative structure-activity relationship（QSAR）models are developed to predict the bioactivities of hydroxylated polybrominated diphenyl ethers（OH-PBDEs）.The bioactivities are inhibition of steroidogenesis mediated by CYP19,hormone activity to thyroid receptor-β（TR-β）,and binding interaction with thyroxine-binding globulin（TBG） and transthyretin（TTR）.The VSMP（variable selection and modeling based on the prediction） technique is used to select optimal subset from large-size molecular descriptors.Multiple linear regression（MLR） method is employed to construct the QSAR models.The correlation coefficient of leave-one-out cross validation（Q2） and fitting correlation coefficient of models（R2） of four QSAR models are greater than 0.95 and 0.97 respectively.The statistics parameters show that overall models are robust and have good fitting and prediction for selecting bioactivities.The standard regression coefficients of models reveal that the 3D structure and aromaticity of OH-PBDEs are the most important factors for the bioactivities.In addition,the number and the position of bromine play an important role in the bioactivities of OH-PBDEs.

关 键 词：羟基多溴二苯醚(OH-PBDEs) 细胞色素CYP19 甲状腺受体-β(TR-β) 甲状腺素结合球蛋白(TBG) 甲状腺转运蛋白(TTR) 

分 类 号：X132[环境科学与工程—环境科学]