有机污染物的混合毒性QSAR模型及其机制研究进展

发布时间：2019-06-18 23:50

【摘要】：环境有机污染物的联合暴露是一条普遍规律.化合物定量结构与活性相关研究(quantitative structure-activity relationship,QSAR)模型是研究有机污染物毒性的重要方法.本文以有机污染物的混合毒性及其机制研究为主线,将化合物按照毒性作用方式分为3类:非极性麻醉型、极性麻醉型和反应性化合物,并概述了3类化合物基于毒性作用机制的混合毒性QSAR模型.简单综述了非极性麻醉型化合物混合毒性的定量预测方法,发现非极性麻醉型化合物的毒性预测方法最为简单,仅由混合体系的总疏水性决定,可通过统一的QSAR模型预测;概述了极性麻醉型化合物混合毒性的定量预测方法,指出极性麻醉型化合物的混合毒性由混合体系总疏水性和氢键效应共同决定;重点解析了反应性化合物的混合毒性QSAR模型,发现由于反应性化合物作用机制较为复杂,目前仍缺乏统一的混合毒性定量预测方法.进一步从混合物组分、化合物之间相互作用和化合物与靶蛋白的相互作用3方面入手,综述了反应性化合物混合毒性QSAR模型的最新研究进展.最后指出,采用基因组学和代谢组学等更为先进的实验手段进一步揭示化合物的分子生物学机制,进而建立更为通用的有机污染物混合毒性预测方法是今后发展的方向.
[Abstract]:The combined exposure of environmental organic pollutants is a general law. Quantitative structure and activity related study (quantitative structure-activity relationship,QSAR) model is an important method to study the toxicity of organic pollutants. In this paper, based on the study of mixed toxicity and its mechanism of organic pollutants, compounds are divided into three categories according to the mode of toxicity: non-polar anesthetic type, polar anesthetic type and reactive compound, and the mixed toxic QSAR model of three kinds of compounds based on toxic mechanism is summarized. In this paper, the quantitative prediction methods of mixed toxicity of non-polar anesthetic compounds are briefly reviewed, and it is found that the toxicity prediction method of non-polar anesthetic compounds is the simplest, which can only be determined by the total hydrophobicity of the mixed system and can be predicted by the unified QSAR model, and the quantitative prediction method of the mixed toxicity of polar anesthetic compounds is summarized, and it is pointed out that the mixed toxicity of polar anesthetic compounds is determined by the total hydrophobicity and hydrogen bond effect of the mixed system. The mixed toxicity QSAR model of reactive compounds is analyzed. It is found that there is still a lack of a unified quantitative prediction method for mixed toxicity because of the complexity of the mechanism of action of reactive compounds. Furthermore, the latest research progress of QSAR model of mixed toxicity of reactive compounds was reviewed from three aspects: mixture composition, interaction between compounds and target proteins. Finally, it is pointed out that it is the development direction in the future to further reveal the molecular biological mechanism of compounds by using more advanced experimental methods such as genomics and metabonomics, and then to establish a more general method for predicting the mixed toxicity of organic pollutants.
【作者单位】：同济大学污染控制与资源化研究国家重点实验室;区域环境质量协同创新中心;安阳工学院化学与环境工程学院;同济大学上海市化学品分析、风险评估与控制重点实验室;
【基金】：国家自然科学基金(201177092,21377096,U1404217) 同济大学污染控制与资源化研究国家重点实验室自主研究(重点)项目(PCRRY11003) 同济大学英才(攀登)计划(0400219287) 上海市科学技术委员会(14DZ2261100)资助
【分类号】：X171.5

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