QSAR trout toxicity models on aromatic pesticides

The pesticides originally designed to kill target organisms are dangerous for many other wild species. Since they are applied directly to the environment, they can easily reach the water basins and the topsoil. A dataset of 125 aromatic pesticides with well-expressed aquatic toxicity towards trout was subjected to quantitative structure activity relationships (QSAR) analysis aimed to establish the relationship between their molecular structure and biological activity. A literature data for LC₅₀ concentration killing 50% of fish was used. In addition to the standard 2D-QSAR analysis, a comparative molecular field analysis (CoMFA) analysis considering the electrostatic and steric properties of the molecules was also performed. The CoMFA analysis helped the recognition of the steric interactions as playing an important role for aquatic toxicity. In addition, the transport properties and the stability of the compounds studied were also identified as important for their biological activity.     

精确三维光谱数据活性关系方法应用于ToxCast数据库中雌激素受体数据分类、验证和特征提取的建模策略

本文利用三维光谱数据活性关系方法(3D-SDAR)对ToxCast数据库中1 528种化合物的雌激素潜能(表示为18分复合高通量筛选生物测定)进行建模。由于缺少170核磁共振(NMR)仿真软件，信息量最大的碳-碳3D-SDAR指纹随着一些指标变量增强，这些指标变量包括来自羰基和酰胺的氧原子、酯基、磺酰、硝基、脂肪族羟基和酚羟基官能团。为了评价本文作者所开发模型的预测性能的真实性，美国环境保护署为研究人员提供了2 008种化合物组成一套盲测。其中，543种化合物有文献可查数据—他们的结合力有助于评估开发模型的外部分类精度：得到预测精度0.62，敏感度0.71，和特异度0.53的结果。与其他建模技术相比，本文作者开发的模型几乎没有简化建模集和预测集之间的性能。3D-SDAR映射技术可以识别拟雌激素活性所必需的结构特征：1) 存在一个酚的OH官能团或环己烯酮，2)与第一苯酚环上的氧距离6 ?到8 ?的第二芳香或酚环，3) 存在一个与苯酚环的几何中心距离大约6 ?的甲基官能团，4)一个靠近(距离几何中心～4?)某个苯酚环的羰基官能团。
精选自Svetoslav H. Slavov, Richard D. Beger. Rigorous 3-dimensional spectral data activity relationship approach modeling strategy for toxcast estrogen receptor data classification, validation, and feature extraction. Environmental Toxicology and Chemistry: Volume 36, Issue 3, pages 823–830, July 2017. DOI: 10.1002/etc.3578
详情请见http://onlinelibrary.wiley.com/wol1/doi/10.1002/etc.3578/full
     

QSAR trout toxicity models on aromatic pesticides

The pesticides originally designed to kill target organisms are dangerous for many other wild species. Since they are applied directly to the environment, they can easily reach the water basins and the topsoil. A dataset of 125 aromatic pesticides with well-expressed aquatic toxicity towards trout was subjected to quantitative structure activity relationships (QSAR) analysis aimed to establish the relationship between their molecular structure and biological activity. A literature data for LC50 concentration killing 50% of fish was used. In addition to the standard 2D-QSAR analysis, a comparative molecular field analysis (CoMFA) analysis considering the electrostatic and steric properties of the molecules was also performed. The CoMFA analysis helped the recognition of the steric interactions as playing an important role for aquatic toxicity. In addition, the transport properties and the stability of the compounds studied were also identified as important for their biological activity.