Waller C L, Minor D L, McKinney J D
Environmental Toxicology Division, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA.
Environ Health Perspect. 1995 Jul-Aug;103(7-8):702-7. doi: 10.1289/ehp.95103702.
Certain phenyl-substituted hydrocarbons of environmental concern have the potential to disrupt the endocrine system of animals, apparently in association with their estrogenic properties. Competition with natural estrogens for the estrogen receptor is a possible mechanism by which such effects could occur. We used comparative molecular field analysis (CoMFA), a three-dimensional quantitative structure-activity relationship (QSAR) paradigm, to examine the underlying structural properties of ortho-chlorinated hydroxybiphenyl analogs known to bind to the estrogen receptor. The cross-validated and conventional statistical results indicate a high degree of internal predictability for the molecules included in the training data set. In addition to the phenolic (A) ring system, conformational restriction of the overall structure appears to play an important role in estrogen receptor binding affinity. Hydrophobic character as assessed using hydropathic interaction fields also contributes in a positive way to binding affinity. The CoMFA-derived QSARs may be useful in examining the estrogenic activity of a wider range of phenyl-substituted hydrocarbons of environmental concern.
某些受环境关注的苯基取代烃有可能扰乱动物的内分泌系统，这显然与其雌激素特性有关。与天然雌激素竞争雌激素受体是可能产生此类效应的一种机制。我们使用比较分子场分析（CoMFA），一种三维定量构效关系（QSAR）范式，来研究已知与雌激素受体结合的邻氯羟基联苯类似物的潜在结构特性。交叉验证和传统统计结果表明训练数据集中包含的分子具有高度的内部可预测性。除了酚（A）环系统外，整体结构的构象限制似乎在雌激素受体结合亲和力中起重要作用。使用疏水相互作用场评估的疏水特性也对结合亲和力有积极贡献。源自CoMFA的QSAR可能有助于研究更广泛的受环境关注的苯基取代烃的雌激素活性。
