王悦,吕钧慧,周蕾,肖寒,范晓琳,贾晓静,陶虎,张照斌.对烷氧基苯酚类物质(p-AOPs)的雌激素活性[J].环境科学学报,2019,39(4):1324-1331
对烷氧基苯酚类物质(p-AOPs)的雌激素活性
- Study on the estrogenic activity of p-alkoxyphenols
- 基金项目：国家重点研发计划（No.2017YFF0211202）；政府间国际科技创新合作重点专项（No.2016YFE0117800）；国家自然科学基金（No.21777003，41330637，21377007）
- 王悦
- 1. 西北农林科技大学理学院, 杨凌 712100;2. 北京大学城市与环境学院, 北京 100871
- 吕钧慧
- 1. 西北农林科技大学理学院, 杨凌 712100;2. 北京大学城市与环境学院, 北京 100871
- 范晓琳
- 北京大学城市与环境学院, 北京 100871
- 贾晓静
- 北京大学城市与环境学院, 北京 100871
- 张照斌
- 北京大学城市与环境学院, 北京 100871
- 摘要：对烷氧基苯酚（p-AOPs）是一类广泛应用于化工业、制药业、化妆品等领域的苯酚类化合物，其结构与具有雌激素活性的烷基酚类物质相似，但目前对于p-AOPs的雌激素活性尚未见文献报道.本文利用分子对接技术，预测了常见p-AOPs在人雌激素受体α（hERα）激动剂口袋中的结合情况，发现p-AOPs能够很好地与hERα结合，其酚羟基能够与hERα的Glu353和Arg349形成氢键，疏水区域可以与Phe404等疏水氨基酸产生疏水相互作用；通过磷酸对硝基苯酚法对8种p-AOPs的雌激素活性进行分析，发现4-苯氧基苯酚（PhOP）、4-戊氧基苯酚（PeOP）、4-苄氧基苯酚（PBP）具有较强的雌激素活性，其EC50值分别达到9.41×10-7、1.89×10-6和2.68×10-6 mol·L-1.与典型环境雌激素双酚A（BPA）的雌激素活性相比，PhOP活性明显强于BPA，而PeOP和PBP与BPA接近.通过分析不同烷基碳链长度的p-AOPs的雌激素活性发现，烷基链碳数在1~5个范围内，碳链越长雌激素活性越大.鉴于p-AOPs具有较强雌激素活性，且其广泛应用于与人体密切接触的一些领域，建议进一步加强对这类物质的人体暴露量、内分泌干扰危害和健康风险的研究.
- Abstract：p-Alkoxyphenols (p-AOPs) are a class of phenolic compounds, which are widely used in chemical industry, cosmetics and pharmaceuticals. The structures of p-AOPs are similar to p-alkylphenols, a well-known estrogenic compounds. However, few studies have reported the estrogenic activity of p-AOPs to date. In this study, we predicted the binding affinities of p-AOPs to human estrogen receptor alpha (hERα) by molecular docking and found that p-AOPs could well bind to hERα agonist pocket. Hydrogen bonds formed between the phenolic hydroxyl group of p-AOPs with Glu315 and Arg349 of hERα and hydrophobic interactions of the phenyl ring and alkyl group of p-AOPs with the core hydrophobic moiety provided by the hydrophobic amino acids of hERα pocket are the important feature of the binding. The estrogenic activities of eight p-alkoxyphenols were then analyzed by using hERα coactivator recruiting assay. p-phenoxyphenol (PhOP), p-pentyloxyphenol (PeOP) and p-benzyloxyphenol (PBP) were found to show strong estrogenic activity, of which the EC50 values were close to the typical environmental estrogen, bisphenol A (BPA), reaching 9.41×10-7, 1.89×10-6 and 2.68×10-6 mol·L-1, respectively. The estrogen activities of p-alkoxyphenols with 1~5 alkyl carbon chains showed the pattern that the longer alkyl chain possessed the higher estrogenic activity. In view that the strong estrogenic activities of p-alkoxyphenols and their widespread uses, further research on their endocrine effects and health risk assessment are needed.
