【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.更多还原

【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.更多还原