通过计算机模拟和体外实验相结合的方法鉴定食品添加剂中的外源性雌激素。
Identification of xenoestrogens in food additives by an integrated in silico and in vitro approach.
作者信息
Amadasi Alessio, Mozzarelli Andrea, Meda Clara, Maggi Adriana, Cozzini Pietro
机构信息
Department of Biochemistry and Molecular Biology, University of Parma, 43100 Parma, Italy.
出版信息
Chem Res Toxicol. 2009 Jan;22(1):52-63. doi: 10.1021/tx800048m.
In the search for xenoestrogens within food additives, we have analyzed the Joint FAO-WHO expert committee database, containing 1500 compounds, using an integrated in silico and in vitro approach. This analysis identified 31 potential estrogen receptor alpha ligands that were reduced to 13 upon applying a stringent filter based on ligand volume and binding mode. Among the 13 potential xenoestrogens, four were already known to exhibit an estrogenic activity, and the other nine were assayed in vitro, determining the binding affinity to the receptor and biological effects. Propyl gallate was found to act as an antagonist, and 4-hexylresorcinol was found to act as a potent transactivator; both ligands were active at nanomolar concentrations, as predicted by the in silico analysis. Some caution should be issued for the use of propyl gallate and 4-hexylresorcinol as food additives.
在对食品添加剂中的外源性雌激素进行研究时，我们使用计算机模拟和体外实验相结合的方法，分析了联合国粮食及农业组织-世界卫生组织联合专家委员会数据库，该数据库包含1500种化合物。通过分析，我们确定了31种潜在的雌激素受体α配体，在根据配体体积和结合模式应用严格筛选标准后，这一数量减少至13种。在这13种潜在的外源性雌激素中，有4种已被证实具有雌激素活性，另外9种进行了体外实验，测定了它们与受体的结合亲和力及生物学效应。结果发现，没食子酸丙酯具有拮抗作用，4-己基间苯二酚具有强效反式激活作用；正如计算机模拟分析所预测的那样两种配体在纳摩尔浓度下均具有活性。对于将没食子酸丙酯和4-己基间苯二酚用作食品添加剂，应予以一定的谨慎对待。
Zotero 插件