Interactions of bisphenol diglycidyl ethers with estrogen receptors α: fluorescence polarization, reporter gene, and molecular modeling investigations

Abstract Based on human estrogen receptor α ligand binding domain (hERα-LBD) as recognition element, a fluorescence polarization assay was developed for the determination of bisphenol A diglycidyl ether (BADGE), bisphenol F diglycidyl ether (BFDGE), and their derivatives. Fluorescence polarization assay showed that BADGE, BFDGE and their derivatives exhibited dose-dependent binding to the receptor protein. The results of reporter gene assay indicated that all the tested bisphenol diglycidyl ethers show no agonistic activities, but some of them exhibit anti-estrogenic activities toward ERα. All the tested bisphenol diglycidyl ethers fitted into the hydrophobic binding pocket and adopted the conformation that resembled 4-hydroxytamoxifen, a selective antagonist of ERα. Quantitative structure-activity relationship analysis showed that the binding potencies of bisphenol diglycidyl ethers with hERα-LBD might be structure-dependent. This work may provide insight into the in silico screening of ER ligands from unsuspected chemicals.