title: Estrogenic activity data extraction and in silico prediction show the endocrine disruption potential of bisphenol A replacement compounds.
abstract: Bisphenol A (BPA) replacement compounds are released to the environment and cause widespread human exposure. However, a lack of thorough safety evaluations on the BPA replacement compounds has raised public concerns. We assessed the endocrine disruption potential of BPA replacement compounds in the market to assist their safety evaluations. A literature search was conducted to ascertain the BPA replacement compounds in use. Available experimental estrogenic activity data of these compounds were extracted from the Estrogenic Activity Database (EADB) to assess their estrogenic potential. An in silico model was developed to predict the estrogenic activity of compounds lacking experimental data. Molecular dynamics (MD) simulations were performed to understand the mechanisms by which the estrogenic compounds bind to and activate the estrogen receptor (ER). Forty-five BPA replacement compounds were identified in the literature. Seven were more estrogenic and five less estrogenic than BPA, while six were nonestrogenic in EADB. A two-tier in silico model was developed based on molecular docking to predict the estrogenic activity of the 27 compounds lacking data. Eleven were predicted as ER binders and 16 as nonbinders. MD simulations revealed hydrophobic contacts and hydrogen bonds as the main interactions between ER and the estrogenic compounds.
authors: Division of Bioinformatics and Biostatistics, National Center for Toxicological Research, U.S. Food and Drug Administration , 3900 NCTR Road, Jefferson, Arkansas 72079, United States.
authors: Hui Wen
authors: HW
authors: Ng
authors: Division of Bioinformatics and Biostatistics, National Center for Toxicological Research, U.S. Food and Drug Administration , 3900 NCTR Road, Jefferson, Arkansas 72079, United States.
authors: Mao
authors: M
authors: Shu
authors: Division of Bioinformatics and Biostatistics, National Center for Toxicological Research, U.S. Food and Drug Administration , 3900 NCTR Road, Jefferson, Arkansas 72079, United States.
authors: Heng
authors: H
authors: Luo
authors: Division of Bioinformatics and Biostatistics, National Center for Toxicological Research, U.S. Food and Drug Administration , 3900 NCTR Road, Jefferson, Arkansas 72079, United States.
authors: Hao
authors: H
authors: Ye
authors: Division of Bioinformatics and Biostatistics, National Center for Toxicological Research, U.S. Food and Drug Administration , 3900 NCTR Road, Jefferson, Arkansas 72079, United States.
authors: Weigong
authors: W
authors: Ge
authors: Division of Bioinformatics and Biostatistics, National Center for Toxicological Research, U.S. Food and Drug Administration , 3900 NCTR Road, Jefferson, Arkansas 72079, United States.
authors: Roger
authors: R
authors: Perkins
authors: Division of Bioinformatics and Biostatistics, National Center for Toxicological Research, U.S. Food and Drug Administration , 3900 NCTR Road, Jefferson, Arkansas 72079, United States.
authors: Weida
authors: W
authors: Tong
authors: Division of Bioinformatics and Biostatistics, National Center for Toxicological Research, U.S. Food and Drug Administration , 3900 NCTR Road, Jefferson, Arkansas 72079, United States.
authors: Huixiao
authors: H
authors: Hong
mesh_terms: D001559:Benzhydryl Compounds / Q000633:toxicity*; D003198:Computer Simulation; D062126:Databases, Chemical; D052244:Endocrine Disruptors / Q000633:toxicity*; D004967:Estrogens / Q000494:pharmacology*; D056004:Molecular Dynamics Simulation; D010636:Phenols / Q000633:toxicity*; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D052244:Endocrine Disruptors; D004967:Estrogens; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds