QSAR models of the in vitro estrogen activity of bisphenol A analogs

Bisphenol A is a monomer constituent of epoxy and polycarbonate resins used in consumer products. Many studies have shown that bisphenol A is a weak estrogen receptor agonist with endocrine disrupting potential in exposed organisms. Presented here is a series of quantitative structure-activity relationship models to describe the in vitro hormone activity (estrogen receptor binding, reporter gene induction, and cell proliferation) of bisphenol A and 24 of its analogs. The hormone activity ranged over four orders of magnitude, with bisphenol A displaying intermediate activity. Comparative molecular field analysis, comparative molecular similarity indices, and hologram quantitative structure activity models were generated using SYBYL 6.8. Bisphenols with optimal estrogen activity contained two unencumbered phenolic groups in the para orientation, and multiple alkyl substituents extending from the carbon linking phenolic rings. Bisphenols with methyl group hydrogens replaced by halogens also produced strong estrogenic analogs. These studies suggest that it may be possible to use such structure activities to develop bisphenols that are useful monomers with reduced hormone activity.