Endocrine disruptive potential of a new bisphenol A substitute DD-70

Abstract (English)

The increasing number of evidences about the endocrine disruptive effects of bisphenol A (BPA) have led to its
replacement with insufficiently explored structural alternatives. DD-70 (1,7-bis (4-hydroxyphenylthio)-3, 5-
dioxaheptane) belongs to the novel BPA substitutes mainly found in thermal paper. Having bisphenol structure,
DD-70 could have the similar estrogenic profile as BPA. Hence, the aim of this study was to investigate the endocrine disruptive potential of this compound using in silico tools. SwissADME was used for the calculation of molecular properties and the prediction of gastrointestinal absorption of DD-70 whereas GOLD software was applied for molecular docking. The binding affinity of DD-70 towards estrogen receptor alpha (ERα, pdb: 7UJO), beta (ERβ, pdb: 5TOA) and gamma (ERγ, pdb: 6KNR) was evaluated in comparison to BPA using ChemPLP as a scoring function. Based on the analyzed molecular properties, DD-70 met Lipinski's rule of five criteria for good oral bioavailability as well Veber`s rule with predicted high gastrointestinal absorption. The obtained ChemPLP scores of DD-70 for ERα, ERβ, and ERγ were 83.92, 71.04, and 73.28, respectively, in comparison to co-crystallized ligand scores of 99.97 (ERα), 67.46 (ERβ), and 116.35 (ERγ). However, when compared with the ChemPLP scores obtained for BPA (ERα 60.36, ERβ 55.54, and ERγ 59.83), DD-70 had much higher binding affinity. The obtained results suggest DD-70 high potential for impairment of normal estrogen signaling through the interactions with estrogen receptors. In silico results imply health risks associated with the exposure to DD-70 as xenoestrogen. Both in vitro and in vivo studies are needed in order to better understand the endocrine disruptive potential of this new BPA alternative.