In silico profiling of endocrine-disrupting potential of bisphenol analogues and their halogenated transformation products

Karolina Nowak (Author), Žiga Jakopin (Author)

Abstract

Due to its endocrine-disrupting properties, bisphenol A (BPA) is being phased out from plastics, thermal paper and epoxy resins, and its replacements are being introduced into the market. Bisphenols are released into the environment, where they can undergo halogenation. Unlike BPA, the endocrine-disrupting potential of BPA analogues and their halogenated transformation products has not been extensively studied. The aim of this study was to evaluate the endocrine-disrupting potential of 18 BPA analogues and their halogenated derivatives by calculating affinities for 14 human nuclear receptors utilizing the Endocrine Disruptome and VirtualToxLab™ in silico tools. Our simulations identified AR, ERs, and GR as the most favorable targets of bisphenols and their derivatives. Several BPA analogues displayed a higher predicted potential for endocrine disruption than BPA. Our models highlighted BPZ and BPPH as the most hazardous in terms of predicted endocrine activities. Halogenation, in general, was predicted to increase the binding affinity of bisphenols for AR, ERβ, MR, GR, PPARγ, and TRβ. Notably, mono- or 2,2′-di-halogenated bisphenols exhibited the highest potential for endocrine disruption. In vitro corroboration of the obtained results should be the next milestone in evaluating the safety of BPA substitutes and their halogenated transformation products.

Keywords

BPA;BPA analogues;halogenated bisphenols;nuclear receptors;endocrine disruption;in silico;

Data

Language:	English
Year of publishing:	2023
Typology:	1.01 - Original Scientific Article
Organization:	UL FFA - Faculty of Pharmacy
UDC:	612.43:620.266.1
COBISS:	138155779
ISSN:	1873-6351
Views:	27
Downloads:	4
Average score:	0 (0 votes)
Metadata:

Other data

Secondary language:	Slovenian
Secondary keywords:	BPA analogi;halogenirani bisfenoli;nuklearni receptorji;endokrine motnje;in silico;Endokrinologija;
Type (COBISS):	Article
Pages:	Str. 1-12
Volume:	ǂVol. ǂ173
Issue:	ǂ iss.ǂ, [article no.] 113623
Chronology:	2023
DOI:	10.1016/j.fct.2023.113623
ID:	19782104