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

Nowak, Karolina (author), Jakopin, Žiga (author)

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.

• Language: English
• Keywords: BPA, BPA analogues, halogenated bisphenols, nuclear receptors, endocrine disruption, in silico
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: FFA - Faculty of Pharmacy
• Publication status: Published
• Publication version: Version of Record
• Year: 2023
• Number of pages: 12 str.
• Numbering: Vol. 173, art. 113623
• PID: 20.500.12556/RUL-148309-8d21348f-c78d-ef65-1ed3-d25bfffe1452
• UDC: 612.43:620.266.1
• ISSN on article: 1873-6351
• DOI: 10.1016/j.fct.2023.113623
• COBISS.SI-ID: 138155779
• Publication date in RUL: 11.08.2023

Record is a part of a journal

• Title: Food and chemical toxicology
• Publisher: Elsevier
• ISSN: 1873-6351
• COBISS.SI-ID: 4308780

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.

Secondary language

• Language: Slovenian
• Keywords: BPA analogi, halogenirani bisfenoli, nuklearni receptorji, endokrine motnje, in silico, endokrinologija

Projects

• Funder: ARRS - Slovenian Research Agency
• Project number: P1-0420
• Name: Napredna imunološka zdravila in celični pristopi v farmaciji

• Funder: Other - Other funder or multiple funders
• Funding programme: European Federation of Immunological Societies-Immunology Letters, Short-Term Fellowship