PFAS (per- and polyfluorinated alkyl substances) as EDCs (endocrine-disrupting chemicals) - Identification of compounds with high potential to bind to selected terpenoids NHRs (nuclear hormone receptors)

• Published in: Chemosphere (Oxford) 2024-12, Vol.370, p.143967
• Main Authors: Buławska, Natalia, Sosnowska, Anita, Kowalska, Dominika, Stępnik, Maciej, Puzyn, Tomasz
• Format: Article
• Language: English
• ISSN: 1879-1298; 1879-1298
• DOI: 10.1016/j.chemosphere.2024.143967

The objective of the subsequent study was to examine the probability of PFAS (per- and polyfluorinated alkyl substances) binding to various NHRs (nuclear hormone receptors) and to identify their structural features that contribute most to the binding score (BS). We evaluated the BS for PFAS in relation to 7 selected NHRs - 4 with additional antagonist forms (Retinoid X receptor alpha - RXRα, Liver X receptor alpha - LXRα, Liver X receptor beta - LXRβ, Estrogen receptor alpha - ERα, Estrogen receptor alpha antagonist - anti-ERα, Estrogen receptor beta - ERβ, Estrogen receptor beta antagonist - anti-ERβ, Glucocorticoid receptor - GR, Glucocorticoid receptor antagonist - anti-GR, Androgen receptor - AR, Androgen receptor antagonist - anti-AR). We based our study on the results of molecular docking, which we used to develop MLR-QSAR (Multiple Linear Regression - Quantitative Structure-Activity Relationship) models. The models we developed allowed us to predict the BS for an extensive set of PFAS compounds from the NORMAN database (more than 4,000) - virtual screening. The probability of PFAS binding to selected receptors was determined by structural features such as particle size, branching, and fluorine content. These variables were also identified in the literature reports of experimental studies as the most important for this group of compounds. The research focused on receptors from the terpenoid group. The RXRα, LXRα and β, GR, and anti-GR receptors were shown to be the group less likely to be affected by PFAS. Sex hormones such as AR, anti-AR, ERα and ERβ with their antagonist forms are the most affected.