Elucidating the Aryl Hydrocarbon Receptor Antagonism from a Chemical-Structural Perspective

[en] The aryl hydrocarbon receptor (AhR) plays an important role in several biological processes such as reproduction, immunity and homoeostasis. However, little is known on the chemical-structural and physicochemical features that influence the activity of AhR antagonistic modulators. In the present report, in vitro AhR antagonistic activity evaluations, based on a chemical-activated luciferase gene expression (AhR-CALUX) bioassay, and an extensive literature review were performed with the aim of constructing a structurally diverse database of contaminants and potentially toxic chemicals. Subsequently, QSAR models based on Linear Discriminant Analysis and Logistic Regression, as well as two toxicophoric hypotheses were proposed to model the AhR antagonistic activity of the built dataset. The QSAR models were rigorously validated yielding satisfactory performance for all classification parameters. Likewise, the toxicophoric hypotheses were validated using a diverse set of 350 decoys, demonstrating adequate robustness and predictive power. Chemical interpretations of both the QSAR and toxicophoric models suggested that hydrophobic constraints, the presence of aromatic rings and electron-acceptor moieties are critical for the AhR antagonism. Therefore, it is hoped that the deductions obtained in the present study will contribute to elucidate further on the structural and physicochemical factors influencing the AhR antagonistic activity of chemical compounds.

Research center :

CART - Centre Interfacultaire d'Analyse des Résidus en Traces - ULiège

Disciplines :

Biochemistry, biophysics & molecular biology

Author, co-author :

Goya-Jorge, Elizabeth

Doan Thi Que ; Université de Liège - ULiège > Form. doct. sc. (bioch., biol. mol. cel., bioinf. - paysage)

Scippo, Marie-Louise ; Université de Liège - ULiège > Département de sciences des denrées alimentaires (DDA) > Analyse des denrées alimentaires

Muller, Marc ; Université de Liège - ULiège > Département des sciences de la vie > I3-Laboratory for Organogenesis and Regeneration

Giner, Rosa

Barigye, Sephen

Gozalbes, Rafael

Language :

English

Title :

Elucidating the Aryl Hydrocarbon Receptor Antagonism from a Chemical-Structural Perspective

Publication date :

09 January 2020

Journal title :

SAR and QSAR in Environmental Research

ISSN :

1062-936X

eISSN :

1029-046X

Publisher :

Taylor & Francis, United Kingdom

Volume :

Issue :

Pages :

209-226

Peer reviewed :

Peer Reviewed verified by ORBi

Additional URL :

https://www.tandfonline.com/eprint/7J83XDZVPIKUYQERRJQA/full?target=10.1080/1062936X.2019.1708460

European Projects :

H2020 - 722634 - PROTECTED - PROTECTion against Endocrine Disruptors; Detection, mixtures, health effects, risk assessment and communication.

Name of the research project :

PROTECTED

Funders :

CE - Commission Européenne [BE]
Union Européenne [BE]

Funding number :

722634

Funding text :

This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No. 722634.

Data Set :

Supplementary material

Available on ORBi :

since 10 February 2020

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