635
Views
11
CrossRef citations to date
0
Altmetric
Articles

Elucidating the aryl hydrocarbon receptor antagonism from a chemical-structural perspective

ORCID Icon, , , , , & show all
Pages 209-226 | Received 09 Nov 2019, Accepted 19 Dec 2019, Published online: 09 Jan 2020
 

ABSTRACT

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.

Disclosure statement

No potential conflict of interest was reported by the authors.

Supplementary material

Supplementary material for this article can be accessed at: https://doi.org/10.1080/1062936X.2019.1708460.

Additional information

Funding

This work was developed by the Innovative Training Network ‘PROTECTED’: PROTECTion against Endocrine Disruptors; Detection, mixtures, health effects, risk assessment and communication. The project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie actions (MSCA) with grant agreement No. 722634.

Log in via your institution

Log in to Taylor & Francis Online

PDF download + Online access

  • 48 hours access to article PDF & online version
  • Article PDF can be downloaded
  • Article PDF can be printed
USD 61.00 Add to cart

Issue Purchase

  • 30 days online access to complete issue
  • Article PDFs can be downloaded
  • Article PDFs can be printed
USD 543.00 Add to cart

* Local tax will be added as applicable

Related Research

People also read lists articles that other readers of this article have read.

Recommended articles lists articles that we recommend and is powered by our AI driven recommendation engine.

Cited by lists all citing articles based on Crossref citations.
Articles with the Crossref icon will open in a new tab.