Predictive insight into the relationship between AhR binding property and toxicity of polybrominated diphenyl ethers by PLS-derived QSAR

Chenggang Gu, Mohammad Goodarzi, Xinglun Yang, Yongrong Bian, Cheng Sun, Xin Jiang

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

Polybrominated diphenyl ethers (PBDEs) are experimentally indicated to be capable of binding to the cytosolic aryl hydrocarbon receptor (AhR) and show a weak or moderate toxicity. However, little is yet known about the AhR-mediated toxicology. To fully evaluate the structural effects of PBDE ligand on AhR binding affinity and toxicity, quantitative structure-activity relationships (QSARs) were developed by PLS analysis. In this study, a simple but potent QSAR that was qualified with much better or comparable performance of prediction was optimally established for PBDE toxicity. With QSAR analysis, the AhR binding property was carefully described to reflect the origin of AhR binding affinity. Besides the effects from topological characters, the dispersion and electrostatic interactions were of indispensability for AhR binding affinity whereas the dispersion was further suggested to be dominant. The structural requirement for AhR binding affinity and toxicity was also investigated. As was similarly observed for polychlorinated biphenyls (PCBs), the preferential bromination at para- and meta (particularly 3,3'-)-sites was confirmed as a key determinant to improve the AhR binding affinity and the toxicity of PBDEs.

Original languageEnglish (US)
Pages (from-to)269-274
Number of pages6
JournalToxicology Letters
Volume208
Issue number3
DOIs
Publication statusPublished - Feb 5 2012

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Keywords

  • AhR binding affinity
  • DFT
  • PLS
  • Polybrominated diphenyl ether
  • Toxicity
  • WHIM

ASJC Scopus subject areas

  • Toxicology

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