In silico approach to identify potential thyroid hormone disruptors among currently known dust contaminants and their metabolites

J. Zhang; J.H. Kamstra; M. Ghorbanzadeh; J.M. Weiss; T. Hamers; P.L. Andersson

doi:10.1021/acs.est.5b01742

In silico approach to identify potential thyroid hormone disruptors among currently known dust contaminants and their metabolites

J. Zhang, J.H. Kamstra, M. Ghorbanzadeh, J.M. Weiss, T. Hamers, P.L. Andersson

Chemistry and Biology

Research output: Contribution to Journal › Article › Academic › peer-review

Abstract

Thyroid hormone disrupting chemicals (THDCs) interfere with the thyroid hormone system and may induce multiple severe physiological disorders. Indoor dust ingestion is a major route of THDCs exposure in humans, and one of the molecular targets of these chemicals is the hormone transporter transthyretin (TTR). To virtually screen indoor dust contaminants and their metabolites for THDCs targeting TTR, we developed a quantitative structure-activity relationship (QSAR) classification model. The QSAR model was applied to an in-house database including 485 organic dust contaminants reported from literature data and their 433 in silico derived metabolites. The model predicted 37 (7.6%) dust contaminants and 230 (53.1%) metabolites as potential TTR binders. Four new THDCs were identified after testing 23 selected parent dust contaminants in a radio-ligand TTR binding assay; 2,2′,4,4′-tetrahydroxybenzophenone, perfluoroheptanesulfonic acid, 3,5,6-trichloro-2-pyridinol, and 2,4,5-trichlorophenoxyacetic acid. These chemicals competitively bind to TTR with 50% inhibition (IC

Original language	English
Pages (from-to)	10099-10107
Journal	Environmental Science and Technology
Volume	49
DOIs	https://doi.org/10.1021/acs.est.5b01742
Publication status	Published - 2015

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Zhang, J., Kamstra, J. H., Ghorbanzadeh, M., Weiss, J. M., Hamers, T., & Andersson, P. L. (2015). In silico approach to identify potential thyroid hormone disruptors among currently known dust contaminants and their metabolites. Environmental Science and Technology, 49, 10099-10107. https://doi.org/10.1021/acs.est.5b01742

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title = "In silico approach to identify potential thyroid hormone disruptors among currently known dust contaminants and their metabolites",

abstract = "Thyroid hormone disrupting chemicals (THDCs) interfere with the thyroid hormone system and may induce multiple severe physiological disorders. Indoor dust ingestion is a major route of THDCs exposure in humans, and one of the molecular targets of these chemicals is the hormone transporter transthyretin (TTR). To virtually screen indoor dust contaminants and their metabolites for THDCs targeting TTR, we developed a quantitative structure-activity relationship (QSAR) classification model. The QSAR model was applied to an in-house database including 485 organic dust contaminants reported from literature data and their 433 in silico derived metabolites. The model predicted 37 (7.6{\%}) dust contaminants and 230 (53.1{\%}) metabolites as potential TTR binders. Four new THDCs were identified after testing 23 selected parent dust contaminants in a radio-ligand TTR binding assay; 2,2′,4,4′-tetrahydroxybenzophenone, perfluoroheptanesulfonic acid, 3,5,6-trichloro-2-pyridinol, and 2,4,5-trichlorophenoxyacetic acid. These chemicals competitively bind to TTR with 50{\%} inhibition (IC",

author = "J. Zhang and J.H. Kamstra and M. Ghorbanzadeh and J.M. Weiss and T. Hamers and P.L. Andersson",

year = "2015",

doi = "10.1021/acs.est.5b01742",

language = "English",

volume = "49",

pages = "10099--10107",

journal = "Environmental Science and Technology",

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In silico approach to identify potential thyroid hormone disruptors among currently known dust contaminants and their metabolites. / Zhang, J.; Kamstra, J.H.; Ghorbanzadeh, M.; Weiss, J.M.; Hamers, T.; Andersson, P.L.

In: Environmental Science and Technology, Vol. 49, 2015, p. 10099-10107.

Research output: Contribution to Journal › Article › Academic › peer-review

TY - JOUR

T1 - In silico approach to identify potential thyroid hormone disruptors among currently known dust contaminants and their metabolites

AU - Zhang, J.

AU - Kamstra, J.H.

AU - Ghorbanzadeh, M.

AU - Weiss, J.M.

AU - Hamers, T.

AU - Andersson, P.L.

PY - 2015

Y1 - 2015

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AB - Thyroid hormone disrupting chemicals (THDCs) interfere with the thyroid hormone system and may induce multiple severe physiological disorders. Indoor dust ingestion is a major route of THDCs exposure in humans, and one of the molecular targets of these chemicals is the hormone transporter transthyretin (TTR). To virtually screen indoor dust contaminants and their metabolites for THDCs targeting TTR, we developed a quantitative structure-activity relationship (QSAR) classification model. The QSAR model was applied to an in-house database including 485 organic dust contaminants reported from literature data and their 433 in silico derived metabolites. The model predicted 37 (7.6%) dust contaminants and 230 (53.1%) metabolites as potential TTR binders. Four new THDCs were identified after testing 23 selected parent dust contaminants in a radio-ligand TTR binding assay; 2,2′,4,4′-tetrahydroxybenzophenone, perfluoroheptanesulfonic acid, 3,5,6-trichloro-2-pyridinol, and 2,4,5-trichlorophenoxyacetic acid. These chemicals competitively bind to TTR with 50% inhibition (IC

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M3 - Article

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