In silico bioavailability triggers applied to direct and
indirect thyroid hormone disruptors

Přehled o publikaci

J 2024

In silico bioavailability triggers applied to direct and indirect thyroid hormone disruptors

KÜHNE, Ralph; Klára HILSCHEROVÁ; Marie SMUTNÁ; Friederike LESSMÖLLMANN; Gerrit SCHÜÜRMANN et al.

Basic information

Original name

In silico bioavailability triggers applied to direct and indirect thyroid hormone disruptors

Authors

KÜHNE, Ralph; Klára HILSCHEROVÁ; Marie SMUTNÁ; Friederike LESSMÖLLMANN and Gerrit SCHÜÜRMANN

Edition

Chemosphere, OXFORD, PERGAMON-ELSEVIER SCIENCE LTD, 2024, 0045-6535

Other information

Language

English

Type of outcome

Article in a journal

Country of publisher

United Kingdom of Great Britain and Northern Ireland

Confidentiality degree

is not subject to a state or trade secret

References:

URL

Marked to be transferred to RIV

Yes

RIV identification code

RIV/00216224:14310/24:00139261

Organization

Přírodovědecká fakulta – Repository – Repository

DOI

https://doi.org/10.1016/j.chemosphere.2023.140611

EID Scopus

2-s2.0-85178038315

Keywords in English

Absorption; Bioavailability; Blood/brain partitioning; In silico assessment; Penetration; Permeation; Retinoid; Thyroid hormone disruptors

Links

825753, interní kód Repo. 857560, interní kód Repo.

Changed: 31/7/2025 00:50, RNDr. Daniel Jakubík

Abstract

In the original language

Among endocrine disruption, interference with the thyroid hormone (TH) regulation is of increasing concern. Respective compounds encode through their structural features both the potential for TH disruption, and the bioavailability mitigating the toxicological effect. The aim of this study is to provide a substructure-based screening-level QSAR (quantitative structure-activity relationship) that discriminates bioavailable TH disruptors from not bioavailable counterparts, covering both direct and indirect (retinoid- and AhR-mediated) modes of action. The QSAR has been derived from literature data for 1642 compounds, and takes into account Lipinski's rule-of-five and the brain/blood partition coefficient Kbrain/blood. For its validation, an external test set of 145 substances has been used. For 1787 compounds meeting the model application domain, the model yields only one false negative. The discussion addresses the mechanistic meaning of the bioavailability triggers molecular weight, H-bond donor and acceptor, hydrophobicity (log Kow), and the physicochemical properties underlying log Kbrain/blood. The model may serve as bioavailability-screening step within a decision support system for the predictive assessment of chemicals regarding their potential to disrupt thyroid hormone function in a direct or indirect manner.

Files attached

https://is.muni.cz/publication/2488319/2488319.pdf

Cite

KÜHNE, Ralph; Klára HILSCHEROVÁ; Marie SMUTNÁ; Friederike LESSMÖLLMANN and Gerrit SCHÜÜRMANN. In silico bioavailability triggers applied to direct and indirect thyroid hormone disruptors. Chemosphere. OXFORD: PERGAMON-ELSEVIER SCIENCE LTD, 2024, vol. 348, January, p. 1-10. ISSN 0045-6535. Available from: https://doi.org/10.1016/j.chemosphere.2023.140611.

@article{78546,
   author = {Kühne, Ralph and Hilscherová, Klára and Smutná, Marie and Leßmöllmann, Friederike and Schüürmann, Gerrit},
   article_location = {OXFORD},
   article_number = {January},
   doi = {https://doi.org/10.1016/j.chemosphere.2023.140611},
   keywords = {Absorption; Bioavailability; Blood/brain partitioning; In silico assessment; Penetration; Permeation; Retinoid; Thyroid hormone disruptors},
   language = {eng},
   issn = {0045-6535},
   journal = {Chemosphere},
   title = {In silico bioavailability triggers applied to direct and indirect thyroid hormone disruptors},
   url = {https://doi.org/10.1016/j.chemosphere.2023.140611},
   volume = {348},
   year = {2024}
}

TY  - JOUR
ID  - 78546
AU  - Kühne, Ralph - Hilscherová, Klára - Smutná, Marie - Leßmöllmann, Friederike - Schüürmann, Gerrit
PY  - 2024
TI  - In silico bioavailability triggers applied to direct and indirect thyroid hormone disruptors
JF  - Chemosphere
VL  - 348
IS  - January
SP  - 1-10
EP  - 1-10
PB  - PERGAMON-ELSEVIER SCIENCE LTD
SN  - 0045-6535
KW  - Absorption
KW  - Bioavailability
KW  - Blood/brain partitioning
KW  - In silico assessment
KW  - Penetration
KW  - Permeation
KW  - Retinoid
KW  - Thyroid hormone disruptors
UR  - https://doi.org/10.1016/j.chemosphere.2023.140611
N2  - Among endocrine disruption, interference with the thyroid hormone (TH) regulation is of increasing concern. Respective compounds encode through their structural features both the potential for TH disruption, and the bioavailability mitigating the toxicological effect. The aim of this study is to provide a substructure-based screening-level QSAR (quantitative structure-activity relationship) that discriminates bioavailable TH disruptors from not bioavailable counterparts, covering both direct and indirect (retinoid- and AhR-mediated) modes of action. The QSAR has been derived from literature data for 1642 compounds, and takes into account Lipinski's rule-of-five and the brain/blood partition coefficient Kbrain/blood. For its validation, an external test set of 145 substances has been used. For 1787 compounds meeting the model application domain, the model yields only one false negative. The discussion addresses the mechanistic meaning of the bioavailability triggers molecular weight, H-bond donor and acceptor, hydrophobicity (log Kow), and the physicochemical properties underlying log Kbrain/blood. The model may serve as bioavailability-screening step within a decision support system for the predictive assessment of chemicals regarding their potential to disrupt thyroid hormone function in a direct or indirect manner.
ER  -

KÜHNE, Ralph; Klára HILSCHEROVÁ; Marie SMUTNÁ; Friederike LESSMÖLLMANN and Gerrit SCHÜÜRMANN. In silico bioavailability triggers applied to direct and indirect thyroid hormone disruptors. \textit{Chemosphere}. OXFORD: PERGAMON-ELSEVIER SCIENCE LTD, 2024, vol.~348, January, p.~1-10. ISSN~0045-6535. Available from: https://doi.org/10.1016/j.chemosphere.2023.140611.

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