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

Logo poskytovatele
Logo poskytovatele
Logo poskytovatele

Varování

Publikace nespadá pod Ústav výpočetní techniky, ale pod Přírodovědeckou fakultu. Oficiální stránka publikace je na webu muni.cz.
Autoři

KÜHNE Ralph HILSCHEROVÁ Klára SMUTNÁ Marie LEßMÖLLMANN Friederike SCHÜÜRMANN Gerrit

Rok publikování 2024
Druh Článek v odborném periodiku
Časopis / Zdroj Chemosphere
Fakulta / Pracoviště MU

Přírodovědecká fakulta

Citace
www https://doi.org/10.1016/j.chemosphere.2023.140611
Doi http://dx.doi.org/10.1016/j.chemosphere.2023.140611
Klíčová slova Absorption; Bioavailability; Blood/brain partitioning; In silico assessment; Penetration; Permeation; Retinoid; Thyroid hormone disruptors
Popis 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.
Související projekty:

Používáte starou verzi internetového prohlížeče. Doporučujeme aktualizovat Váš prohlížeč na nejnovější verzi.

Další info