The Potential Interaction of Ethionamide-Thyroid Hormone Receptor Induces Hypothyroidism

Lesmana, Ronny and Shidqi, Firyali Rahmani and Goenawan, Hanna and Setiawan, Iwan and Gondokesumo, Marisca Evalina and Suhud, Farida and Wathoni, Nasrul (2021) The Potential Interaction of Ethionamide-Thyroid Hormone Receptor Induces Hypothyroidism. Pharmacognosy Journal, 13 (5). pp. 1174-1179. ISSN 0975-3575

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Hypothyroidism is a common side effect found in patients with multidrug-resistant tuberculosis taking ethionamide. The mechanism of ethionamide-induced hypothyroidism is potentially caused by the structure of ethionamide compounds chemically similar to thioamide, such as propylthiouracil (C7H8N2S), which inhibits thyroid hormone synthesis. However, hypothyroidism is caused not only by a lack of production but also by signaling alteration. Thyroid hormone action is mediated by thyroid hormone receptors (TRs), members of the nuclear receptor superfamily that regulate their target genes. Unfortunately, there are limited studies on the potential interaction of ethionamide with TRs. Objective: In the present study, we want to elaborate on the potential interaction of ethionamide with TRs which might alter the thyroid hormone genomic regulation. Methods: Molecular docking studies were used to evaluate the potential interaction between ethionamide with TRα and TRβ. Results: The molecular docking results on TRα showed more than one hydrogen bond–steric interaction formed from the ethionamide–amino acid residue interaction. Ethionamide–TRβ interaction showed more than one steric interaction, but the hydrogen bonds are not visualized. The docking score between ethionamide and TRα is −7.373 kcal/ mol and higher than its interaction with TRβ. Conclusion: These findings indicate that ethionamide can interact with TRα and TRβ. However, the ethionamide–TRα interaction is stronger than ethionamide–TRβ interaction. Our study reports a novel mechanism of action of ethionamide-induced hypothyroidism.

Item Type: Article
Uncontrolled Keywords: Ethionamide, Hypothyroidism, Molecular docking, TRα, TRβ
Subjects: R Medicine > R Medicine (General)
R Medicine > RM Therapeutics. Pharmacology
R Medicine > RS Pharmacy and materia medica
R Medicine > RZ Other systems of medicine
Divisions: Faculty of Pharmacy > Department of Pharmacy
Date Deposited: 11 Jan 2022 04:30
Last Modified: 11 Jan 2022 04:30

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