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New insights into ethionamide metabolism: influence of oxidized methionine on its degradation path

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Abstract

Ethionamide (ETH) is a commercial drug, used as a second-line resource to neutralize Mycobacterium tuberculosis infections. It is proven that its metabolization in the organism leads to the formation of the active form of the drug, but some metabolic pathways may lead to the loss of its activity. Our work proved that the presence of oxidized methionine in cells could influence ETH's degradation, leading to the appearance of an inactive metabolite that is detectable by HPLC and mass spectrometry. In addition, it was found this process increases with the degree of methionine oxidation. This study contributes to a better understanding of ethionamide's metabolism in living organisms, and can help in the design of new drugs or ethionamide boosters for the combat of multidrug resistant tuberculosis.

Graphical abstract: New insights into ethionamide metabolism: influence of oxidized methionine on its degradation path

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Article information


Submitted
20 Jul 2020
Accepted
17 Sep 2020
First published
29 Sep 2020

RSC Med. Chem., 2020, Advance Article
Article type
Research Article

New insights into ethionamide metabolism: influence of oxidized methionine on its degradation path

N. Vale, D. Duarte, A. Correia, C. Alves, P. Figueiredo and H. A. Santos, RSC Med. Chem., 2020, Advance Article , DOI: 10.1039/D0MD00253D

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