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New insights into ethionamide metabolism: influence of oxidized methionine on its degradation path
Nuno Vale1,2, Diana Duarte1,3, Alexandra Correia4
1OncoPharma Research Group, Center for Health Technology and Services Research (CINTESIS) Rua Dr. Plácido da Costa 4200-450 Porto Portugal.
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.
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