Por favor, use este identificador para citar o enlazar este documento: https://hdl.handle.net/2445/191713
Título: Characterization of domiphen bromide as a new fast-acting antiplasmodial agent inhibiting the apicoplastidic methyl erythritol phosphate pathway.
Autor: Biosca, Arnau
Ramírez, Miriam
Gomez-Gomez, Alex
Lafuente, Aritz
Iglesias, Valentín
Pozo, Oscar J.
Imperial Ródenas, Santiago
Fernàndez Busquets, Xavier
Materia: Malària
Plasmodium falciparum
Medicaments antipalúdics
Antibiòtics
Malaria
Plasmodium falciparum
Antimalarials
Antibiotics
Fecha de publicación: 22-jun-2022
Publicado por: MDPI
Resumen: The evolution of resistance by the malaria parasite to artemisinin, the key component of the combination therapy strategies that are at the core of current antimalarial treatments, calls for the urgent identification of new fast-acting antimalarials. The apicoplast organelle is a preferred target of antimalarial drugs because it contains biochemical processes absent from the human host. Fosmidomycin is the only drug in clinical trials targeting the apicoplast, where it inhibits the methyl erythritol phosphate (MEP) pathway. Here, we characterized the antiplasmodial activity of domiphen bromide (DB), another MEP pathway inhibitor with a rapid mode of action that arrests the in vitro growth of Plasmodium falciparum at the early trophozoite stage. Metabolomic analysis of the MEP pathway and Krebs cycle intermediates in 20 µM DB-treated parasites suggested a rapid activation of glycolysis with a concomitant decrease in mitochondrial activity, consistent with a rapid killing of the pathogen. These results present DB as a model compound for the development of new, potentially interesting drugs for future antimalarial combination therapies.
Nota: Reproducció del document publicat a: https://doi.org/10.3390/pharmaceutics14071320
Es parte de: Pharmaceutics, 2022, vol. 14, num. 7, p. 1320
URI: https://hdl.handle.net/2445/191713
Recurso relacionado: https://doi.org/10.3390/pharmaceutics14071320
ISSN: 1999-4923
Aparece en las colecciones:Articles publicats en revistes (Bioquímica i Biomedicina Molecular)

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