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2022_Pharmaceutics_Characterization_FernandezBusquetsX.pdf (3.04 MB)

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2022-06-22

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cc by (c) Arnau Biosca et al., 2022
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/189045

Characterization of Domiphen Bromide as a New Fast-Acting Antiplasmodial Agent Inhibiting the Apicoplastidic Methyl Erythritol Phosphate Pathway

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https://doi.org/10.3390/pharmaceutics14071320

Resum

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 mu M 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.

Matèries

Plasmodium falciparum, Malària, Antibiòtics

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Plasmodium falciparum, Malaria, Antibiotics

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Articles publicats en revistes (Institut de Bioenginyeria de Catalunya (IBEC))

Citació

BIOSCA, Arnau, RAMIREZ, Miriam, GOMEZ GOMEZ, Alex, LAFUENTE, Aritz, IGLESIAS, Valentín, POZO, Oscar j., IMPERIAL RÓDENAS, Santiago, FERNÀNDEZ BUSQUETS, Xavier. Characterization of Domiphen Bromide as a New Fast-Acting Antiplasmodial Agent Inhibiting the Apicoplastidic Methyl Erythritol Phosphate Pathway. _Pharmaceutics_. 2022. Vol. 14, núm. 7. [consulta: 21 de gener de 2026]. ISSN: 1999-4923. [Disponible a: https://hdl.handle.net/2445/189045]

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