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Future Med Chem. 2013 Oct;5(16):1993-2006. doi: 10.4155/fmc.13.159.

Targeting the redox metabolism of Plasmodium falciparum.

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Université de Toulouse, UPS; PHARMA-DEV (UMR 152); F-31062 Toulouse cedex 9, France.


Targeting the redox metabolism of Plasmodium falciparum to create a fatal overload of oxidative stress is a route to explore the discovery of new antimalarial drugs. There are three main possibilities to target the redox metabolism of P. falciparum at the erythrocytic stage: selective targeting and inhibition of a redox P. falciparum protein or enzyme; oxidant drugs targeting essential parasite components and heme by-products; and redox cycler drugs targeting the parasitized red blood cell. Oxidants and redox cycler agents, with or without specific targets, may disrupt the fragile parasitized erythrocyte redox-dependent architecture given that: redox equilibrium plays a vital role at the erythrocytic stage; P. falciparum possesses major NADPH-dependent redox systems, such as glutathione and thioredoxin ones; and the protein-NADPH-dependent phosphorylation-dephosphorylation process is involved in building new permeation pathways and channels for the nutrient-waste import-export traffic of the parasite.

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