Drug Screen Targeted at Plasmodium Liver Stages Identifies a Potent Multistage Antimalarial Drug

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Author
da Cruz, Filipa P.
Martin, Cécilie
Lafuente-Monasterio, Maria J.
Rodrigues, Tiago
Sönnichsen, Birte
Moreira, Rui
Gamo, Francisco-Javier
Hannus, Michael
Prudêncio, Miguel
Note: Order does not necessarily reflect citation order of authors.
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https://doi.org/10.1093/infdis/jis184Metadata
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da Cruz, Filipa P., Cécilie Martin, Kathrin Buchholz, Maria J. Lafuente-Monasterio, Tiago Rodrigues, Birte Sönnichsen, Rui Moreira, et al. 2012. Drug screen targeted at plasmodium liver stages identifies a potent multistage antimalarial drug. The Journal of Infectious Diseases 205(8): 1278-1286.Abstract
Plasmodium parasites undergo a clinically silent and obligatory developmental phase in the host’s liver cells before they are able to infect erythrocytes and cause malaria symptoms. To overcome the scarcity of compounds targeting the liver stage of malaria, we screened a library of 1037 existing drugs for their ability to inhibit Plasmodium hepatic development. Decoquinate emerged as the strongest inhibitor of Plasmodium liver stages, both in vitro and in vivo. Furthermore, decoquinate kills the parasite’s replicative blood stages and is active against developing gametocytes, the forms responsible for transmission. The drug acts by selectively and specifically inhibiting the parasite’s mitochondrial \(bc_1\) complex, with little cross-resistance with the antimalarial drug atovaquone. Oral administration of a single dose of decoquinate effectively prevents the appearance of disease, warranting its exploitation as a potent antimalarial compound.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3308910/pdf/Terms of Use
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