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Drug screen targeted at Plasmodium liver stages identifies a potent multistage antimalarial drug.


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.

SUBMITTER: da Cruz FP 

PROVIDER: S-EPMC3308910 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature

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Drug screen targeted at Plasmodium liver stages identifies a potent multistage antimalarial drug.

da Cruz Filipa P FP   Martin Cécilie C   Buchholz Kathrin K   Lafuente-Monasterio Maria J MJ   Rodrigues Tiago T   Sönnichsen Birte B   Moreira Rui R   Gamo Francisco-Javier FJ   Marti Matthias M   Mota Maria M MM   Hannus Michael M   Prudêncio Miguel M  

The Journal of infectious diseases 20120306 8


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  ...[more]

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