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

da Cruz, F. P. et al. (2012) Drug screen targeted at plasmodium liver stages identifies a potent multistage antimalarial drug. Journal of Infectious Diseases, 205(8), pp. 1278-1286. (doi: 10.1093/infdis/jis184) (PMID:22396598) (PMCID:PMC3308910)

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 bc1 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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Marti, Professor Matthias
• Authors: da Cruz, F. P., Martin, C., Buchholz, K., Lafuente-Monasterio, M. J., Rodrigues, T., Sonnichsen, B., Moreira, R., Gamo, F.-J., Marti, M., Mota, M. M., Hannus, M., and Prudencio, M.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Journal of Infectious Diseases
• Publisher: Oxford University Press
• ISSN: 0022-1899
• ISSN (Online): 1537-6613
• Published Online: 06 March 2012
• Copyright Holders: Copyright © 2012 The Authors
• First Published: First published in Journal of Infectious Diseases 205(8):1278-1286
• Publisher Policy: Reproduced under a Creative Commons License