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Antimicrobial Agents and Chemotherapy, June 2009, p. 2248-2252, Vol. 53, No. 6
0066-4804/09/$08.00+0     doi:10.1128/AAC.01462-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Atorvastatin Is a Promising Partner for Antimalarial Drugs in Treatment of Plasmodium falciparum Malaria{triangledown}

Véronique Parquet,1 Sébastien Briolant,1 Marylin Torrentino-Madamet,2 Maud Henry,1 Lionel Almeras,1 Rémy Amalvict,1 Eric Baret,1 Thierry Fusaï,1 Christophe Rogier,1 and Bruno Pradines1*

Unité de Recherche en Biologie et Epidémiologie Parasitaires, Unité de Recherche pour les Maladies Infectieuses et Tropicales Emergentes, UMR 6236, Institut de Recherche Biomédicale des Armées, Institut de Médecine Tropicale du Service de Santé des Armées, Marseille, France,1 Unité de Recherche en Physiologie et Pharmacocinétique Parasitaires, UMR-MD3 Relations Hôte-Parasites, Pharmacologie et Thérapeutique, Institut de Médecine Tropicale du Service de Santé des Armées, Marseille, France2

Received 2 November 2008/ Returned for modification 24 January 2009/ Accepted 14 March 2009

Atorvastatin (AVA) is a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor. AVA exposure resulted in the reduced in vitro growth of 22 Plasmodium falciparum strains, with the 50% inhibitory concentrations (IC50s) ranging from 2.5 µM to 10.8 µM. A significant positive correlation was found between the strains’ responses to AVA and mefloquine (r = 0.553; P = 0.008). We found no correlation between the responses to AVA and to chloroquine, quinine, monodesethylamodiaquine, lumefantrine, dihydroartemisinin, atovaquone, or doxycycline. These data could suggest that the mechanism of AVA uptake and/or the mode of action of AVA is different from those for other antimalarial drugs. The IC50s for AVA were unrelated to the occurrence of mutations in the transport protein genes involved in quinoline antimalarial drug resistance, such as the P. falciparum crt, mdr1, mrp, and nhe-1 genes. Therefore, AVA can be ruled out as a substrate for the transport proteins (CRT, Pgh1, and MRP) and is not subject to the pH modification induced by the P. falciparum NHE-1 protein. The absence of in vitro cross-resistance between AVA and chloroquine, quinine, mefloquine, monodesethylamodiaquine, lumefantrine, dihydroartemisinin, atovaquone, and doxycycline argues that these antimalarial drugs could potentially be paired with AVA as a treatment for malaria. In conclusion, the present observations suggest that AVA is a good candidate for further studies on the use of statins in association with drugs known to have activities against the malaria parasite.

* Corresponding author. Mailing address: Unité de Recherche en Biologie et Épidémiologie Parasitaires, Institut de Recherche Biomédicale des Armées, Institut de Médecine Tropicale du Service de Santé des Armées, Allée du Médecin-Colonel Jamot, Parc le Pharo, BP 60109, Marseille 13262 Cedex 07, France. Phone: 33 4 91 15 01 10. Fax: 33 4 91 15 01 64. E-mail: bruno.pradines{at}free.fr

{triangledown} Published ahead of print on 13 March 2009.

Antimicrobial Agents and Chemotherapy, June 2009, p. 2248-2252, Vol. 53, No. 6
0066-4804/09/$08.00+0     doi:10.1128/AAC.01462-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Savini, H., Souraud, J. B., Briolant, S., Baret, E., Amalvict, R., Rogier, C., Pradines, B. (2010). Atorvastatin as a Potential Antimalarial Drug: In Vitro Synergy in Combinational Therapy with Dihydroartemisinin. Antimicrob. Agents Chemother. 54: 966-967 [Full Text]  


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