NDLI: Atorvastatin Is a Promising Partner for Antimalarial Drugs in Treatment of Plasmodium falciparum Malaria▿

Content Provider	PubMed Central
Author	Parquet, Véronique Sébastien, Briolant Torrentino-madamet, Marylin Henry, Maud Almeras, Lionel Rémy, Amalvict Baret, Eric Thierry, Fusaï Rogier, Christophe Pradines, Bruno
Abstract	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.
Related Links	http://dx.doi.org/10.1128/aac.01462-08
Ending Page	2252
Page Count	5
Starting Page	2248
File Format	PDF
ISSN	00664804
e-ISSN	10986596
Journal	Antimicrobial Agents and Chemotherapy
Issue Number	6
Volume Number	53
Language	English
Publisher	American Society for Microbiology (ASM)
Publisher Date	2009-06-01
Access Restriction	Open
Rights Holder	American Society for Microbiology (ASM)
Subject Keyword	Pharmacology (medical) Pharmacology Infectious Diseases Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Infectious Diseases Pharmacology Pharmacology (medical)

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4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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