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Antimicrobial Agents and Chemotherapy, May 2006, p. 1731-1737, Vol. 50, No. 5
0066-4804/06/$08.00+0     doi:10.1128/AAC.50.5.1731-1737.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Antimalarial Activity of Allicin, a Biologically Active Compound from Garlic Cloves

Alida Coppi,1 Melissa Cabinian,1 David Mirelman,2 and Photini Sinnis1*

Department of Medical Parasitology, New York University School of Medicine, New York, New York 10010,1 Department of Biological Chemistry, Weizmann Institute of Science, Rehovot, Israel2

Received 21 October 2005/ Returned for modification 22 November 2005/ Accepted 1 March 2006

The incidence of malaria is increasing, and there is an urgent need to identify new drug targets for both prophylaxis and chemotherapy. Potential new drug targets include Plasmodium proteases that play critical roles in the parasite life cycle. We have previously shown that the major surface protein of Plasmodium sporozoites, the circumsporozoite protein (CSP), is proteolytically processed by a parasite-derived cysteine protease, and this processing event is temporally associated with sporozoite invasion of host cells. E-64, a cysteine protease inhibitor, inhibits CSP processing and prevents invasion of host cells in vitro and in vivo. Here we tested allicin, a cysteine protease inhibitor found in garlic extracts, for its ability to inhibit malaria infection. At low concentrations, allicin was not toxic to either sporozoites or mammalian cells. At these concentrations, allicin inhibited CSP processing and prevented sporozoite invasion of host cells in vitro. In vivo, mice injected with allicin had decreased Plasmodium infections compared to controls. When sporozoites were treated with allicin before injection into mice, malaria infection was completely prevented. We also tested allicin on erythrocytic stages and found that a 4-day regimen of allicin administered either orally or intravenously significantly decreased parasitemias and increased the survival of infected mice by 10 days. Together, these experiments demonstrate that the same cysteine protease inhibitor can target two different life cycle stages in the vertebrate host.


* Corresponding author. Mailing address: Department of Medical Parasitology, 341 East 25th Street, New York, NY 10010. Phone: (212) 263-6818. Fax: (212) 263-8116. E-mail: photini.sinnis{at}med.nyu.edu.


Antimicrobial Agents and Chemotherapy, May 2006, p. 1731-1737, Vol. 50, No. 5
0066-4804/06/$08.00+0     doi:10.1128/AAC.50.5.1731-1737.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.




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