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Antimicrobial Agents and Chemotherapy, October 2009, p. 4450-4456, Vol. 53, No. 10
0066-4804/09/$08.00+0     doi:10.1128/AAC.00502-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Artemisone and Artemiside Control Acute and Reactivated Toxoplasmosis in a Murine Model{triangledown}

Ildiko R. Dunay,1,§ Wing Chi Chan,2 Richard K. Haynes,2 and L. David Sibley1*

Department of Molecular Microbiology, Washington University School of Medicine, 660 S. Euclid Ave., St. Louis, Missouri 63110,1 Department of Chemistry, Open Laboratory of Chemical Biology, Institute of Molecular Technology for Drug Discovery and Synthesis, the Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong SAR, People's Republic of China2

Received 16 April 2009/ Returned for modification 27 May 2009/ Accepted 6 July 2009

Immunocompromised patients are at risk of developing toxoplasmosis, and although chemotherapy is available, standard treatments are often complicated by severe side effects. Artemisinin is a new highly potent antimalarial drug that has activity against Toxoplasma gondii in vitro. However, artemisinin derivatives have previously been ineffective in vivo using a rat model of toxoplasmosis. In the present study, the efficacy of several new artemisinin derivates was investigated for treatment of mice infected with the parasite Toxoplasma gondii. Artemiside and artemisone displayed better inhibition than either artemisinin or artesunate against the parasite in vitro. Artemiside and artemisone treatment controlled parasite replication in vivo, and mice survived the acute infection. In a murine model of reactivated toxoplasmosis, both drugs increased survival, although artemiside was more effective. These results indicate that these newer derivatives of artemisinin may have potential for treatment of toxoplasmosis.

* Corresponding author. Mailing address: Department of Molecular Microbiology, Washington University School of Medicine, 660 S. Euclid Ave., St. Louis, MO 63110. Phone: (314) 362-8873. Fax: (314) 286-0060. E-mail: sibley{at}borcim.wustl.edu

{triangledown} Published ahead of print on 27 July 2009.

§ Present address: Department of Neuropathology, University of Freiburg, Breihacher Str. 64, Freiburg D-79106, Germany.

Antimicrobial Agents and Chemotherapy, October 2009, p. 4450-4456, Vol. 53, No. 10
0066-4804/09/$08.00+0     doi:10.1128/AAC.00502-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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