Artemisone and Artemiside Control Acute and Reactivated Toxoplasmosis in a Murine Model
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作者:
Dunay, Ildiko R.
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Washington Univ, Dept Mol Microbiol, Sch Med, St Louis, MO 63110 USAWashington Univ, Dept Mol Microbiol, Sch Med, St Louis, MO 63110 USA
Dunay, Ildiko R.
[1
]
Chan, Wing Chi
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Hong Kong Univ Sci & Technol, Open Lab Chem Biol, Inst Mol Technol Drug Discovery & Synth, Dept Chem, Kowloon, Hong Kong, Peoples R ChinaWashington Univ, Dept Mol Microbiol, Sch Med, St Louis, MO 63110 USA
Chan, Wing Chi
[2
]
Haynes, Richard K.
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Hong Kong Univ Sci & Technol, Open Lab Chem Biol, Inst Mol Technol Drug Discovery & Synth, Dept Chem, Kowloon, Hong Kong, Peoples R ChinaWashington Univ, Dept Mol Microbiol, Sch Med, St Louis, MO 63110 USA
Haynes, Richard K.
[2
]
Sibley, L. David
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Washington Univ, Dept Mol Microbiol, Sch Med, St Louis, MO 63110 USAWashington Univ, Dept Mol Microbiol, Sch Med, St Louis, MO 63110 USA
Sibley, L. David
[1
]
机构:
[1] Washington Univ, Dept Mol Microbiol, Sch Med, St Louis, MO 63110 USA
[2] Hong Kong Univ Sci & Technol, Open Lab Chem Biol, Inst Mol Technol Drug Discovery & Synth, Dept Chem, Kowloon, Hong Kong, Peoples R China
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.