Abstract
Here, we show that spiroindolone, an effective treatment for plasmodia, is also active against Toxoplasma gondii tachyzoites. In vitro, spiroindolone NITD609 is cidal for tachyzoites (50% inhibitory concentration [IC50], 1μM) and not toxic to human cells at ≥10μM. Two daily oral doses of 100 mg/kg of body weight reduced the parasite burden in mice by 90% (P=0.002), measured 3 days after the last dose. This inhibition of T. gondii tachyzoites in vitro and in vivo indicates that spiroindolone is a promising lead candidate for further medicine development.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenosine Triphosphatases / antagonists & inhibitors
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Animals
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Coccidiostats / pharmacology
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Coccidiostats / therapeutic use*
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Humans
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In Vitro Techniques
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Indoles / pharmacology
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Indoles / therapeutic use*
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Mice
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Microbial Sensitivity Tests
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Spiro Compounds / pharmacology
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Spiro Compounds / therapeutic use*
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Toxoplasma / drug effects*
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Toxoplasma / enzymology
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Toxoplasmosis / drug therapy*
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Toxoplasmosis, Animal / drug therapy
Substances
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Coccidiostats
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Indoles
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NITD 609
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Spiro Compounds
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Adenosine Triphosphatases