Spiroindolone That Inhibits PfATPase4 Is a Potent,Cidal Inhibitor of Toxoplasma gondii Tachyzoites In Vitro and In Vivo |
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Authors: | Ying Zhou Alina Fomovska Stephen Muench Bo-Shiun Lai Ernest Mui Rima McLeod |
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Affiliation: | aThe University of Chicago, Chicago, Illinois, USA ;bSchool of Biomedical Sciences, University of Leeds, Leeds, United Kingdom |
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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. |
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