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Experimental Therapeutics

Spiroindolone That Inhibits PfATPase4 Is a Potent, Cidal Inhibitor of Toxoplasma gondii Tachyzoites In Vitro and In Vivo

Ying Zhou, Alina Fomovska, Stephen Muench, Bo-Shiun Lai, Ernest Mui, Rima McLeod
Ying Zhou
aThe University of Chicago, Chicago, Illinois, USA
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Alina Fomovska
aThe University of Chicago, Chicago, Illinois, USA
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Stephen Muench
bSchool of Biomedical Sciences, University of Leeds, Leeds, United Kingdom
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Bo-Shiun Lai
aThe University of Chicago, Chicago, Illinois, USA
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Ernest Mui
aThe University of Chicago, Chicago, Illinois, USA
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Rima McLeod
aThe University of Chicago, Chicago, Illinois, USA
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DOI: 10.1128/AAC.02225-13
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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.

FOOTNOTES

    • Received 14 October 2013.
    • Returned for modification 7 November 2013.
    • Accepted 15 December 2013.
    • Accepted manuscript posted online 23 December 2013.
  • Supplemental material for this article may be found at http://dx.doi.org/10.1128/AAC.02225-13.

  • Copyright © 2014, American Society for Microbiology. All Rights Reserved.
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Spiroindolone That Inhibits PfATPase4 Is a Potent, Cidal Inhibitor of Toxoplasma gondii Tachyzoites In Vitro and In Vivo
Ying Zhou, Alina Fomovska, Stephen Muench, Bo-Shiun Lai, Ernest Mui, Rima McLeod
Antimicrobial Agents and Chemotherapy Feb 2014, 58 (3) 1789-1792; DOI: 10.1128/AAC.02225-13

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Spiroindolone That Inhibits PfATPase4 Is a Potent, Cidal Inhibitor of Toxoplasma gondii Tachyzoites In Vitro and In Vivo
Ying Zhou, Alina Fomovska, Stephen Muench, Bo-Shiun Lai, Ernest Mui, Rima McLeod
Antimicrobial Agents and Chemotherapy Feb 2014, 58 (3) 1789-1792; DOI: 10.1128/AAC.02225-13
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