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

Authors: 
Zhou Y, Fomovska A, Muench S, Lai BS, Mui E, McLeod R
Citation: 
Antimicrob Agents Chemother. 2014;58(3):1789-92. doi: 10.1128/AAC.02225-13. Epub 2013 Dec 23. PMID: 24366743
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.
Epub: 
Not Epub
Organism or Cell Type: 
Toxoplasma gondii
Delivery Method: 
peptide-linked