title: Spiroindolone that inhibits PfATPase4 is a potent, cidal inhibitor of Toxoplasma gondii tachyzoites in vitro and in vivo.
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.
authors.affiliation: The University of Chicago, Chicago, Illinois, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhou
authors.forename: Alina
authors.initials: A
authors.lastname: Fomovska
authors.forename: Stephen
authors.initials: S
authors.lastname: Muench
authors.forename: Bo-Shiun
authors.initials: BS
authors.lastname: Lai
authors.forename: Ernest
authors.initials: E
authors.lastname: Mui
authors.forename: Rima
authors.initials: R
authors.lastname: McLeod
mesh_terms: D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors; D000818:Animals; D003049:Coccidiostats / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology / Q000627:therapeutic use*; D051379:Mice; D008826:Microbial Sensitivity Tests; D013141:Spiro Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D014122:Toxoplasma / Q000187:drug effects* / Q000201:enzymology; D014123:Toxoplasmosis / Q000188:drug therapy*; D014124:Toxoplasmosis, Animal / Q000188:drug therapy
chemical_list: D003049:Coccidiostats; D007211:Indoles; C552304:NITD 609; D013141:Spiro Compounds; D000251:Adenosine Triphosphatases