Acridones Are Highly Potent Inhibitors of Toxoplasma gondii Tachyzoites

Acridone derivatives, which have been shown to have in vitro and in vivo activity against Plasmodium spp, inhibit Toxoplasma gondii proliferation at picomolar concentrations. Using enzymatic assays, we show that acridones inhibit both T. gondii cytochrome bc 1 and dihydroorotate dehydrogenase and identify acridones that bind preferentially to the Qi site of cytochrome bc 1. We identify acridones that have efficacy in a murine model of systemic toxoplasmosis. Acridones have potent activity against T. gondii and represent a promising new class of preclinical compounds.