Acridones Are Highly Potent Inhibitors of <i>Toxoplasma gondii</i> Tachyzoites
P. Holland Alday, Erin V. McConnell, Jan M. Boitz Zarella, Rozalia A. Dodean, Papireddy Kancharla, Jane X. Kelly, J. Stone Doggett
Abstract
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 bc1 and dihydroorotate dehydrogenase and identify acridones that bind preferentially to the Qi site of cytochrome bc1. 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.
Topics & Concepts
AcridoneToxoplasma gondiiIn vitroIn vivoBiologyDihydroorotate dehydrogenaseToxoplasmosisProtozoaEnzymeBiochemistryChemistryVirologyMicrobiologyImmunologyAntibodyStereochemistryGeneticsToxoplasma gondii Research StudiesParasitic Infections and DiagnosticsHerpesvirus Infections and Treatments