Endochin-like quinolones are highly efficacious against acute and latent experimental toxoplasmosis

摘要: Toxoplasma gondii is a widely distributed protozoan pathogen that causes devastating ocular and central nervous system disease. We show the endochin-like quinolone (ELQ) class of compounds contains extremely potent inhibitors T. growth in vitro effective against acute latent toxoplasmosis mice. screened 50 ELQs selected two lead compounds, ELQ-271 ELQ-316, for evaluation. have IC50 values 0.1 nM 0.007 nM, respectively. ELQ-316 ED50 0.14 mg/kg 0.08 when administered orally to mice with toxoplasmosis. Moreover, are highly active cyst form at low doses, reducing burden by 76–88% after 16 d treatment. To investigate ELQ mechanism action gondii, we demonstrate endochin inhibit cytochrome c reduction bc1 complex 8 31 also inhibits Saccharomyces cerevisiae complex, an M221Q amino acid substitution Qi site protein leads >100-fold resistance. conclude bioavailable drugs toxoplasmosis, likely acting as complex.