Targeted Structure-Activity Analysis of Endochin-like Quinolones Reveals Potent Qi and Qo Site Inhibitors of Toxoplasma gondii and Plasmodium falciparum Cytochrome bc₁ and Identifies ELQ-400 as a Remarkably Effective Compound against Acute Experimental Toxoplasmosis.

ABSTRACT: Cytochrome bc₁ inhibitors have been broadly studied as human and veterinary medicines and agricultural fungicides. For the most part, cytochrome bc₁ inhibitors compete with ubiquinol at the ubiquinol oxidation (Qo) site or with ubiquinone at the quinone reduction (Qi) site. 4(1 H)-Quinolones with 3-position substituents may inhibit either site based on quinolone ring substituents. 4(1 H)-Quinolones that inhibit the Qi site are highly effective against toxoplasmosis, malaria, and babesiosis and do not inhibit human cytochrome bc₁. We tested a series of 4(1 H)-Quinolones against wild-type and drug resistant strains of Toxoplasma gondii and Plasmodium falciparum. These experiments identified very potent compounds that inhibit T. gondii proliferation at picomol

SUBMITTER: McConnell EV 

PROVIDER: S-EPMC6884402 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature