Targeting the Ubiquinol-Reduction (Q_i) Site of the Mitochondrial Cytochrome <i>bc₁</i> Complex for the Development of Next Generation Quinolone Antimalarials.

ABSTRACT: Antimalarials targeting the ubiquinol-oxidation (Q_o) site of the Plasmodium falciparum bc₁ complex, such as atovaquone, have become less effective due to the rapid emergence of resistance linked to point mutations in the Q_o site. Recent findings showed a series of 2-aryl quinolones mediate inhibitions of this complex by binding to the ubiquinone-reduction (Qi) site, which offers a potential advantage in circumventing drug resistance. Since it is essential to understand how 2-aryl quinolone lead compounds bind within the Qi site, here we describe the co-crystallization and structure elucidation of the bovine cytochrome bc₁ complex with three different antimalarial 4(1H)-quinolone sub-types, including two 2-aryl quinolone derivatives

SUBMITTER: Amporndanai K 

PROVIDER: S-EPMC9330653 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature