Uncovering the Unusual Inhibition Mechanism of a Trypanosome Alternative Oxidase Inhibitor Displaying Broad-Spectrum Activity against African Animal Trypanosomes.

ABSTRACT: The glucose-dependent respiration of bloodstream forms of the parasite Trypanosoma brucei depends on an unusual and essential mitochondrial electron-transport system, consisting of glycerol-3-phosphate dehydrogenase and the trypanosome alternative oxidase (TAO). We report here the discovery of an allosteric inhibitor of TAO that displays highly potent activity (EC₅₀ values in the range 1-20 nM) against the important veterinary pathogens T. b. brucei, Trypanosoma evansi, Trypanosoma equiperdum, and Trypanosoma congolense, i.e., >5-fold greater potency than the standard drugs. The methylene-linked 2-methyl-4-hydroxybenzoate 2-pyridinyldiphenylphosphonium derivative (1) was the best inhibitor of recombinant TAO (IC₅₀ = 1.3 nM) vi

SUBMITTER: Ebiloma GU 

PROVIDER: S-EPMC12406258 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature