Trypanocidal CoQ analogues: their effect on other mitochondrial systems.

1. A comparative study of compounds which inhibit the respiration of the infective form of the protozoan parasite Trypanosoma brucei brucei, such as salicylhydroxamic acid, other substituted benzhydroxamic acid, esters of 2,3- and 3,4-dihydroxybenzoic acid and structurally related compounds, showed that they have a remarkable degree of selectivity for the trypanosome as compared to rat liver mitochondria even though they are putative CoQ analogues and both respiratory systems are dependent on CoQ. 2. The minimal inhibition of mammalian mitochondrial function could not be assigned to inhibition of ubiquinone function in these mitochondria. 3. CoQ-reducing mitochondrial dehydrogenases from rat liver, trypanosomes and skunk cabbage (Symplocarpus foetidus) were insensitive to these inhibitors. 4. The alternative oxidase of skunk cabbage mitochondria was sensitive to a spectrum of trypanosome respiration inhibitors suggesting a similarity to the oxidase of the trypanosome although differing degrees of sensitivity and differing responses to alterations in the molecular structure of the inhibitors indicate that the milieu of the active sites are dissimilar.