Structural requirements of alkyl acyldithiocarbazates for the uncoupling of oxidative phosphorylation in mitochondria.
A structure-activity relationship study on the uncoupling of alkyl acyldithiocarbazates was carried out. Greater activity was observed with increasing alkyl chain length, the optimum being C9. A further increase in alkyl chain length caused a decrease in the activity. Thione-thiol tautomeric forms with a dissociable proton were dound to be of primary importance for the uncoupling and the role of the acyl group was auxiliary. The reactivity of the SH group of alkyl acyldithiocarbazates with an SH-reagent was very low. These compounds facilitated the valinomycin-induced swelling of non-respiring mitochondria and non-sonicated lecithin liposomes in isotonic potassium acetate solution.
D000818:Animals; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / Q000494:pharmacology; D004140:Dinitrophenols / Q000494:pharmacology; D006834:Hydrazines / Q000494:pharmacology; D007700:Kinetics; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism*; D008933:Mitochondrial Swelling / Q000187:drug effects; D010085:Oxidative Phosphorylation / Q000187:drug effects*; D051381:Rats; D013056:Spectrophotometry, Ultraviolet; D013329:Structure-Activity Relationship; D013438:Sulfhydryl Compounds / Q000494:pharmacology*; D014475:Uncoupling Agents / Q000494:pharmacology*
D004140:Dinitrophenols; D006834:Hydrazines; D013438:Sulfhydryl Compounds; D014475:Uncoupling Agents; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone