Syntheses and uncoupling activities of alkyl dithiocarbazates and alkyl pyridinecarbonyldithiocarbazates.
A series of alkyl dithiocarbazates, alkyl 3-picolinoyldithiocarbazates, alkyl 3-nicotinoyldithiocarbazates, alkyl 3-isonicotinoyldithiocarbazates, and alkyl 3-picolinoyl-2-methyldithiocarbazates was prepared. These alkyl pyridinecarbonyldithiocarbazates were shown to be uncouplers of oxidative phosphorylation in mitochondria. The finding that uncoupling activity increased with increase in the length of the alkyl chains of the compounds indicates that hydrophobicity influences the activity. The nonyl derivatives had the highest activity. The results also suggested that a dissociable acidic proton is necessary for the uncoupling activity.
D000818:Animals; D005971:Glutamates / Q000378:metabolism; D066298:In Vitro Techniques; D008293:Malates / Q000378:metabolism; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism; D010085:Oxidative Phosphorylation / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D013329:Structure-Activity Relationship; D013386:Succinates / Q000378:metabolism; D013859:Thiocarbamates / Q000138:chemical synthesis* / Q000494:pharmacology; D014475:Uncoupling Agents / Q000138:chemical synthesis*
D005971:Glutamates; D008293:Malates; D013386:Succinates; D013859:Thiocarbamates; D014475:Uncoupling Agents