Uncoupling effect of fungal hydroxyanthraquinones on mitochondrial oxidative phosphorylation.
Structure-uncoupling activity relationship of seven anthraquinone derivatives were investigated using rat liver mitochondria. Three compounds bearing the free hydroxyl group at the beta-position of their anthraquinone nucleus (1,3,6,8-tetrahydroxyanthraquinone, 1-acetyl-2,4,5,7-tetrahydroxy-9,10-anthracenedione and skyrin) exhibited uncoupling effect. Rugulosin, rugulin and physcion (all lacking the hydroxyl at the beta-position) were ineffective. Erythroglaucin, a derivative of physcion with the free hydroxyl group at the gamma-position, exhibited the highest uncoupling activity in the series tested. In addition, erythroglaucin abolished the energy dependent Ca2+ retention in mitochondria and induced Ca2+ leak. It also prevented the energization of mitochondrial membrane by ATP and induced a loss of the ATP induced membrane potential similarly as did carbonylcyanamide-3-chlorophenyl hydrazone (CCCP). The data show that the free hydroxyl group at either the gamma-position or the beta-position of anthraquinone nucleus is a prerequisite of the uncoupling activity of hydroxyanthraquinones.
D000818:Animals; D000880:Anthraquinones / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D008930:Mitochondria, Liver / Q000187:drug effects*; D010085:Oxidative Phosphorylation / Q000187:drug effects*; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D013329:Structure-Activity Relationship; D014475:Uncoupling Agents
D000880:Anthraquinones; D014475:Uncoupling Agents; D002118:Calcium