Bioenergetics in clinical medicine: prevention by forms of coenzyme Q of the inhibition by adriamycin of coenzyme Q10-enzymes in mitochondria of the myocardium.
Adriamycin inhibits the succinoxidase system and the NADH-oxidase system. Both of the intact mitocondrial enzymes and the pentane-extracted preparations are inhibited. The inhibition can be prevented by a molar ratio of coenzyme to adriamycin of 3:1 for coenzyme Q10 (ubiquinone), 5:1 for coenzyme Q7, and 5:1 for coenzyme Q4. Prevention of inhibition was observed in the decreasing order of coenzyme Q10 greater than coenzyme Q7 greater than H6 coenzyme Q4 greater than coenzyme Q4. Adriamycinone was three times more inhibitory than adriamycin, which is compatible with a less polar fragment necessary to inhibit the lipoidal coenzyme Q10. Daunomycinone was not inhibitory at a concentration at which adriamycinone is effective, indicating that the hydroxyl group of the latter could be binding at the receptor, since it should not influence electron transfer or rings B and C.
D000818:Animals; D002417:Cattle; D003630:Daunorubicin / Q000031:analogs & derivatives / Q000494:pharmacology; D004317:Doxorubicin / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors*; D011808:Quinone Reductases / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D013385:Succinate Dehydrogenase / Q000037:antagonists & inhibitors*; D014451:Ubiquinone / Q000494:pharmacology*
D014451:Ubiquinone; D004317:Doxorubicin; D013385:Succinate Dehydrogenase; D009247:NADH, NADPH Oxidoreductases; D011808:Quinone Reductases; D003630:Daunorubicin