Anthracycline antibiotic pharmacology and metabolism.
The anthracycline antibiotics show evidence of numerous interactions with cellular components and participation in several metabolic pathways. Small structural changes in the antibiotic molecule can produce major changes in intracellular localization and interaction. To date, we find that all of the anthracycline antibiotics form free radical intermediates through the catalysis of microsomal and nuclear electron-transport machinery. NADPH cytochrome P-450 reductase catalyzes the free radical formation. The free radical intermediates ("site-specific free radicals") may be causative of both toxicity and pharmaceutic action. The free radical intermediates degrade nonenzymatically to 7-deoxyaglycone metabolites which prove the existence of the free radical in vivo.
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000378:metabolism* / Q000494:pharmacology; D002360:Carubicin / Q000378:metabolism; D055598:Chemical Phenomena; D002621:Chemistry; D003630:Daunorubicin / Q000031:analogs & derivatives / Q000378:metabolism; D004317:Doxorubicin / Q000031:analogs & derivatives / Q000378:metabolism; D006027:Glycosides / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D009279:Naphthacenes / Q000378:metabolism* / Q000494:pharmacology
D000903:Antibiotics, Antineoplastic; D006027:Glycosides; D009279:Naphthacenes; D004317:Doxorubicin; D002360:Carubicin; D003630:Daunorubicin