PMID: 1908911Mar 1, 1991

Structure-sensitivity relationship of anthracycline antibiotics to C7-reduction by redox enzymes

The Japanese journal of antibiotics
A YoshimotoT Takeuchi

Abstract

About 30 antitumor anthracycline antibiotics were tested for their susceptibilities to reductive deglycosidation at C-7 catalyzed by rat liver microsomal NADPH-cytochrome P-450 reductase, xanthine oxidase, cytochrome C reductase and DT-diaphorase. Enzymatic activities to reduce the C-7 position of anthracycline antibiotics were similar among the four redox enzymes although a few exceptions were observed with DT-diaphorase. Among therapeutic use of anthracyclines, aclacinomycin A (ACM-A, aclarubicin) and daunomycin (daunorubicin) were found to be highly sensitive to the redox enzymes tested while adriamycin (ADM, doxorubicin) and THP-ADM (pirarubicin) were resistant to enzymatic reductive deglycosidation. When glycosidic and hydroxylated analogs of ACM-A were compared it was found that anthracyclines with smaller glycoside residues were more sensitive to the redox enzymes and the presence of hydroxyl groups on the aglycone moiety decreased the reductive deglycosidation activities. Thus, the aglycone, aklavinone, was most rapidly reduced to 7-deoxyaklavinone. 1-Hydroxy-, 2-hydroxy-, 11-hydroxy- and 1,11-dihydroaclacinomycins A were more resistant to the redox enzymes that ACM-A. Especially, 2-hydroxyaclacinomycins were completely...Continue Reading

Related Concepts

Metazoa
Antibiotics, Cytotoxic
Microsomes, Liver
Cytochrome c Reductase
NADPH-Ferrihemoprotein Reductase
Oxidation-Reduction
Menaquinone Reductases
Xanthine Oxidase
Rats, Laboratory
Aclarubicin

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