BIOTRANSFORMATIONS OF DAUNORUBICIN AGLYCONES BY RAT-LIVER MICROSOMES

  • 1 January 1984
    • journal article
    • research article
    • Vol. 44  (6) , 2480-2484
Abstract
Daunorubicin [antitumor drug] is biotransformed anaerobically by rat liver microsomes with a NADPH-generating system to form a series of aglycones. The 1st reaction, reductive cleavage of daunosamine (at C-7 in ring A) to form the 7-deoxyaglycone, is followed by reduction of the C-13 keto group. The 7-hydroxyaglycone may also form by hydrolytic cleavage of the amino sugar followed then by the same C-13 keto reduction. These reactions are not inhibited by .beta.-diethylaminoethyldiphenylpropyl acetate, whereas subsequent reactions in the D ring of the aglycones can be completely blocked by this cytochrome P-450 inhibitor: reductive and hydrolytic cleavage of the C-4 methoxy group. Thus, 5 reactions at 3 sites are described and theoretical pathways are proposed for the expected 12 aglycones from daunorubicin.