Abstract
Daunomycin, a glycosidic anthracycline, is metabolized in vitro to two newly identified aglycone metabolites, 8-(1-hydroxyethyl)-7,8,9,10-tetrahydro-6,8,11-trihydroxyl-1-methoxy-5, 12-naphthacenedione (Dz) and 8-acetyl-7,8,9,10-tetrahydro-6,8,11-trihydroxyl-1-methoxy-5, 12-naphthacenedione (Dy). Two similar aglycone metabolites of adriamycin have been identified as 8-(1,2-dihydroxyethyl)-7,8,9,10-tetrahydro-6,8,11-trihydroxy-1-methoxy-5, 12-naphthacenedione (Az), and 8-hydroxyacetyl-7,8,9,10-tetrahydro-6,8,11-trihydroxy-1-methoxy-5, 12-naphthacenedione (Ay). At least two distinct reactions are involved in the formation of these metabolites. One is a reductive glycosidic cleavage which occurs in the conversion of daunomycin to Dy and in the conversion of the glycosidic metabolite D2 to Dz. The other reaction is dependent upon the reduction of the acetyl group of daunomycin to hydroxy ethyl. This occurs in the conversions of daunomycin to D2 and of Dy to Dz. The adriamycin reactions are analogous to those of daunomycin. Daunomycin is metabolized by liver and kidney homogenates. In liver the metabolic pathway proceeds by conversion of daunomycin (D1) to Dy, which is then converted to Dx. In kidney, the sequence involves conversion of D1 to a glycosidic metabolite D2 which is then converted to Dx. Thus, the major difference between the liver and kidney pathways seems to be the order in which the two reactions occur. In the postulated pathway for adriamycin metabolism in hamster and rat liver, adriamycin is converted to Ay which is, in turn, converted to Ax.
Footnotes
- Received November 19, 1971.
- Accepted April 4, 1972.
- © 1972, by The Williams & Wilkins Company
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