Abstract
In order to study the metabolism of daunomycin, methods were developed for the purification of daunomycin (D1) by silicic acid column chromatography and for the isolation of fluorescent metabolites on silica gel thin-layer chromatography. Two predominant fluorescent metabolites, D2 and D3, were observed when rat tissue slices were incubated with D1. The characteristics of D2 were unlike any previously reported metabolite of daunomycin. Whereas D2 was formed by all the tissues tested, D3 was not. Hydrolysis of D2 under mild conditions yielded D3, a proposed aglycone. Since the ultraviolet-visible absorption and the fluorescence spectra of D1, D2, D3, and daunomycinone (D4) were very similar, whereas the chromatographic characteristics were different, it was proposed that the metabolic conversion of D1 to D2, involved an alteration of the saturated ring or side chains of the tetracycline moiety of D1. In addition, the kinetics of D2, formation by rat kidney slices and the apparent dependence of D3 formation on the presence of D2 support a proposed metabolic sequence of D1 → D2 → D3. Evidence for other nonfluorescent metabolites was seen when radioactive D1 was incubated with tissue slices.
Footnotes
- Received November 7, 1969.
- Accepted July 14, 1970.
- © 1970 by The Williams & Wilkins Co.
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