BIOCHEMICAL PHARMACOLOGY OF NEW ANTHRACYCLINES

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The overall goal for this research is to establish basic biochemical information on the mode of action of antitumor anthracyclines, on the structure-activity relationships for the biochemical events considered to be the cause(s) of toxicity and/or cytotoxicity (radical generation, lipid peroxidation, and DNA damage), and on the metabolic disposition and clearance of selected anthracyclines using perfused rat livers in vitro and the intact rat. We expect that this basic information will (1) contribute to the development and evaluation of concepts on the mode of action of the anthracyclines wherein initial bioactivation leads ultimately to antitumor action, (2) provide knowledge of the metabolism and disposition of selected compounds that exhibit high antitumor and/or lower toxicities in rodent test systems, and (3) stimulate the rational development of new antitumor anthracyclines.