Enzymatic oxidative activation of 5-iminodaunorubicin. Spectrophotometric and electron paramagnetic resonance studies

Horseradish peroxidase catalyzed oxidation of the antitumor agent 5-iminodaunorubicin by hydrogen peroxide was studied with both spectrophotometric and electron paramagnetic resonance methods. Kinetics of oxidation of the drug at pH 3, 6 and 8 were determined. Rapid formation of a nitrogen-centered free radical metabolite was demonstrated with electron paramagnetic resonance employing the 15N-labeled drug and by deuterium exchange techniques. This enzymatic oxidative activation of 5-iminodaunorubicin suggests an alternative mode of metabolism and mechanism of action of this less cardiotoxic anticancer agent. By contrast, the parent compound, daunorubicin, did not undergo oxidation by the horseradish peroxidase-hydrogen peroxide system.