Superoxide radical reactions with anthracycline antibiotics

The reaction of superoxide with daunorubicin or its aglycones in the aprotic solvents dimethyl sulfoxide and dimethylformamide was studied. This interaction generated the blue anthracycline phenolate anion as monitored by u.v.-visible spectrometry and molecular oxygen as determined by a modified Clark-type oxygen electrode. The visible spectrum of the phenolate anion (gamma max 604, 652 nm) was subject to considerable shifts dependent on the size of the cation present. The phenolate anion could be further oxidized by molecular oxygen to generate the C-6, C-11 (B-ring) semiquinone as detected by a weak electron paramagnetic resonance spectrometry signal. These results raise the possibility that similar reactions of superoxide with anthracyclines in vivo may play a role in the antitumor activity and/or the etiology of the toxic side effects of this class of drugs.