Semiquinones derived from anthraquinone-containing antitumor drugs can partition into phosphatidylcholine bilayers

Semiquinones derived from anthraquinone-containing antitumor drugs (doxorubicin, daunorubicin and 4'-epidoxorubicin) were generated by the hypoxanthine/xanthine oxidase system in argon-saturated phosphate buffer (pH 7.4) in the presence of egg-yolk phosphatidylcholine multilamellar vesicles (MLVs) containing 1 mol% of a doxylstearic acid (DSA) isomer. The destruction of the electron spin resonance signal corresponding to 5-, 12- and 15-DSA included in the MLVs follows pseudo-first-order kinetics. Higher rates of destruction are obtained for the 12-DSA isomer which indicates that these semiquinones can localize preferentially about the depth of the 12th position of stearic acid in membranes. It is demonstrated that DSA destruction is due to a reversible reduction of DSA to the hydroxylamine species. This work shows that anthracycline semiquinones can partition into phosphatidylcholine bilayers under anoxic conditions which may imply another pathway in their cytotoxic action.