Free Radical Formation by Cytotoxic Alkylaminoanthraquinones in Liver Microsomes
The anthracycline antibiotics as exemplified by doxorubicin and daunorubicin are widely used antitumour agents. The mechanism of toxicity of these agents probably involves damage to multiple sites within cell systems since DNA binding, DNA strand breakage, enzyme inactivation, and membrane effects have all been described.1 The planar chromophore and cationic nature of the clinically important anthracyclines are essential to many of their interactions with biological systems especially intercalative binding to DNA2 and free radical generation.3 Mitozantrone is an alkylaminoanthraquinone antitumour agent which has been developed from a consideration of the modes of action of the anthracyclines and although a more simplified derivative it has a similar activity with respect to DNA binding4 and also generates free radicals.5 To explore further the structural factors influencing DNA binding and free radical generation by alkylaminoanthraquinones we have prepared derivatives based on the anthraquinone chromophore.6 In this study metabolic free radical generation by four alkylaminoanthraquinones (compounds 1–4) that differ in the substitution pattern is described (Figure 1).
KeywordsElectron Spin Resonance Electron Spin Resonance Spectrum Free Radical Generation Free Radical Formation NADPH Oxidation
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