Novel anthraquinone derivatives with redox-active functional groups capable of producing free radicals by metabolism: are free radicals essential forcytotoxicity?

The mode of action of antitumour anthraquinone derivatives (i.e. mitoxantro ne) is not clearly established yet. It includes, among others, intercalatio n and binding to DNA, bioreduction and aerobic redox cycling. A series of a nthraquinone derivatives, with potentially bioreducible groups sited in the side chain, have been synthesized and biologically evaluated. Their redox and cytotoxic activities were screened. Derivatives which bear a 2-(dimethy lamino)ethylamino substituent, known to confer high DNA affinity, demonstra ted cytotoxicity but not redox activity (beside the anthraquinone reduction ). Conversely, derivatives which showed redox activity were not cytotoxic t oward the P388 cell line. The results suggest that bioreduction is not the main mode of action in the cytotoxicity of anthraquinones. (C) 1999 Edition s scientifiques et medicales Elsevier SAS.