Novel anthraquinone derivatives with redox-active functional groups capable of producing free radicals by metabolism: are free radicals essential forcytotoxicity?
D. Barasch et al., Novel anthraquinone derivatives with redox-active functional groups capable of producing free radicals by metabolism: are free radicals essential forcytotoxicity?, EUR J MED C, 34(7-8), 1999, pp. 597-615
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.