Role of Oxygen and of Superoxide Radical in the Mechanisms of Monoelectronic Activation of Various Xenobiotics : A Radiolysis Study
Many xenobiotics need a free-radical mediated metabolism activation to exhibit their biological properties. Among them, antitumor drugs such as anthracycline or ellipticine derivatives are known to be enzymically activated by one-electron transfer. We present here two anticancer agents: an ellipticine substituted derivative, EH2 (scheme 1) which has a paraaminophenol structure and daunorubicin, DOS (scheme 2) which is an anthra-cycline antibiotic with a quinone group. Both these anticancer agents possess a resonant plane structure which allows their intercalation in DNA and each drug has a side group which enhances this intercalation ability (an amino side chain for EH2 and a sugar for DOS). During the metabolism of these antitumor agents, oxygen and/or reactive oxygen species are required forthe development of their cytotoxic properties. Hence we have investigated the interaction of 02 and/or 02 ∸ with the radical transient of each drug. In both cases pulse radiolysis combined with kinetic spectroscopy is well appropriated for such studies of model in vitro systems. Indeed this technique gives free radicals in homogeneous solution in a determined amount and allows the direct observation of the free radical reactions with substrates.
KeywordsSugar Recombinates Superoxide Cysteine Doxorubicin
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