FREE-RADICAL INTERMEDIATES IN THE OXIDATION OF FLAVONE-8-ACETIC ACID - POSSIBLE INVOLVEMENT IN ITS ANTITUMOR-ACTIVITY

The sulphate radical (SO4.-), a model one-electron oxidant, reacts with the antitumour drug flavone-8-acetic acid (FAA) with the rate constant 9.1 x 10(8) dm3mol-1 s-1 to yield an uncharged radical that reacts with oxygen (k almost-equal-to 1 X 10(9) dm3mol-1 s-1). The oxidation of FAA by SO4.- in a steady-state system was found to release carbon dioxide with a yield of 96% relative to that of the SO4.-. The results are interpreted by fast (t1/2 less-than-or-equal-to 1 mus) and efficient decarboxylation of the FAA radical cation, resulting in a carbon-centred radical. The reaction of the latter with oxygen is a possible source of radical-driven cytotoxic pathways, such as singlet oxygen formation via the Russell mechanism or H-abstraction from lipids. On the basis of the observations in the model system, a possible free radical mechanism for the antitumour action of the drug is suggested.