Autoxidation of the antitumor drug 9-hydroxyellipticine and its derivatives.
In aqueous solution and using molecular oxygen as electron acceptor, the antitumor drug 9-hydroxyellipticine (9-OH-E) undergoes a spontaneous oxidation to give hydrogen peroxide (H2O2), the quinone imine 9-oxoellipticine (9-oxo-E), and a dimer of 9-OH-E(9-OH-E2). Electron paramagnetic resonance (EPR) experiments performed either in alkaline Me2SO or in phosphate buffer in the presence of the spin trap 5,5-dimethylpyrroline 1-oxide (DMPO) suggest that the oxidation process involves the initial formation of superoxide anion (O2- .) and the free radical of the drug. In aqueous medium, this step is followed by the dismutation of both O2- . and free radicals of the drug generating, respectively, H2O2 and 9-oxo-E. 9-Oxo-E further reacts with the 9-OH-E remaining in the solution to form the dimer 9-OH-E2 as the terminal product. The autoxidation process is strongly enhanced by superoxide dismutase and manganese ions. In the ellipticine series, all drugs that have an OH group in position 9 exhibit the ability to transfer one electron on molecular oxygen to generate O2- .. This property may be involved in the cytotoxic activities of these drugs.
D000470:Alkaloids; D055598:Chemical Phenomena; D002621:Chemistry; D004492:Edetic Acid; D004611:Ellipticines; D007700:Kinetics; D008345:Manganese; D010084:Oxidation-Reduction; D010101:Oxygen Consumption; D013053:Spectrophotometry; D013329:Structure-Activity Relationship; D013482:Superoxide Dismutase / Q000378:metabolism
D000470:Alkaloids; D004611:Ellipticines; D008345:Manganese; D004492:Edetic Acid; C008009:9-hydroxyellipticine; D013482:Superoxide Dismutase