The autoxidation of the reduced forms of EO9.
The properties of the semiquinone radical from [3-hydroxy-5-aziridinyl-1-methyl-2-(1H-indole-4,7-indi one)-prop-beta-en-alpha-ol], EO9, have been studied using pulse-radiolysis techniques. The reduction potential of the semiquinone of EO9 at pH7.4, E(EO9/EO9-), is -253 +/- 6 mV and hence this quinone can be readily reduced by one-electron reducing enzymes such as cytochrome P450 reductase and xanthine oxidase. However, the radical is unstable in the presence of oxygen (k = 1.3 +/- 0.15 x 10(8) M-1 s-1). The semiquinone radicals and the hydroquinone are in equilibrium although the formation of the hydroquinone is favoured t physiologically relevant pH. The hydroquinone of EO9 is also unstable in the presence of oxygen and it is predicted that in fully aerated solutions, its half life is 1.5 +/- 0.3 seconds. These results are discussed in view of the selective cytotoxicity of EO9 and its ability to undergo bioreductive activation by one-electron reducing enzymes and DT-diaphorase.
Butler
J
J
CRC Department of Biophysical Chemistry, Paterson Institute for Cancer Research, Christie Hospital, Manchester, UK.
Spanswick
V J
VJ
Cummings
J
J
D000970:Antineoplastic Agents / Q000737:chemistry*; D001388:Aziridines / Q000737:chemistry*; D004355:Drug Stability; D005609:Free Radicals; D006207:Half-Life; D006863:Hydrogen-Ion Concentration; D006873:Hydroquinones / Q000737:chemistry; D045563:Indolequinones; D007211:Indoles / Q000737:chemistry*; D010084:Oxidation-Reduction; D010100:Oxygen / Q000494:pharmacology; D011675:Pulse Radiolysis; D013053:Spectrophotometry
D000970:Antineoplastic Agents; D001388:Aziridines; D005609:Free Radicals; D006873:Hydroquinones; D045563:Indolequinones; D007211:Indoles; C060817:apaziquone; D010100:Oxygen; C031927:hydroquinone