AffiliationCRC Department of Biophysical Chemistry, Paterson Institute for Cancer Research, Christie Hospital, Manchester, UK.
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AbstractThe 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.
CitationThe autoxidation of the reduced forms of EO9. 1996, 25 (2):141-8 Free Radic. Res.
JournalFree Radical Research
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- Authors: Everett SA, Naylor MA, Nolan J, Patel KB, Wardman P
- Issue date: 1998 Sep
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- Authors: Plumb JA, Gerritsen M, Workman P
- Issue date: 1994 Dec
- Involvement of NADPH: cytochrome P450 reductase in the activation of indoloquinone EO9 to free radical and DNA damaging species.
- Authors: Bailey SM, Lewis AD, Patterson LH, Fisher GR, Knox RJ, Workman P
- Issue date: 2001 Aug 15
- 5-substituted analogues of 3-hydroxymethyl-5-aziridinyl-1-methyl-2-[1H-indole-4,7-dione]prop-2-en- 1-ol (EO9, NSC 382459) and their regioisomers as hypoxia-selective agents: structure-cytotoxicity in vitro.
- Authors: Jaffar M, Naylor MA, Robertson N, Lockyer SD, Phillips RM, Everett SA, Adams GE, Stratford IJ
- Issue date: 1998 Mar
- Relative importance of DT-diaphorase and hypoxia in the bioactivation of EO9 by human lung tumor cell lines.
- Authors: Plumb JA, Gerritsen M, Milroy R, Thomson P, Workman P
- Issue date: 1994 May 15