Electron Spin Resonance of The Semiquinone of The Antitumor Antibiotic Streptonigrin and Its Metal Complexes
Mechanistic elucidation of the redox chemistry of aminoquinone antibiotics exhibiting potent antitumor activity has become one of the most timely problems of cancer chemotherapy today1,2. Specifically, streptronigrin (Figure 1a), is currently regarded as one of the most effective agents for the treatment of a broad spectrum of human cancers3, yet its clinical application is greatly limited due to severe cytotoxicity of the drug. It has been reported that streptonigrin is activated in vivo by one-electron reduction forming the semiquinone4–6 and that the mechanism of antitumor action of streptonigrin depends on participation of metal ions7.
KeywordsElectron Spin Resonance Electron Spin Resonance Spectrum Cadmium Acetate Potent Antitumor Activity Phenazine Methosulfate
Unable to display preview. Download preview PDF.
- 4.J. R. White, H. H. Dearman, Generation of Free Radicals From Phenazine Methosulfate, Streptonigrin, and Riboflavin in Bacterial Suspensions, Proc. Natl. Acad. Sci. (USA) 59:887(1965).Google Scholar
- 5.K. Ishizu, H. H. Dearman, M. T. Huang, J. R. White, Electron Paramagnetic Resonance Observations in Biogenic Semiquinone and 5-methyl Phenazinium Radicals, Biochim. Biophys. Acta 165:283(1968).Google Scholar
- 8.H. L. White, J. R. White, Lethal Action and Metabolic Effects of Streptonigrin in Escherichia coli, Mol. Pharmacol. 4:549(1968).Google Scholar
- 9.It should be pointed out that these reports merely presented the recorded ESR spectra as experimental evidence for the formation of radicals, providing no assignments or correlation between the obtained spectra and the putative semiquinone structure (cf. ref. 4–6).Google Scholar
- 12.J. D. R. Clay, D. J. Murphy, Electron Spin Resonance Spectra of Aminosemiquinones and Diaminosemiquinones, J. Chem. Soc. [Faradav 2] 77:1589(1981).Google Scholar
- 13.A. Carrington, A. D. McLachlan, “Introduction to Magnetic Resonance”, Harper and Row, New York (1967).Google Scholar
- 14.J. D. R. Clay, D. J. Murphy, The Electron Spin Resonance Spectra of Semiquinones From Some Heterocyclic Quinones, I. Chem. Soc. [Perkin 1] 1781(1984).Google Scholar
- 16.J. Hajdu, Interactions of Metal Ions with Streptonigrin and Biological Properties of the Complexes, in:“Metal Ions in Biological Systems”, H. Siegel ed., M. Dekker, Inc., New york (1985).Google Scholar