Semi-quinone formation from the catechol and ortho-quinone metabolites of the antitumor agent VP-16-213

J. M S van Maanen, U. H. Verkerk, J. Broersen, M. V M Lafleur, J. De Vries, J. Retel, H. M. Pinedo

Research output: Contribution to journalArticle

Abstract

The catechol metabolite of the antitumor agent VP-16-213 and the ortho-quinone of VP-16-213 - a secondary metabolite formed from the catechol ... easily undergo auto-oxidation into a free radical at pH ≤ 7.4. By elevation of the pH from 7.4 to 10, an increase in the production of the free radical was observed, which was accompanied by the formation of products with higher hydrophylicity than the catechol and ortho-quinone, as found by HPLC-analysis. The hypefine structure of the free radical indicates that it is the semi-quinone radical of VP-16-213. At pH 12.5 a secondary radical is formed from the catechol and the ortho-quinone of VP-16-213 besides the semi-quinone radical. One-electron oxidation of the catechol with horseradish peroxidase/hydrogen peroxide resulted in the formation of the same radical as observed under alkaline conditions and subsequent oxidation to the ortho-quinone. If the ortho-quinone was incubated with NADPH cytochrome P-450 reductase, a free radical was detected by spin-trapping with POBN, but not without spin-trapping. Studies on inactivation of πX174 DNA by the system ortho-quinone of VP-16-213/NADPH cytochrome P-450 reductase suggest that the semi-quinone radical may play a role in the process of inactivation of DNA.

Original languageEnglish (US)
Pages (from-to)371-384
Number of pages14
JournalFree Radical Research
Volume4
Issue number6
DOIs
Publication statusPublished - 1988
Externally publishedYes

    Fingerprint

Keywords

  • Catechol
  • Free. radical
  • Ortho-quinone
  • Semi-quinone
  • VP-16-213

ASJC Scopus subject areas

  • Biochemistry

Cite this

van Maanen, J. M. S., Verkerk, U. H., Broersen, J., Lafleur, M. V. M., De Vries, J., Retel, J., & Pinedo, H. M. (1988). Semi-quinone formation from the catechol and ortho-quinone metabolites of the antitumor agent VP-16-213. Free Radical Research, 4(6), 371-384. https://doi.org/10.3109/10715768809066905