Characterization of free radicals produced during oxidation of etoposide (VP-16) and its catechol and quinone derivatives. An ESR Study

Biochemistry. 1989 May 30;28(11):4839-46. doi: 10.1021/bi00437a048.


Spectroscopic evidence for the radical-mediated metabolism of VP-16, VP-16 catechol, and VP-16 quinone during enzymatic oxidation and autoxidation has been obtained. Autoxidation of the catechol yields the primary semiquinone together with the primary molecular product VP-16 quinone, which subsequently undergoes hydrolytic oxidation to form secondary quinones and semiquinones. Both primary and secondary phenoxyl radicals were detected during peroxidatic oxidation of VP-16. Neither the primary nor the secondary radicals react with DNA at a detectable rate. Evidence for the production of hydroxyl radical during iron-catalyzed oxidation of VP-16 catechol was obtained. These free radical reactions may have implications for the mechanism of antitumor action of VP-16.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Catechols / metabolism*
  • Computer Simulation
  • DNA / analysis
  • DNA Damage
  • Electron Spin Resonance Spectroscopy
  • Etoposide / analogs & derivatives
  • Etoposide / metabolism*
  • Free Radicals
  • Hydroxides / analysis
  • Mathematics
  • Oxidation-Reduction
  • Phenols / analysis
  • Quinones / metabolism*


  • Catechols
  • Free Radicals
  • Hydroxides
  • Phenols
  • Quinones
  • Etoposide
  • DNA