Antineoplastic agents. 552. Oxidation of combretastatin A-1: Trapping the o-quinone intermediate considered the metabolic product of the corresponding phosphate prodrug

George Pettit, Andrew J. Thornhill, Bryan R. Moser, Fiona Hogan

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

The very unstable (<10 min at rt) o-quinone 5 derived from the vicinal diphenol anticancer drug combretastatin A-1 (1) has been obtained by careful oxidation with NaIO4 and tetrabutylammonium bromide in water/dichloromethane. Immediate reaction with phenylenediamine (6) allowed o-quinone 5 to be trapped as the stable phenazine derivative 7. For further confirmation, 5 was also captured as a dimethoxyphenylenediamine-derived phenazine (11). Both phenazines 7 and 11 significantly inhibited (ED 50 ∼0.2 μg/mL) growth of the murine P388 lymphocytic leukemia cell line and provided a new SAR insight in the combretastatin series of naturally occurring anticancer drugs.

Original languageEnglish (US)
Pages (from-to)1561-1563
Number of pages3
JournalJournal of Natural Products
Volume71
Issue number9
DOIs
StatePublished - Sep 1 2008

ASJC Scopus subject areas

  • Analytical Chemistry
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Drug Discovery
  • Complementary and alternative medicine
  • Organic Chemistry

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