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 Citations (Scopus)

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 2008

Fingerprint

Prodrugs
Antineoplastic Agents
Phosphates
Phenazines
Lymphoid Leukemia
Phenylenediamines
Oxidation
Methylene Chloride
Pharmaceutical Preparations
Cells
Derivatives
Cell Line
Water
Growth
phenazine
benzoquinone
combretastatin A-1
tetrabutylammonium
combretastatin

ASJC Scopus subject areas

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

Cite this

Antineoplastic agents. 552. Oxidation of combretastatin A-1 : Trapping the o-quinone intermediate considered the metabolic product of the corresponding phosphate prodrug. / Pettit, George; Thornhill, Andrew J.; Moser, Bryan R.; Hogan, Fiona.

In: Journal of Natural Products, Vol. 71, No. 9, 09.2008, p. 1561-1563.

Research output: Contribution to journalArticle

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