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

doi:10.1021/np800179g

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 journal › Article › peer-review

28 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 language	English (US)
Pages (from-to)	1561-1563
Number of pages	3
Journal	Journal of Natural Products
Volume	71
Issue number	9
DOIs	https://doi.org/10.1021/np800179g
State	Published - Sep 2008

ASJC Scopus subject areas

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

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

Research output: Contribution to journal › Article › peer-review

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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.",

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

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