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Direct ESR detection of a free radical intermediate during the peroxidase-catalyzed oxidation of the antimalarial drug primaquine.

Authors
Type
Published Article
Journal
Biochemical Pharmacology
0006-2952
Publisher
Elsevier
Publication Date
Volume
37
Issue
14
Pages
2791–2797
Identifiers
PMID: 2840077
Source
Medline
License
Unknown

Abstract

Oxidation of the antimalarial primaquine by horseradish peroxidase and H2O2 was demonstrated by visible light absorption and ESR spectroscopy. Initial product analysis indicated a 15% yield of O-demethoxylation products, methanol and the quinone-imine derivative, and organic extractable polymeric material. Horseradish peroxidase was substituted by methemoglobin, and both enzymes showed greater activity at acidic pH values. During the enzymatic oxidation of primaquine, a drug-derived free radical was detected by direct ESR spectroscopy. A similar ESR spectrum was obtained during enzymatic oxidation of 6-hydroxyprimaquine at pH 9.0. Computer simulations of the ESR spectra obtained in normal and deuterated buffer indicated that the detectable free radical contains two primaquine moieties. This in vitro oxidation of primaquine to a free radical intermediate that is stable in the presence of oxygen might be considered a new mechanistic route for analyzing the pharmacological effects of primaquine.

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