Metronidazole (Flagyl), misonidazole (Ro 07-0582), iron, zinc and sulphur compounds in cancer therapy

The nitro radiosensitizers, metronidazole and misonidazole, have been shown to react rapidly with the sulphydryl compounds cysteine and cysteamine in the presence of ferrous ions. Similar reactions occur in the presence of copper ions but these are much slower. The initial interactions of the drugs...

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Bibliographic Details
Published inBritish journal of cancer. Supplement Vol. 3; pp. 16 - 19
Main Authors Bahnemann, D, Basaga, H, Dunlop, J R, Searle, A J, Willson, R L
Format Journal Article
LanguageEnglish
Published England Nature Publishing Group 01.06.1978
Subjects
Cysteamine
Cysteine
Ferrous Compounds
Glutathione
Kinetics
Metronidazole - therapeutic use
Neoplasms - radiotherapy
Nitroimidazoles - therapeutic use
Oxidation-Reduction
Zinc
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Summary:The nitro radiosensitizers, metronidazole and misonidazole, have been shown to react rapidly with the sulphydryl compounds cysteine and cysteamine in the presence of ferrous ions. Similar reactions occur in the presence of copper ions but these are much slower. The initial interactions of the drugs and of oxygen with an iron-cysteine complex are extremely rapid: in the case of oxygen reaction half-lives of 27 ms have been measured. Misonidazole also reacts rapidly with glutathione in the presence of ferrous ions and is subsequently reduced: metronidazole is reduced only slowly if at all. These reactions, which have been found to be inhibited by high concentrations of zince ions, are discussed in the light of the known radiosensitizing and chemotherapeutic efficiencies of the nitro drugs and the side effect of peripheral neuropathy sometimes observed during their clinical use.
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ISSN:0306-9443