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Mechanism of Metabolic Activation of Nitroimidazoles

  • Anthony Y. H. Lu
  • Peter G. Wislocki
Part of the NATO ASI Series Advanced Science Institutes Series book series (NSSA, volume 202)

Abstract

5-Nitroimidazoles are highly effective therapeutic agents (1) against a variety of anaerobic bacteria and protozoa (Table 1). For this reason, the medicinal use of these agents has been explored in humans and in food-producing animals. For example, metronidazole (1-hydroxyethyl-2-methyl-5-nitroimidazole) is used in human therapy because of its proven activity against trichomoniasis as well as its prophylactic and therapeutic efficacy against a wide range of gram positive anaerobic bacteria (2, 3). Ronidazole [l-methyl-5-nitroimidazole-2-yl)-methylcarbamate] is a highly effective drug for the treatment of turkey blackhead and swine dysentery. However, as a class, 5-nitroimidazoles are genotoxic. Various studies have demonstrated the critical importance of the reduction of the nitro group in their cytotoxicity, mutagenicity, carcino-genicity and interaction with DNA (2–5). To investigate the mechanism of metabolic activation of 5-nitroimidazoles, the covalent binding of ronidazole to proteins has been extensively studied in rats.

Keywords

Nitro Group Covalent Binding Reactive Metabolite Protein Adduct Carbamic Acid 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • Anthony Y. H. Lu
    • 1
  • Peter G. Wislocki
    • 1
  1. 1.Merck Sharp & Dohme Research LaboratoriesRahwayUSA

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