Antitrichomonad Action, Mutagenicity, and Reduction of Metronidazole and Other Nitroimidazoles

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Abstract
Twelve 4- and 5-nitroimidazole derivatives, including metronidazole and two of its metabolites, tinidazole, dimetridazole, and nimorazole, were tested for antitrichomonad action on Tritrichomonas foetus (KV1) and Trichomonas vaginalis (ATCC 30001) for mutagenicity on a nitroreductase-positive (TA 100) and a nitroreductase-deficient (TA 100-FR1) strain of Salmonella typhimurium, as well as for the reducibility of the nitro group by T. foetus homogenates. Compounds with activity S. typhimurium TA 100 gave mutations under both aerobiosis and anaerobiosis; TA 100-FR1, however, gave mutations only under anaerobiosis. Certain compounds that are reducible, and the nonreducible derivatives, were inactive. Metronidazole and its inactive 4-nitro analogue were reduced in a four-electron process in ferredoxin- or methyl viologen-mediated reactions with the same velocity. The results underscore the role of the reduction of the nitro group in the antitrichomonad and in the mutagenic activity of nitroimidazoles.

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