Antitrichomonad action, mutagenicity, and reduction of metronidazole and other nitroimidazoles.
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 (KV(1)) and Trichomonas vaginalis (ATCC 30001) for mutagenicity on a nitroreductase-positive (TA 100) and a nitroreductase-deficient (TA 100-FR(1)) strain of Salmonella typhimurium, as well as for the reducibility of the nitro group by T. foetus homogenates. Compounds with activity <1% of that of metronidazole are regarded as inactive. All antitrichomonad compounds induce mutations and can be reduced. S. typhimurium TA 100 gave mutations under both aerobiosis and anaerobiosis; TA 100-FR(1), 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.
D000332:Aerobiosis; D000693:Anaerobiosis; D000994:Antitrichomonal Agents; D004579:Electron Transport / Q000187:drug effects; D008795:Metronidazole / Q000378:metabolism / Q000494:pharmacology*; D009153:Mutagens; D009593:Nitroimidazoles / Q000378:metabolism / Q000494:pharmacology*; D010084:Oxidation-Reduction; D012486:Salmonella typhimurium / Q000187:drug effects; D014246:Trichomonas vaginalis / Q000187:drug effects / Q000378:metabolism; D014318:Tritrichomonas / Q000187:drug effects / Q000378:metabolism
D000994:Antitrichomonal Agents; D009153:Mutagens; D009593:Nitroimidazoles; D008795:Metronidazole