Formation of an amino reduction product of metronidazole in bacterial cultures: lack of bactericidal activity.
To investigate whether the amino reduction product of metronidazole has antibacterial activity, 5-amino-1-beta-hydroxyethyl-2-methylimidazole (AMN) was synthesized and tested against Bacteroides fragilis and Escherichia coli strain SR58, both of which are known to be sensitive to metronidazole. Neither of these strains was found to be sensitive either to AMN or to the equivalent amine derived from dimetridazole, 5-amino-1,2-dimethylimidazole. Both of these amines are relatively stable in the presence of bacteria, making it possible to examine the bacterial reduction of radiolabeled metronidazole in the presence of AMN. This experiment indicated that at least 17% of the metronidazole that disappeared under the reducing conditions of the bacterial medium was converted to AMN. We conclude, therefore, that AMN forms during the activation of metronidazole by bacterial reduction but is not a bactericidal form of metronidazole.
D001441:Bacteroides fragilis / Q000187:drug effects; D001711:Biotransformation; D004926:Escherichia coli / Q000187:drug effects; D007093:Imidazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D008795:Metronidazole / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism* / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D010084:Oxidation-Reduction
D007093:Imidazoles; D008795:Metronidazole; C050486:5-amino-1,2-dimethylimidazole; C035820:1-(2-hydroxyethyl)-2-methyl-5-aminoimidazole