Comparison of the genetic activity of 5-nitroimidazole derivatives in Escherichia coli, Neurospora crassa, Saccharomyces cerevisiae and Drosophila melanogaster.
5-nitroimidazoles, including metronidazole (compound 1) and 3 analogues (compounds 2, 3 and 4) of actual or potential chemotherapeutic use were assayed for genetic activity in test systems detecting forward and back mutations in Escherichia coli K-12/343/113, forward mutations in Neurospora crassa heterokaryon 12, mitotic gene conversion in the heteroallelic diploid yeast strain Saccharomyces cerevisiae D4 and sex-linked recessive lethals in Drosophila melanogaster. Whereas metronidazole exhibits moderate mutagenic activity in E. coli, two of the analogues, compounds 2 and 3 are strongly mutagenic even at concentrations that do not inactive the colony forming ability of the cells. The analogue compound 4 does not show any effect toward E. coli under the present experimental conditions. Similar results were obtained with N. crassa, with S. cerevisiae and with Drosophila in which compound 2 exhibits the highest effect, while compound 4 is non-mutagenic in all assays. These biological effects have been partly explained on the basis of differences in the chemical structure of the compounds.
D000818:Animals; D004331:Drosophila melanogaster / Q000187:drug effects / Q000235:genetics; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics; D008297:Male; D008795:Metronidazole / Q000031:analogs & derivatives / Q000494:pharmacology; D009153:Mutagens; D009492:Neurospora crassa / Q000187:drug effects / Q000235:genetics; D009593:Nitroimidazoles / Q000494:pharmacology*; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics; D013045:Species Specificity; D013329:Structure-Activity Relationship
D009153:Mutagens; D009593:Nitroimidazoles; D008795:Metronidazole