Structure-activity relationships of nitro and methyl-nitro derivatives of indoline, indole, indazole and benzimidazole in Salmonella typhimurium.
The mutagenic activities of eleven nitro derivatives and eleven N-methyl-nitro derivatives of indoline, indole, indazole and benzimidazole were investigated in Salmonella TA98 and TA100. The presence of a nitro group at C4 or C7 resulted in only weakly or nonmutagenic compounds, while a nitro group at C2, C5 or C6 usually resulted in measurable mutagenic activity in the non-N-methylated compounds. Methylation of a ring nitrogen usually reduced the mutagenic activity of these nitroheterocyclics except 2-nitro-benzimidazole, which resulted in a better than 300-fold increase in mutagenic activity. A proposed mechanism for the increased mutagenic activity obtained by methylation of imidazole nitrogens may provide insights into the reasons for the potent mutagenicities observed for several similarly methylated cooked-food mutagens.
D001562:Benzimidazoles / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology*; D007191:Indazoles / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology*; D008745:Methylation; D009152:Mutagenicity Tests; D009574:Nitro Compounds / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology*; D012486:Salmonella typhimurium / Q000187:drug effects; D013329:Structure-Activity Relationship
D001562:Benzimidazoles; D007093:Imidazoles; D007191:Indazoles; D007211:Indoles; D009574:Nitro Compounds; D011720:Pyrazoles; C031000:benzimidazole