Mutagenicity of nitrofurans, nitrothiophenes, nitropyrroles, nitroimidazole, aminothiophenes, and aminothiazoles in Salmonella typhimurium.
Thirty-two heterocyclic compounds, including 24 nitroheterocycles, 7 aminoheterocycles and derivatives, and 1 thiophene lacking a nitro group, were tested for mutagenic activity in Salmonella typhimurium TA 98 and TA 100. All the nitroheterocycles (11 new), including nitrofurans, nitrothiophenes, nitropyrroles, and 1 nitroimidazole, were mutagenic in TA 100; 13 were also mutagenic in TA 98. 5-Nitro-2-furoic acid, a noncarcinogen, was mutagenic in TA 100. Seven carcinogenic nitroheterocycles were mutagenic in both strains. Seven aminoheterocycles (4 new), aminothiophenes and aminothiazole derivatives, and 1 thiophene without a nitro group were not mutagenic. Both TA 98 and TA 100 were uvrB and lacked the ability of excision repair of DNA. Among the 24 mutagenic nitroheterocycles, only 13 compounds exhibited bacterial killing effects, suggesting that more than 1 mechanism may be involved in the interaction of nitroheterocycles with bacterial DNA.
D000588:Amines / Q000494:pharmacology; D004260:DNA Repair; D004269:DNA, Bacterial; D006571:Heterocyclic Compounds / Q000494:pharmacology*; D009153:Mutagens; D009574:Nitro Compounds / Q000494:pharmacology; D009581:Nitrofurans / Q000494:pharmacology; D009593:Nitroimidazoles / Q000494:pharmacology; D011758:Pyrroles; D012486:Salmonella typhimurium / Q000187:drug effects*; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000494:pharmacology; D013876:Thiophenes / Q000494:pharmacology
D000588:Amines; D004269:DNA, Bacterial; D006571:Heterocyclic Compounds; D009153:Mutagens; D009574:Nitro Compounds; D009581:Nitrofurans; D009593:Nitroimidazoles; D011758:Pyrroles; D013844:Thiazoles; D013876:Thiophenes