Studies on the mechanism of activation and the mutagenicity of ronidazole, a 5-nitroimidazole.
Substantial evidence implicates the obligatory nucleophilic attack by water at C4 for the elimination of the carbamate and subsequent immobilization by electrophilic attack on protein thiols. Consequently, the strong correlation between the structural requirements for protein alkylation and for mutagenicity in TA100 suggests a possible role of nucleophilic addition at C4 or at the 2-methylene carbon for the expression of mutagenicity. Further studies directed at evaluating this possibility are currently in progress.
D000478:Alkylation; D000818:Animals; D001711:Biotransformation; D008862:Microsomes, Liver / Q000378:metabolism*; D009153:Mutagens; D009593:Nitroimidazoles / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism; D051381:Rats; D012385:Ronidazole / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D009153:Mutagens; D009593:Nitroimidazoles; D011506:Proteins; D012385:Ronidazole