The direct-acting mutagenicity of nitroimidazo[2,1-b]thiazoles in Salmonella typhimurium.
A series of nitroimidazo[2,1-b]thiazole derivatives was investigated for direct-acting mutagenic potency with the Salmonella assay. All of the nine derivatives tested were mutagenic. The compounds induced predominantly base displacements resulting in frame-shift mutations. The mutagenic activity did not require the S9 fraction but was largely dependent on "classical" bacterial nitroreductase. The primary basis of the mutagenic activity of nitroimidazo[2,1-b]thiazoles appears to be a reduction of the nitro-function to the corresponding hydroxylamine. Mutagenicity seems to be paralleled by an increase of the nitro groups: dinitroderivatives were more active than nitroderivatives. Other electrophiles and sterically constrained nitro groups could account for differences in genotoxicity.
D009152:Mutagenicity Tests / Q000379:methods; D009153:Mutagens / Q000494:pharmacology*; D009154:Mutation; D009593:Nitroimidazoles / Q000494:pharmacology*; D012486:Salmonella typhimurium / Q000187:drug effects; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000494:pharmacology*
D009153:Mutagens; D009593:Nitroimidazoles; D013844:Thiazoles