Mutagenicity of pyridine- and quinoline-carbohydroxamic acid derivatives.
11 pyridine- and 6 quinoline-carbohydroxamic acids were tested for mutagenicity on Salmonella typhimurium TA100 and TA98. The results are compared with those obtained for benzohydroxamic acid and 4 naphthohydroxamic acids. Most of them were mutagenic on both these tester strains. Of the pyridine derivatives, pyridine-2-carbohydroxamic acid was the most potent mutagen. Quaternarization of the pyridine-ring nitrogen prevented the induction of mutation to a marked extent. Among the quinoline derivatives, quinoline-6-carbohydroxamic acid showed potent mutagenicity similar to that of 2-naphthohydroxamic acid. The present study supports the proposal made previously that the mechanism for mutagenicity of hydroxamic acids involves Lossen rearrangement of the acid conjugates produced by enzymic acylation (or perhaps phosphorylation or sulfation) of the hydroxamic acids, followed by carbamoylation of the target molecule in the cell by the resultant isocyanate. The multiplicity of factors determining the mutagenic potency of hydroxamic acids is discussed.
D006877:Hydroxamic Acids / Q000633:toxicity*; D009152:Mutagenicity Tests; D009153:Mutagens; D009154:Mutation; D011725:Pyridines / Q000633:toxicity*; D011804:Quinolines / Q000633:toxicity*; D012486:Salmonella typhimurium / Q000187:drug effects; D013045:Species Specificity; D013329:Structure-Activity Relationship
D006877:Hydroxamic Acids; D009153:Mutagens; D011725:Pyridines; D011804:Quinolines