Cyclic amines as less mutagenic replacements for dimethyl amino (--NMe2) substituents on aromatic organic compounds: implications for carcinogenicity and toxicity.
Replacement of the dimethylamino (--NMe2) group of the rodent liver carcinogens 4-dimethylaminoazobenzene (DAB) and 6-dimethylaminophenylazobenzthiazole (6BT) with a pyrrolidinyl group leads to a marked attenuation of their mutagenicity to S. typhimurium in vitro. Replacement with the 6-membered piperidinyl group leads to a virtual loss of mutagenic activity. These results are discussed within the context of a possible, albeit limited correlation between carcinogenic potency to rodents and mutagenic potency to S. typhimurium. Based on these observations, it is suggested that replacement of the --NMe2 group of a toxic/carcinogenic/mutagenic aromatic chemical by a cyclic amine substituent may produce a less toxic (etc.) analogue with similar gross molecular properties. The significance of weak (less than 2-fold increase) mutagenic responses is discussed in relation to potential carcinogenicity.
D001391:Azo Compounds / Q000633:toxicity*; D002273:Carcinogens; D004123:Dimethylamines / Q000633:toxicity; D009152:Mutagenicity Tests; D009153:Mutagens; D009154:Mutation; D010880:Piperidines / Q000633:toxicity; D011759:Pyrrolidines / Q000633:toxicity; D012486:Salmonella typhimurium / Q000187:drug effects; D013329:Structure-Activity Relationship
D001391:Azo Compounds; D002273:Carcinogens; D004123:Dimethylamines; D009153:Mutagens; D010880:Piperidines; D011759:Pyrrolidines