Mutagenicity of structurally related phenylazo-3-pyridines in Salmonella typhimurium

Studies were conducted to explore structure-activity relationships for 4'-N,N-dimethylamino-1'-phenylazo-3-pyridine and nine structurally related compounds in Salmonella typhimurium tester strains TA1535, TA100, TA1537, TA1538, TA98. Each compound was tested for mutagenicity at five or more concentrations that varied from 10-5000 micrograms/plate. We used the standard plate test and the investigations were carried out both in the absence and presence of Aroclor-1254-induced rat-liver homogenate and the components of the NADPH-generating system. Negative response was observed for 4'-N,N-dimethylamino-1'-phenylazo-3-pyridine and five of its analogues (4'-N,N-diethylamino-1' phenylazo-3-pyridine; 4'-N,N-di-(beta-hydroxyethylamino)-1' phenylazo-3-pyridine; 4'-N-methylamino sulfonic acid-1'-phenylazo-3-pyridine; 4'-N,N-dimethylamino-6'-acetamido-1' phenylazo-3-pyridine, and 4'-N,N-di-(beta-hydroxyethylamino)-6'-methyl-l' phenylazo-3-pyridine). When S9 induced by Aroclor-1254 was present, the compound 4'-N,N-dimethylamino-6-methoxy-1' phenylazo-3-pyridine exhibited mutagenic activity in the two strains TA1538 and TA98. The compound 4',6'-diamino-3-methyl-1'-phenylazo-3-pyridine was also mutagenic, both in the presence and in the absence of S9 mix. The two compounds 4'-N,N-dimethylamino-6-butoxy-1'-phenylazo-3-pyridine and 4'N,N-di-(beta-hydroxyethylamino)-1'-phenylazo-3-[6-N,N-di-(beta- hydroxyethylamino) pyridine were either weakly mutagenic or nonmutagenic. On the basis of these data, it is concluded that the mutagenicity of phenylazo-3-pyridines, like monocyclic aromatic amines and azo dyes, is influenced by the nature of the substituent chemical groups and their positions in the molecular structure of the compounds.