title: Mutagenicity to Salmonella of four derivatives of the azo mutagen 5I: some implications for structure--activity databases and the evaluation of combinations of mutagens.
abstract: A structure--activity study is described in which four new derivatives of the potent bacterial mutagen 5-dimethylaminophenylazoindazole (5I) have been evaluated for mutagenicity to Salmonella. As expected, monodemethylation of the -NMe2 group of 5I increased its mutagenic potency while replacement of the -NMe2 with a cyclic amine reduced it. However, replacement of the aromatic indazole -NH group (of 5I) by an -NMe group (yielding NMe5I) dramatically attenuated mutagenic potency, a reduction which was both unexpected and not reversed in the monomethyl analogue (NMeMA5I). In competition experiments NMe5I had an inhibitory effect on the mutagenic potency of 5I itself and on that of the nonazo mutagen 2-acetylaminofluorene 2AAF. The results illustrate some of the problems associated with evaluating mixtures for mutagenicity and of assuming simple structure--activity relationships in the absence of relevant experimental data.
mesh_terms: D001391:Azo Compounds / Q000009:adverse effects*; D003628:Database Management Systems; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D007191:Indazoles / Q000009:adverse effects*; D009152:Mutagenicity Tests; D009153:Mutagens; D011720:Pyrazoles / Q000009:adverse effects*; D013329:Structure-Activity Relationship; D004124:p-Dimethylaminoazobenzene / Q000009:adverse effects / Q000031:analogs & derivatives*
chemical_list: D001391:Azo Compounds; D007191:Indazoles; D009153:Mutagens; D011720:Pyrazoles; C057063:1-methyl-5-(4-dimethylaminophenylazo)indazole; C057061:1-methyl-5-(4-methylaminophenylazo)indazole; C057060:5-(4-methylaminophenylazo)indazole; C057062:5-(4'-(N-piperidinyl)phenylazo)indazole; D004124:p-Dimethylaminoazobenzene