The effects of 4'-alkyl substituents on the mutagenic activity of 4-amino- and 4-nitrostilbenes in Salmonella typhimurium.
Six derivatives of trans-4-aminostilbene bearing different alkyl groups in the 4'-position and six of the corresponding nitro compounds were synthesized and tested for their mutagenic potency in Salmonella typhimurium strains TA98 and TA100. Regarding the test series in presence of S9-mix, maximum activity was observed for those trans-4-aminostilbenes and trans-4-nitrostilbenes bearing small alkyl substituents like methyl and ethyl. More bulky substituents reduced the mutagenic potential in the order iso-propyl<sec-butyl<tert-butyl for the aminostilbenes. The corresponding nitrostilbenes showed a similar trend under these conditions although the mutagenic activity of the tert-butyl-substituted compound was unexpectedly high in TA100. In the series without metabolic activation the nitrostilbenes showed a continuous decrease of mutagenic activity with the size of the substituents (methyl>ethyl>iso-propyl>sec-butyl>tert-butyl). These trends have been compared with quantitative structure activity relationship (QSAR) model predictions, leading to the conclusion that steric demand is an important factor for mutagenicity of substituted aminostilbenes and nitrostilbenes. The unexpected result for the tert-butyl nitrostilbene tested with metabolic activation may be attributed to a different metabolic pathway.
Ludolph
B
B
Philipps-Universität, Marburg Hans-Meerwein Strasse, 35032, Marburg, Germany.
Klein
M
M
Erdinger
L
L
Boche
G
G
D009682:Magnetic Resonance Spectroscopy; D009153:Mutagens / Q000633:toxicity*; D021281:Quantitative Structure-Activity Relationship; D012486:Salmonella typhimurium / Q000235:genetics*; D013267:Stilbenes / Q000737:chemistry / Q000633:toxicity*
D009153:Mutagens; D013267:Stilbenes