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 synthesiz ed and tested for their mutagenic potency in Salmonella typhimurium strains TA98 and TA100. Regarding the test series in presence of SE-mix, maximum a ctivity was observed for those trans-4-aminostilbenes and trans-4-nitrostil benes bearing small alkyl substituents like methyl and ethyl. More bulky su bstituents reduced the mutagenic potential in the order iso-propyl < sec-bu tyl < tert-butyl for the aminostilbenes. The corresponding nitrostilbenes s howed a similar trend under these conditions although the mutagenic activit y of the tert-butyl-substituted compound was unexpectedly high in TA100. In the series without metabolic activation the nitrostilbenes showed a contin uous decrease of mutagenic activity with the size of the substituents (meth yl > ethyl > iso-propyl > sec-butyl > tert-butyl). These trends have been c ompared with quantitative structure activity relationship (QSAR) model pred ictions, leading to the conclusion that steric demand is an important facto r for mutagenicity of substituted aminostilbenes and nitrostilbenes. The un expected result for the tert-butyl nitrostilbene tested with metabolic acti vation may be attributed to a different metabolic pathway. (C) 2001 Elsevie r Science B.V. All rights reserved.