Shirota F N, Hanna P E
J Med Chem. 1982 May;25(5):593-5. doi: 10.1021/jm00347a020.
The effect of halogen substituents placed at the 4' position of trans-4-acetamidostilbene (1, AAS) to alter the pattern of biotransformation and thus the mutagenicity of these derivative was evaluated by comparing the mutagenic effects of 1 on Salmonella typhimurium TA-100 with the corresponding 4'-F (2), 4'-Cl (3), and 4'-Br (4) analogues. The mutagenic properties of trans-4-(N-hydroxyacetamido)stilbene (5) and its 4'-F (6), 4'-Cl (7), and 4'-Br (8) derivatives were also evaluated in this system. Both the amides (1-4) and hydroxamic acids (5-8) required the presence of a metabolic activating system prepared from hamster liver in order to produce a mutagenic effect. All of these compounds were mutagenic to A-100. Their mutagenic potencies were markedly influenced by the 4'-halogen substituents, the relative mutagenic potencies of the amides being 2 (4'-F) greater than 1 (4'-H), 3 (4'Cl) greater than 4 (4'-Br), while the hydroxamic acids followed the order of 1 (4'-H) greater than 2 (4'-F) greater than 3 (4'-Cl), 4 (4'-Br).
通过比较反式-4-乙酰氨基芪（1，AAS）对鼠伤寒沙门氏菌TA-100的诱变作用与相应的4'-氟（2）、4'-氯（3）和4'-溴（4）类似物，评估了位于反式-4-乙酰氨基芪4'位的卤素取代基改变生物转化模式进而改变这些衍生物诱变性的效果。还在该系统中评估了反式-4-（N-羟基乙酰氨基）芪（5）及其4'-氟（6）、4'-氯（7）和4'-溴（8）衍生物的诱变性。酰胺（1-4）和异羟肟酸（5-8）都需要存在由仓鼠肝脏制备的代谢活化系统才能产生诱变作用。所有这些化合物对TA-100都具有诱变性。它们的诱变效力受到4'-卤素取代基的显著影响，酰胺的相对诱变效力为2（4'-F）大于1（4'-H），3（4'-Cl）大于4（4'-Br），而异羟肟酸的顺序为1（4'-H）大于2（4'-F）大于3（4'-Cl）、4（4'-Br）。
