Singer G M, Andrews A W, Guo S M
J Med Chem. 1986 Jan;29(1):40-4. doi: 10.1021/jm00151a006.
The relative mutagenicities of substituted N-nitroso-N-benzylmethylamines have been reexamined from a quantitative structure-activity relationship point of view. Most of the compounds were mutagenic toward Salmonella typhimurium TA 1535 with Aroclor-induced male hamster liver S9 activation. The dose-response data were subjected to a multiple linear regression equation calculated in a stepwise manner, which found that the differences in mutagenicities could be explained primarily by differences in the three-bond path molecular connectivity index, with smaller contributions from sigma and pi. Moreover, a polynomial regression analysis showed that the maximum mutagenicity could be explained by an optimal amount of electron withdrawal by the substituent which would cause a weakening, or activation, of the methylene C-H bond. The possible relevance of these observations to carcinogenesis is discussed.
从定量构效关系的角度重新审视了取代N-亚硝基-N-苄基甲胺的相对诱变性。大多数化合物在Aroclor诱导的雄性仓鼠肝S9激活下对鼠伤寒沙门氏菌TA 1535具有诱变性。将剂量反应数据代入逐步计算的多元线性回归方程，发现诱变性的差异主要可以由三键路径分子连接性指数的差异来解释，σ和π的贡献较小。此外，多项式回归分析表明，最大诱变性可以用取代基最佳吸电子量来解释，该吸电子量会导致亚甲基C-H键减弱或活化。讨论了这些观察结果与致癌作用的可能相关性。
