N-Acyloxy-N-alkoxyamides are direct-acting mutagens in S. typhimurium TA100 and TA98. A reliable QSAR for their activity in TA100 has been developed, which indicates reversible intercalation into the DNA helix through naphthalene substituents. In this paper, we show that fluorene as a substituent does not facilitate intercalation while fluorenone does, although the efficacy is determined by the position of substitution on the fluorenone as well as the N-acyloxy-N-alkoxyamide side chain. Where intercalation is evident, the increased binding to DNA is similar to that of naphthalene and is worth the equivalent of ca four LogP hydrophobicity units. 4-Substituted fluorenones, where the anomeric amide group is in the bay region do not intercalate, which is attributed to the requirement for a weaker edge-on, rather than an end-on intercalation. Mutagencity in S. typhimurium TA98, which detects frame shifts through intercalation, supports the findings. Fluorene appears not to intercalate, which points to the fact that the charge delocalised 2-fluorenylnitrenium ion, the ultimate metabolite from 2-aminofluorene (AF) and 2-acetylaminofluorene (AAF) is the itercalating agent responsible for frameshift mutations leading to their carcinogenicity.

N-酰氧基-N-烷氧基酰胺是鼠伤寒沙门氏菌TA100和TA98中的直接作用诱变剂。已经开发了一种可靠的 QSAR，用于它们在 TA100 中的活性，这表明通过萘取代基可逆嵌入 DNA 螺旋中。在本文中，我们表明芴作为取代基不会促进嵌入，而芴酮可以，尽管功效取决于芴酮上的取代位置以及N-酰氧基-N-烷氧基酰胺侧链。在嵌入明显的情况下，与 DNA 的结合增加与萘的结合相似，相当于约4 Log P疏水性单位。4-取代的芴酮，其中异头酰胺基团位于湾区不嵌入，这归因于需要较弱的边缘插入，而不是末端插入。鼠伤寒沙门氏菌TA98 的致突变性，通过插入检测框架偏移，支持了这些发现。芴似乎没有嵌入，这表明电荷离域的 2-芴基氮鎓离子是 2-氨基芴 (AF) 和 2-乙酰氨基芴 (AAF) 的最终代谢物，是导致移码突变导致其致癌性的插入剂。