Palmer B D, Rewcastle G W, Atwell G J, Baguley B C, Denny W A
Cancer Research Laboratory, University of Auckland School of Medicine, New Zealand.
J Med Chem. 1988 Apr;31(4):707-12. doi: 10.1021/jm00399a003.
Structure-antitumor activity relationships are reported for a number of different examples (acridine, phenazine, anthracene, acridone, xanthenone, thioxanthenone, anthraquinone, pyridoquinazoline, dibenzodioxin, thianthrene, phenothiazine, phenoxazine, dibenzofuran, carbazole, and pyridoindole) of the general class of N-[2-(dimethylamino)ethyl] linear tricyclic carboxamides. Only the compounds containing coplanar chromophores intercalated DNA. There is an absolute requirement for an oxygen or aromatic nitrogen (possibly as hydrogen-bond acceptors) peri to the carboxamide, together with a planar ring geometry for biological activity. In addition to further delineating the nature of the pharmacophore for this class of compounds, the work has also identified dibenzo[1,4]dioxin as a novel DNA-intercalating chromophore with in vivo antitumor activity.
报道了多种不同实例（吖啶、吩嗪、蒽、吖啶酮、呫吨酮、硫代呫吨酮、蒽醌、吡啶并喹唑啉、二苯并二恶英、噻蒽、吩噻嗪、吩恶嗪、二苯并呋喃、咔唑和吡啶并吲哚）的N-[2-(二甲氨基)乙基]线性三环羧酰胺类化合物的结构-抗肿瘤活性关系。只有含有共平面发色团的化合物才能嵌入DNA。生物活性对酰胺羧基邻位的氧或芳香氮（可能作为氢键受体）以及平面环几何结构有绝对要求。除了进一步阐明这类化合物药效团的性质外，该研究还确定二苯并[1,4]二恶英是一种具有体内抗肿瘤活性的新型DNA嵌入发色团。
