Malesani G, Chiarelotto G, Ferlin M G, Bordin F, Baccichetti F, Carlassare F, Vedaldi D, Dall'Acqua F
Farmaco Sci. 1984 Nov;39(11):925-34.
With the aim of obtaining new bifunctional intercalators for DNA, a new series of bis-pyridoquinolines were synthesized by joining two tricyclic planar moieties through a flexible chain. For preparing the corresponding potential monofunctional intercalators also a series of mono-pyridoquinolines were prepared by chemical synthesis by joining the same chromophore with a flexible side-chain. The melting profiles of the complexes between two bis-pyridoquinolines and DNA showed two different thermal transitions supporting the bis-intercalation of the ligand with the macromolecule. On the other hand, two mono-pyridoquinolines showed only one transition in the melting profile indicating a behaviour consistent with a mono-intercalation. The antiproliferative activity was tested in terms of DNA synthesis inhibition in Ehrlich ascite tumor cells; the examined bis-intercalating agent showed to be much more active than the tested mono-intercalating compound.
为了获得新型的用于DNA的双功能嵌入剂，通过一个柔性链连接两个三环平面部分，合成了一系列新的双吡啶喹啉。为了制备相应的潜在单功能嵌入剂，还通过化学合成将相同的发色团与柔性侧链连接，制备了一系列单吡啶喹啉。两种双吡啶喹啉与DNA之间复合物的熔解曲线显示出两种不同的热转变，支持配体与大分子的双嵌入。另一方面，两种单吡啶喹啉在熔解曲线中仅显示出一个转变，表明其行为与单嵌入一致。通过检测艾氏腹水瘤细胞中的DNA合成抑制来测试抗增殖活性；所检测的双嵌入剂显示出比所测试的单嵌入化合物活性高得多。
