Marciani Magno S, Terbojevich M, Dall'Acqua F, Gia O, Baccichetti F, Carlassare F, Bordin F
Farmaco Sci. 1979 Sep;34(9):759-73.
Four compounds having a molecular structure analogous to that of tilorone and tilorone itself, taken as a reference compound, were examined for complex formation ability with DNA. While the association constants of the various complexes were almost the same, the r values in saturation conditions (that is the highest number of molecules bound per nucleotide of DNA) increased with the size of the planar moiety or with the length of the two basic side chains of the molecules. Concerning the structure of the complexes, it was evidenced by means of flow dichroism measurements that the non-covalent binding to DNA occurs via an intercalative mode. Moreover, it was observed that by decreasing the ionic strength, the affinity of the drugs for the macromolecule increases, indicating that in complex formation, electrostatic forces exerted between the DNA phosphate residues and the positively charged nitrogen of the side chains of the drugs are involved. It seems also possible that, in this condition, and in the presence of high concentrations of the drug, a secondary binding consisting only of electrostatic interactions outside of the helix takes place. In connection with the complexing ability with DNA, the examined compounds proved able to inhibit DNA and RNA synthesis in Ehrlich ascites tumor cells. A correlation was found between complexing ability and inhibitory activity on nucleic acid synthesis.
研究了四种分子结构与泰勒菌素类似的化合物以及作为参考化合物的泰勒菌素本身与DNA形成复合物的能力。虽然各种复合物的缔合常数几乎相同，但饱和条件下的r值（即每核苷酸DNA结合的分子数最高值）随着平面部分的大小或分子两条碱性侧链的长度增加而增大。关于复合物的结构，通过流动二色性测量证明，与DNA的非共价结合通过插入模式发生。此外，观察到通过降低离子强度，药物对大分子的亲和力增加，这表明在复合物形成过程中，涉及DNA磷酸残基与药物侧链带正电荷的氮之间施加的静电力。在这种情况下，并且在高浓度药物存在下，似乎也可能发生仅由螺旋外的静电相互作用组成的二级结合。关于与DNA的络合能力，所研究的化合物被证明能够抑制艾氏腹水瘤细胞中的DNA和RNA合成。发现络合能力与核酸合成抑制活性之间存在相关性。
