Banik B K, Becker F F
The University of Texas, M. D. Anderson Cancer Center, Department of Molecular Pathology, Houston 77030, USA.
Bioorg Med Chem. 2001 Mar;9(3):593-605. doi: 10.1016/s0968-0896(00)00297-2.
A large number of diamides and diamines were synthesized using 6-amino chrysene and 1-amino pyrene as starting materials. A structure activity study with cis-platinum as internal control against animal and human tumor lines was carried out in vitro. This study indicated that the in vitro cytotoxicity toward these lines depends on the functionality present in the molecules. The diamino compounds were found to be more potent than the diamides, and these were equally active irrespective of the end heterocyclic group, whereas the activity of the diamides was strongly dependent on the terminal unit. In general, the diamides containing chrysene as the chromophore were more active than those with a pyrene ring. The size of the end heterocyclic ring, along with the nature of the spacer connecting the polycyclic ring to the heterocyclic ring, seemed to affect the biological activity in certain cell lines. Hemolysis experiments on a lead compound established that it had activities similar to those described for membrane-stabilizing agents. This agent also demonstrated the capacity to produce differentiation in leukemia cell lines.
以6-氨基并四苯和1-氨基芘为起始原料合成了大量的二酰胺和二胺。以顺铂作为内部对照，针对动物和人类肿瘤细胞系进行了体外结构活性研究。该研究表明，这些细胞系的体外细胞毒性取决于分子中存在的官能团。发现二胺化合物比二酰胺更具活性，并且无论末端杂环基团如何，它们的活性都相同，而二酰胺的活性强烈依赖于末端单元。一般来说，以并四苯为发色团的二酰胺比含有芘环的二酰胺更具活性。末端杂环的大小以及连接多环与杂环的间隔基的性质，似乎会影响某些细胞系中的生物活性。对一种先导化合物进行的溶血实验表明，它具有与膜稳定剂所描述的活性相似的活性。该药物还表现出诱导白血病细胞系分化的能力。
