Cherubim P, Deady L W, Dorkos M, Quazi N H, Baguley B C, Denny W A
Chemistry Department, La Trobe University, Bundoora, Victoria, Australia.
Anticancer Drug Des. 1993 Dec;8(6):429-38.
A series of phenanthrene-based tricyclic carboxamides has been synthesized as angular analogues of the clinical acridine carboxamide DACA, and their DNA binding, in vitro cytotoxicities and in vivo antitumour activities have been investigated. The compounds fall into two broad topological classes, where the carboxamide side chain is appended either to one of the terminal rings or to the central ring. In general, compounds of the first class showed stronger DNA binding than those of the second, and were the more potent in vitro cytotoxins. However, they were considerably less effective than DACA, both as DNA binders and cytotoxins. A 1,10-phenanthrolinecarboxamide derivative showed significant in vivo activity. As a class, these fused angular tricyclic carboxamides do not show sufficiently interesting activity to warrant further studies.
已经合成了一系列基于菲的三环羧酰胺，作为临床吖啶羧酰胺DACA的角状类似物，并研究了它们的DNA结合、体外细胞毒性和体内抗肿瘤活性。这些化合物分为两大类，其中羧酰胺侧链连接到末端环之一或中心环上。一般来说，第一类化合物比第二类化合物表现出更强的DNA结合能力，并且是更有效的体外细胞毒素。然而，作为DNA结合剂和细胞毒素，它们都比DACA的效果差得多。一种1,10-菲咯啉羧酰胺衍生物表现出显著的体内活性。作为一个类别，这些稠合角状三环羧酰胺没有表现出足够有趣的活性以保证进一步研究。
