Development of low toxicity topoisomerase inhibitor (anticancer medicine) with treatment and protective efficacy

制备了三没食子酰氨基苯（TGBA）衍生物，并测定了它们对人拓扑异构酶（topo）I和II的抑制活性。TGBA衍生物中含有大量的OH基团，对拓扑异构酶I和拓扑异构酶II有较强的抑制作用。与喜树碱和依托泊苷的抑制作用不同，TGBA衍生物在topo-DNA复合物形成之前就直接抑制topo Ⅰ和Ⅱ的活性，而不稳定DNA-topo可切割复合物。在对多种肿瘤细胞株的抗癌作用中，TGBA衍生物对脑和肺癌细胞株显示出细胞生长的抑制作用。这些结果表明，TGBA衍生物是一种新型的拓扑结构抑制型抗癌药物，有望成为抗脑癌和肺癌药物的先导化合物。

Tris(galloylamino)benzene (TGBA) derivatives were prepared and their inhibitory activities were measured against human topoisomerase (topo) I and II. TGBA derivatives with many OH group showed strong inhibition against the topo I and II. Unlike camptothecin and etoposide which are the inhibitors, TGBA derivatives directly inhibited the activities of topo I and II in earlier step than the formation of topo-DNA complex, which did not stabilized DNA-topo cleavable complex. In anti cancer effects for various cancer cell lines, TGBA derivatives showed the inhibitory effects of cell growth for brain and lung cancer cell lines. These results suggests that TGBA derivatives are an anticancer drug by topo inhibition of a new type, and could be candidates as lead compounds of anti-brain and anti-lung cancer drugs.