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

制备了三（没食子胺）苯（TGBA）衍生物，并测定了其对人拓扑异构酶（topo） I和II的抑制活性。含有较多OH基团的TGBA衍生物对topo I和topo II具有较强的抑制作用。与喜树碱和依托泊苷作为抑制剂不同，TGBA衍生物在形成拓扑- dna复合物之前就直接抑制了拓扑I和拓扑II的活性，这并没有稳定dna -拓扑可切割复合物。在对多种肿瘤细胞系的抗癌作用中，TGBA衍生物对脑癌和肺癌细胞系显示出抑制细胞生长的作用。这些结果表明，TGBA衍生物是一种通过拓扑抑制的新型抗癌药物，可以作为抗脑癌和抗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.