A novel series of benzo[6,7]indolo[3,4-c]isoquinolines - was designed by scaffold hopping of topoisomerase I inhibitor benzo[][1]benzopyrano[4,3-]indol-6(13)-ones (BBPIs), which were developed by structural modification of the natural marine product lamellarin. The unconventional pentacycle was constructed by Bischler-Napieralski-type condensation of amide and subsequent intramolecular Heck reaction. In vitro anticancer activity of the synthesized benzo[6,7]indolo[3,4-c]isoquinolines was evaluated on a panel of 39 human cancer cell lines (JFCR39). Among the compounds tested, -(3-morpholinopropyl) derivative showed the most potent antiproliferative activity, with a mean GI value of 39 nM. This compound inhibited topoisomerase I activity by stabilizing the enzyme–DNA complex.

中文翻译：

---

具有拓扑异构酶 I 抑制作用的新型苯并[6,7]吲哚并[3,4-c]异喹啉类抗癌药物的设计、合成和生物学评价

一系列新型苯并[6,7]吲哚[3,4-c]异喹啉 - 通过拓扑异构酶 I 抑制剂苯并[][1]苯并吡喃并[4,3-]吲哚-6(13)-酮的支架跳跃设计（BBPI），是通过对天然海洋产品片层蛋白进行结构修饰而开发的。非常规五环化合物是通过酰胺的 Bischler-Napieralski 型缩合和随后的分子内 Heck 反应构建的。在一组 39 种人类癌细胞系 (JFCR39) 上评估了合成的苯并[6,7]吲哚并[3,4-c]异喹啉的体外抗癌活性。在测试的化合物中，-(3-吗啉代丙基)衍生物显示出最有效的抗增殖活性，平均GI值为39 nM。该化合物通过稳定酶-DNA 复合物来抑制拓扑异构酶 I 的活性。