We designed new 3-arylthio- and 3-aroyl-1H-indole derivatives 3–22 bearing a heterocyclic ring at position 5, 6 or 7 of the indole nucleus. The 6- and 7-heterocyclyl-1H-indoles showed potent inhibition of tubulin polymerization, binding of colchicine to tubulin and growth of MCF-7 cancer cells. Compounds 13 and 19 inhibited a panel of cancer cells and the NCI/ADR-RES multidrug resistant cell line at low nanomolar concentrations. Compound 13 at 50 nM induced 77% G2/M in HeLa cells, and at 20 nM caused 50% stable arrest of mitosis. As an inhibitor of HepG2 cells (IC₅₀ = 20 nM), 13 was 4-fold superior to 19. Compound 13 was a potent inhibitor of the human U87MG glioblastoma cells at nanomolar concentrations, being nearly one order of magnitude superior to previously reported arylthioindoles. The present results highlight 13 as a robust scaffold for the design of new anticancer agents.

我们设计了新的3-芳硫基和3-芳基1 H-吲哚衍生物3–22，在吲哚核的5、6或7位带有杂环。6-和7-杂环基-1 H-吲哚显示出对微管蛋白聚合的有效抑制，秋水仙碱与微管蛋白的结合以及MCF-7癌细胞的生长。化合物13和19在低纳摩尔浓度下抑制了一组癌细胞和NCI / ADR-RES多药耐药细胞系。 浓度为50 nM的化合物13在HeLa细胞中诱导77％的G2 / M，浓度为20 nM时引起50％的有丝分裂稳定停滞。作为HepG2细胞的抑制剂（IC ₅₀  = 20 nM），13的毒性是19的4倍。化合物13是纳摩尔浓度的人U87MG胶质母细胞瘤细胞的有效抑制剂，比以前报道的芳基硫吲哚高出近一个数量级。目前的结果突出了13作为设计新抗癌药物的坚固支架。