Kaufmann Doris, Pojarová Michaela, Vogel Susanne, Liebl Renate, Gastpar Robert, Gross Dietmar, Nishino Tsuyuki, Pfaller Tobias, von Angerer Erwin
Institut für Pharmazie, Universität Regensburg, Regensburg, Germany.
Bioorg Med Chem. 2007 Aug 1;15(15):5122-36. doi: 10.1016/j.bmc.2007.05.030. Epub 2007 May 17.
Small molecules such as indoles are attractive as inhibitors of tubulin polymerization. Thus a number of 2-phenylindole-3-carbaldehydes with lipophilic substituents in both aromatic rings was synthesized and evaluated for antitumor activity in MDA-MB 231 and MCF-7 breast cancer cells. Some 5-alkylindole derivatives with a 4-methoxy group in the 2-phenyl ring strongly inhibit the growth of breast cancer cells with IC(50) values of 5-20nM. Their action can be rationalized by the cell cycle arrest in G(2)/M phase due to the inhibition of tubulin polymerization.
诸如吲哚之类的小分子作为微管蛋白聚合抑制剂很有吸引力。因此，合成了许多在两个芳环中都带有亲脂性取代基的2-苯基吲哚-3-甲醛，并在MDA-MB 231和MCF-7乳腺癌细胞中评估了其抗肿瘤活性。一些在2-苯环中带有4-甲氧基的5-烷基吲哚衍生物能强烈抑制乳腺癌细胞的生长，IC(50)值为5-20nM。由于其对微管蛋白聚合的抑制作用，它们在G(2)/M期使细胞周期停滞，从而解释了其作用机制。
