Division of Organic Chemistry-I, Indian Institute of Chemical Technology, Hyderabad 500 607, India.
Eur J Med Chem. 2010 Sep;45(9):3870-84. doi: 10.1016/j.ejmech.2010.05.041. Epub 2010 Jun 1.
A series of new cinnamido-pyrrolo[2,1-c][1,4]benzodiazepine conjugates (4a-d and 5a-d) and their dimers (6a-d) have been designed, synthesized and evaluated for their biological activity. The anticancer screening of compound 4a by the NCI exhibited significant GI50 values ranging from 68 to 732 nM against 53 of 59 human cancer cell lines tested. Compounds 5a-d and 6a-d have also shown remarkable cytotoxic activity with GI50 values <0.1 microM concentrations in a large number of cell lines. Interestingly, compounds 5b and 6b have been identified as a new class of inhibitors of tubulin polymerization and their action has been rationalized by the cell cycle arrest in G0 and G2/M phase.
一系列新的肉桂酰胺-吡咯并[2,1-c][1,4]苯并二氮杂卓化合物（4a-d 和 5a-d）及其二聚体（6a-d）被设计、合成并评估了它们的生物活性。NCI 对化合物 4a 的抗癌筛选显示，对测试的 59 个人类癌细胞系中的 53 种，GI50 值范围为 68 至 732 nM。化合物 5a-d 和 6a-d 也表现出显著的细胞毒性活性，在大量细胞系中，GI50 值低于 0.1 microM 浓度。有趣的是，化合物 5b 和 6b 已被确定为微管聚合的一类新抑制剂，它们的作用通过 G0 和 G2/M 期的细胞周期停滞得到了合理化。
