Centre for Chemical Biology, Indian Institute of Chemical Technology (Council of Scientific and Industrial Research), Hyderabad, India.
ChemMedChem. 2011 May 2;6(5):859-68. doi: 10.1002/cmdc.201100019. Epub 2011 Apr 6.
A new class of nitrovinyl biphenyl compounds based on the structures of colchicines and allocolchicines were designed, synthesized, and shown to inhibit tubulin polymerization and cause mitotic arrest. A majority of these compounds were found to possess potent anticancer properties, with IC(50) values in the range of 0.05-7 μM, and are equally potent with colchicine in HeLa and MCF-7 cells. Compounds 14 e and 14 f inhibited tubulin assembly by more than 60 %, and flow cytometry studies indicated growth arrest of cells in the G(2)/M phase of the cell cycle in a concentration-dependent manner. Treatment of cells with 14 f resulted in upregulation of cyclin B1 and aurora kinase B mRNA levels, corresponding to growth arrest in the G(2)/M phase of the cell cycle as the mode of action.
设计、合成了一类以秋水仙碱和别秋水仙碱结构为基础的硝基乙烯联苯类新化合物，实验结果表明这些化合物能够抑制微管蛋白聚合并导致有丝分裂阻滞。大多数此类化合物具有较强的抗癌活性，在 HeLa 和 MCF-7 细胞中的半数抑制浓度（IC(50)）值在 0.05-7 μM 范围内，与秋水仙碱相当。化合物 14e 和 14f 使微管蛋白组装的抑制率超过 60%，流式细胞术研究表明，细胞生长在细胞周期的 G(2)/M 期呈浓度依赖性停滞。用 14f 处理细胞会导致细胞周期 G(2)/M 期的细胞周期蛋白 B1 和 Aurora 激酶 B mRNA 水平上调，这与作为作用模式的细胞周期 G(2)/M 期阻滞相对应。
