Faculty of Chemistry and Chemical Technology, University of Ljubljana, Askerceva 5, SI-1000 Ljubljana, Slovenia.
Bioorg Med Chem. 2010 Apr 1;18(7):2375-87. doi: 10.1016/j.bmc.2010.03.006. Epub 2010 Mar 10.
A series of pyrazolone-fused combretastatins and precursors were synthesized and their cytotoxicity as well as antitubulin potential was evaluated. The hydrazide 9f and the pyrazolone-fused combretastatins 12a, 12b and 12c were highly cytotoxic against various tumor cell lines including cisplatin resistant cells. The same compounds were also the best inhibitors of tubulin polymerization. Molecular modeling results showed that they bind the colchicine binding site at the tubulin heterodimer. The hydrazide 9f arrested HeLa cells in the G2/M phase of the cell cycle and strongly affected cell shape and microtubule network.
合成了一系列吡唑酮融合的康普瑞汀类似物及其前体，并评估了它们的细胞毒性和抗微管蛋白活性。酰肼 9f 和吡唑酮融合的康普瑞汀类似物 12a、12b 和 12c 对多种肿瘤细胞系具有高细胞毒性，包括顺铂耐药细胞。这些化合物也是微管蛋白聚合的最佳抑制剂。分子建模结果表明，它们结合在微管蛋白异二聚体上的秋水仙碱结合位点。酰肼 9f 将 HeLa 细胞阻滞在细胞周期的 G2/M 期，强烈影响细胞形态和微管网络。
