College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao 266042, China.
Eur J Med Chem. 2011 Sep;46(9):4056-61. doi: 10.1016/j.ejmech.2011.06.004. Epub 2011 Jun 14.
In an attempt to generate compounds with superior bioactivity and reduced toxicity, a series of derivatives of deoxypodophyllotoxin were synthesized by reacting 4'-demethyl-4-deoxypodophyllotoxin with substituted piperazines or their amino acid amides. The cytotoxic activity of these compounds against three human cancer cell lines was evaluated. We found that p-nitrophenylpiperazine substitution (Compound 8b) led to an increase in the potency of the compound. Compound 8b exhibited the most potent cytotoxicity against A-549, HeLa and SiHa cells (IC(50) values were 0.102, 0.180 and 0.0195 μM, respectively). In addition, flow cytometric analysis showed that 8b induced cell cycle arrest in the G1 phase accompanied by apoptosis in A-549 cells.
为了生成具有更高生物活性和更低毒性的化合物，我们通过将 4′-去甲-4-去氧鬼臼毒素与取代的哌嗪或其氨基酸酰胺反应，合成了一系列去氧鬼臼毒素的衍生物。我们评估了这些化合物对三种人癌细胞系的细胞毒性活性。我们发现对-硝基苯哌嗪取代（化合物 8b）会增加化合物的效力。化合物 8b 对 A-549、HeLa 和 SiHa 细胞表现出最强的细胞毒性（IC50 值分别为 0.102、0.180 和 0.0195 μM）。此外，流式细胞术分析表明，8b 诱导 A-549 细胞中的细胞周期停滞在 G1 期，并伴有细胞凋亡。
