One-pot synthesis and antiproliferative activity of novel 2,4-diaminopyrimidine derivatives bearing piperidine and piperazine moieties.
One-pot synthesis and antiproliferative activity of novel 2,4-diaminopyrimidine derivatives bearing piperidine and piperazine moieties.
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DOI：
10.1016/j.ejmech.2014.07.017
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发表时间：
2014-09
影响因子：
6.7
通讯作者：
Wei Ma;Hai-Kui Yang;Mengjin Hu;Qian Li;Tian-Zhu Ma;Zhong-Zhen Zhou;Ruiling Liu;Wen-wei You
中科院分区：
文献类型：
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作者：
Wei Ma;Hai-Kui Yang;Mengjin Hu;Qian Li;Tian-Zhu Ma;Zhong-Zhen Zhou;Ruiling Liu;Wen-wei You
采用高效的一锅法合成了一系列含有哌啶和哌嗪基团的新型2,4-二氨基嘧啶。生物实验表明，化合物27和28对HepG2、A549、MDA-MB-231和MCF-7四种人癌细胞的抗肿瘤活性明显高于阳性对照氟尿嘧啶。特别是化合物28对MDA-MB-231和A549细胞增殖的抑制作用比氟尿嘧啶提高了2倍，ic50值分别为7.46 μM和12.78 μM。进一步的流动激活细胞分选分析显示，最有希望的化合物28在MDA-MB-231细胞中以剂量依赖的方式对G2/M细胞周期阻滞有显著影响。
A series of novel 2,4-diaminopyrimidines containing piperidine and piperazine moieties were synthesizedviaan efficient one-pot methodology. The bioassay tests demonstrated that compounds27and28displayed much stronger antitumor activities against four human cancer cell lines (HepG2, A549, MDA-MB-231 and MCF-7) than positive control fluorouracil. Particularly, compound28showed a two-fold improvement compared to fluorouracil in inhibiting MDA-MB-231 and A549 cell proliferation with IC50values of 7.46 and 12.78 μM, respectively. Further flow-activated cell sorting analysis revealed that the most promising compound28displayed a significant effect on G2/M cell-cycle arrest in a dose-dependent manner in MDA-MB-231 cells.