Synthesis, in vitro and in vivo anticancer activities of novel 4-substituted 1,2-bis(4-chlorophenyl)-pyrazolidine-3,5-dione derivatives
Synthesis, in vitro and in vivo anticancer activities of novel 4-substituted 1,2-bis(4-chlorophenyl)-pyrazolidine-3,5-dione derivatives
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DOI：
10.1039/c5md00240k
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发表时间：
2015-10
期刊：
影响因子：
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通讯作者：
Xuyao Zhang;Guo Yifei;Chen Ting;Dongxiao Yang;Xi-Xin Wang;Bailing Jiang;Kun-Peng Shao;Wen-en Zhao;Cong Wang;Jun-wei Wang;Qiurong Zhang;Hong-min Liu
中科院分区：
文献类型：
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作者：
Xuyao Zhang;Guo Yifei;Chen Ting;Dongxiao Yang;Xi-Xin Wang;Bailing Jiang;Kun-Peng Shao;Wen-en Zhao;Cong Wang;Jun-wei Wang;Qiurong Zhang;Hong-min Liu
为了开发高效、选择性的抗癌药物，设计并合成了一系列新型的4-取代1，2-bis(4-chlorophenyl)-pyrazolidine-3，5-dione衍生物。所有这些化合物都被评估了它们对四种人类癌细胞株的抗增殖活性。其中化合物4u作用最强，IC50值在5.1~10.1μM之间。流式细胞仪和免疫印迹分析显示，化合物4u通过激活caspase9/3诱导MGC803细胞早期凋亡。此外，化合物4u有效地抑制了体内人胃癌细胞的生长，且无明显毒副作用。我们的研究结果表明，化合物4u可能作为靶向实体瘤的先导化合物。
To develop potent and selective anticancer agents, a series of novel 4-substituted 1,2-bis(4-chlorophenyl)-pyrazolidine-3,5-dione derivatives were designed and synthesized. All the compounds were evaluated for their antiproliferative activities against a panel of four human cancer cell lines. Among them, compound 4u is the most potent, exhibiting IC50 values ranging from 5.1 to 10.1 μM. Flow cytometry and western blot analyses revealed that treatment of MGC-803 cells with compound 4u induces early cellular apoptosis via activation of caspases-9/3. Furthermore, compound 4u effectively reduced the tumor growth exhibited by human gastric cancer cells in vivo without obvious adverse side effects. Our findings indicate that compound 4u may serve as a lead compound to target solid tumors.