新型取代的N-(4-(2-(4-苄基哌嗪-1-基)乙氧基)phenyl)-N-甲基喹唑啉-4-胺作为强效抗肿瘤剂的合成、体外和体内评价
Synthesis, in vitro and in vivo evaluation of novel substituted N-(4-(2-(4-benzylpiperazin-1-yl)ethoxy)phenyl)-N-methyl-quinazolin-4-amines as potent antitumor agents.
作者信息
Cao Dong, Wang Xiaoyan, Lei Lei, Ma Liang, Wang Fang, Wang Chunyu, Tang Minghai, Xiang Wei, Wang Taijin, Li Hongyang, Chen Lijuan
机构信息
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center of Biotherapy, Chengdu 610041, China.
Division of Nephrology, Kidney Research Institute, West China Hospital of Sichuan University, Chengdu 610041, China.
出版信息
Bioorg Med Chem Lett. 2016 Apr 15;26(8):1931-5. doi: 10.1016/j.bmcl.2016.03.016. Epub 2016 Mar 7.
A novel series of substituted N-(4-(2-(4-benzylpiperazin-1-yl)ethoxy)phenyl)-N-methylquinazolin-4-amines were synthesized and evaluated for their in vitro antiproliferative activity. Among them, compound 7a exhibited the best potency, with IC50 values of 0.029-0.147 μM against four types of cancer cell lines. In addition, 7a was confirmed that it could arrest the cell cycle at G2/M phase and trigger apoptosis. Indirect immunofluorescence staining revealed its anti-tubulin property. Importantly, 7a significantly inhibited tumor growths in HepG2 xenograft models without causing significant loss of body weight, suggesting that 7a is a promising new anticancer agent to be developed.
合成了一系列新型的取代 N-(4-(2-(4-苄基哌嗪-1-基)乙氧基)phenyl)-N-甲基喹唑啉-4-胺，并对其体外抗增殖活性进行了评估。其中，化合物 7a 表现出最佳活性，对四种癌细胞系的 IC50 值为 0.029 - 0.147 μM。此外，证实 7a 可使细胞周期阻滞在 G2/M 期并引发凋亡。间接免疫荧光染色显示其具有抗微管蛋白特性。重要的是，7a 在 HepG2 异种移植模型中显著抑制肿瘤生长，且未导致体重显著减轻，表明 7a 是一种有前景的新型抗癌药物有待开发。
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