Synthesis and evaluation of novel 7H-pyrrolo-[2,3-d]pyrimidine derivatives as potential anticancer agents

被引:13
|
作者
Liu, Yi-Min [1 ]
Chen, Chun-Han [2 ]
Yeh, Teng-Kuang [3 ]
Liou, Jing-Ping [1 ,4 ]
机构
[1] Taipei Med Univ, TMU Biomed Commercializat Ctr, Taipei, Taiwan
[2] Taipei Med Univ, Sch Med, Dept Pharmacol, Coll Med, Taipei, Taiwan
[3] Natl Hlth Res Inst, Inst Biotechnol & Pharmaceut Res, Zhunan Town, Miaoli County, Taiwan
[4] Taipei Med Univ, Sch Pharm, Coll Pharm, Taipei, Taiwan
关键词
apoptosis; cancer; CK1; delta; KINASE-I EPSILON; MOLECULAR SUBTYPES; BLADDER-CANCER; GROWTH; PHOSPHORYLATION; INHIBITION; CK1-DELTA; EXPRESSION; SURVIVAL; FAMILY;
D O I
10.4155/fmc-2018-0564
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Aim: Bladder cancer is a highly recurrent urologic malignancy with limited treatment approaches. Previously, we reported compound 11 is a FGFR3 inhibitor with significant antibladder cancer activity. Materials & methods: In this study, a series of 7H-pyrrolo-[2,3-d]pyrimidine derivatives were synthesized through ring formation and modification of compound 11 for anticancer activity evaluation. Results: Compound 13i is the most effective agent against human RT-112 bladder cancer cells. Notably, 13i strongly inhibits CK1 delta without affecting FGFR3 activity. We generated 13i HCl to increase solubility and showed profound cell cycle accumulation at the sub-G1 phase and apoptosis in CK1 delta-overexpressed bladder and ovarian cancer cells. Conclusion: These results indicate that compound 13i could be a lead compound for further development of novel anticancer agents. [GRAPHICS]
引用
收藏
页码:959 / 974
页数:16
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