Design, synthesis and biological evaluation of pyrimidine derivatives as novel CDK2 inhibitors that induce apoptosis and cell cycle arrest in breast cancer cells

被引：32

作者：

Wang, Yiting ^{[1
]}

Chen, Yanmei ^{[1
]}

Cheng, Xiaoling ^{[1
]}

Zhang, Ke ^{[1
]}

Wang, Hangyu ^{[1
]}

Liu, Bo ^{[1
]}

Wang, Jinhui ^{[1
,2
,3
]}

机构：

[1] Shihezi Univ, Coll Pharm, Minist Educ, Key Lab Xinjiang Phytomed Resource & Utilizat, Shihezi 832002, Peoples R China

[2] Xinjiang Med Univ, Sch Pharm, Urumqi 830054, Peoples R China

[3] Harbin Med Univ, Coll Pharm, Harbin 150081, Heilongjiang, Peoples R China

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2018年 / 26卷 / 12期

关键词：

CDK2; inhibitor; Cell cycle arrest; Apoptosis; Anti-proliferative activity; DEPENDENT KINASES; POTENT; PROGRESSION; STATISTICS; THERAPY; TUMORS;

D O I：

10.1016/j.bmc.2018.05.024

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Cyclin-dependent kinase 2 ( CDK2) plays a key role in eukaryotic cell cycle progression which could facilitate the transition from G1 to S phase. The dysregulation of CDK2 is closely related to many cancers. CDK2 is utilized as one of the most studied kinase targets in oncology. In this article, 24 benzamide derivatives were designed, synthesized and investigated for the inhibition activity against CDK2. Our results revealed that the compound 25 is a potent CDK2 inhibitor exhibiting a broad spectrum anti-proliferative activity against several human breast cancer cells. Additionally, compound 25 could block cell cycle at G0 or G1 and induce significant apoptosis in MDA-MB-468 cells. These findings highlight a rationale for further development of CDK2 inhibitors to treat human breast cancer.

引用

页码：3491 / 3501

页数：11

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