Synthesis and mechanism of action of new purine derivatives against triple negative breast cancer

被引：2

作者：

Zhang, Qian ^{[1
]}

Sun, Guoyang ^{[1
]}

Huang, Yuna ^{[1
]}

Cui, Shanshan ^{[1
]}

Li, Tingshen ^{[1
]}

Zhao, Lianbo ^{[1
]}

Lu, Kui ^{[1
]}

Yu, Peng ^{[1
]}

Zhang, Yongmin ^{[2
]}

Galons, Herve ^{[1
,3
]}

Oumata, Nassima ^{[3
]}

Teng, Yuou ^{[1
,3
]}

机构：

[1] Tianjin Univ Sci & Technol, Cooperat Base Food Nutr Safety & Med Chem, China Int Sci & Technol, Tianjin 300457, Peoples R China

[2] Sorbonne Univ, Inst Parisien Chim Mol, CNRS, UMR8232, 4 Pl Jussieu, F-75005 Paris, France

[3] Univ Paris Cite, 4 Ave Observ, F-75006 Paris, France

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2023年 / 261卷

基金：

中国国家自然科学基金;

关键词：

TNBC; CLKs; CDK7; MDA-MB-231; cells; INHIBITORS; KINASE;

D O I：

10.1016/j.ejmech.2023.115797

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Triple negative breast cancer (TNBC) is considered to be the most difficult subtype of breast cancer to treat because of its extremely prone to metastasis and the lack of targeted therapy drugs. New purine derivatives were synthesized and evaluated in a series of kinases and cell lines. The most active compounds 3g and 3j were selected based on their antiproliferative activities, then their pharmaceutical activity and mechanism in MDAMB-231 cells were analyzed. The results in vitro indicated that compounds 3g and 3j can induce MDA-MB-231 cells apoptosis, and inhibit its migration and angiogenesis through influencing protein expression such as Bcl-2, Bax, Bcl-xl, P38, MMP2, MMP9, AKT and EGFR. In vivo results indicate that compounds 3g and 3j can inhibit tumor growth and metastasis and reduce the expression of Ki67 and CD31 protein in TNBC xenograft models. These findings not only broaden our understanding of the anti-TNBC effects and mechanisms of compounds 3g and 3j, but also provide new ideas and reference directions for the treatment of TNBC.

引用

页数：9