Design, synthesis and biological evaluation of sulfonamide-substituted diphenylpyrimidine derivatives (Sul-DPPYs) as potent focal adhesion kinase (FAK) inhibitors with antitumor activity

被引：31

作者：

Qu, Menghua ^{[1
]}

Liu, Zhihao ^{[1
]}

Zhao, Dan ^{[1
]}

Wang, Changyuan ^{[1
]}

Zhang, Jianbin ^{[1
]}

Tang, Zeyao ^{[1
]}

Liu, Kexin ^{[1
]}

Shu, Xiaohong ^{[1
]}

Yuan, Hong ^{[2
]}

Ma, Xiaodong ^{[1
]}

机构：

[1] Dalian Med Univ, Coll Pharm, Dalian 116044, Peoples R China

[2] Dalian Med Univ, Affiliated Hosp 1, Clin Lab, Dalian 116011, Peoples R China

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2017年 / 25卷 / 15期

基金：

中国国家自然科学基金;

关键词：

Cancer; FAK; Inhibitor; Pyrimidine; Sulfonamide; IN-VIVO; CANCER; DISCOVERY; CELLS; ASSAY;

D O I：

10.1016/j.bmc.2017.05.044

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：

A class of sulfonamide-substituted diphenylpyrimidines (Sul-DPPYs) were synthesized to improve activity against the focal adhesion kinase (FAK). Most of these new Sul-DPPYs displayed moderate activity against the FAK enzyme with IC50 values of less than 100 nM; regardless, they could effectively inhibit several classes of refractory cancer cell lines with IC50 values of less than 10 mu M, including the pancreatic cancer cell lines (AsPC-1, Panc-1 and BxPC-3), the NSCLC-resistant H1975 cell line, and the B lymphocyte cell line (Ramos cells). Results of flow cytometry indicated that inhibitor 7e promoted apoptosis of pancreatic cancer cells in a dose-dependent manner. In addition, it almost completely induced the apoptosis at a concentration of 10 mu M. Compound 7e may be selected as a potent FAK inhibitor for the treatment of pancreatic cancer. (C) 2017 Elsevier Ltd. All rights reserved.

引用

页码：3989 / 3996

页数：8