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

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

  • Bioorg Med Chem. 2017 Aug 1;25(15):3989-3996. doi: 10.1016/j.bmc.2017.05.044.
Menghua Qu 1,  Zhihao Liu 1,  Dan Zhao 1,  Changyuan Wang 1,  Jianbin Zhang 1,  Zeyao Tang 1,  Kexin Liu 1,  Xiaohong Shu 2,  Hong Yuan 3,  Xiaodong Ma 4
Affiliations

Affiliations

  • 1 College of Pharmacy, Dalian Medical University, Dalian 116044, PR China.
  • 2 College of Pharmacy, Dalian Medical University, Dalian 116044, PR China. Electronic address: xiaohong_shu@dlmedu.edu.cn.
  • 3 Clinical Laboratory, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, PR China. Electronic address: yuanhonglab@163.com.
  • 4 College of Pharmacy, Dalian Medical University, Dalian 116044, PR China. Electronic address: xiaodong.ma@139.com.
PMID: 28576633 DOI: 10.1016/j.bmc.2017.05.044
Abstract

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 100nM; regardless, they could effectively inhibit several classes of refractory Cancer cell lines with IC50 values of less than 10µM, 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 10µM. Compound 7e may be selected as a potent FAK Inhibitor for the treatment of pancreatic Cancer.

Keywords

Cancer; FAK; Inhibitor; Pyrimidine; Sulfonamide.

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