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

Publication date: Available online 20 May 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Menghua Qu, Zhihao Liu, Dan Zhao, Changyuan Wang, Jianbin Zhang, Zeyao Tang, Kexin Liu, Xiaohong Shu, Hong Yuan, Xiaodong Ma
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 µM, 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 µM. Compound 7e may be selected as a potent FAK inhibitor for the treatment of pancreatic cancer.

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