Discovery of Novel 2,4-Dianilinopyrimidine Derivatives Containing 4-(Morpholinomethyl)phenyl and N-Substituted Benzamides as Potential FAK Inhibitors and Anticancer Agents |
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| Authors: | Chun Han Kemin Shen Shijun Wang Zhijun Wang Feng Su Xi Wu Xiaoqin Hu Mengyao Li Jing Han Lintao Wu |
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| Institution: | 1.Department of Chemistry, Changzhi University, Changzhi 046011, China; (C.H.); (S.W.); (Z.W.); (F.S.); (X.W.); (X.H.); (M.L.);2.Department of Public Health and Preventive Medicine, Changzhi Medical College, Changzhi 046011, China;3.School of Chemistry and Materials Science, Jiangsu Normal University, Xuzhou 221116, China |
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| Abstract: | Focal adhesion kinase (FAK) is responsible for the development and progression of various malignancies. With the aim to explore novel FAK inhibitors as anticancer agents, a series of 2,4-dianilinopyrimidine derivatives 8a–8i and 9a–9g containing 4-(morpholinomethyl)phenyl and N-substituted benzamides have been designed and synthesized. Among them, compound 8a displayed potent anti-FAK activity (IC50 = 0.047 ± 0.006 μM) and selective antiproliferative effects against H1975 (IC50 = 0.044 ± 0.011 μM) and A431 cells (IC50 = 0.119 ± 0.036 μM). Furthermore, compound 8a also induced apoptosis in a dose-dependent manner, arresting the cells in S/G2 phase and inhibiting the migration of H1975 cells, all of which were superior to those of TAE226. The docking analysis of compound 8a was performed to elucidate its possible binding modes with FAK. These results established 8a as our lead compound to be further investigated as a potential FAK inhibitor and anticancer agent. |
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| Keywords: | FAK inhibitor 2 4-dianilinopyrimidine 4-(morpholinomethyl)phenyl N-substituted benzamides anticancer molecular docking |
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