School of Pharmaceutical Sciences, Guizhou University, Guiyang, China.
State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, China.
J Enzyme Inhib Med Chem. 2022 Dec;37(1):832-843. doi: 10.1080/14756366.2022.2046567.
This paper described our efforts to develop dianilinopyrimidines as novel EGFR inhibitors. All the target compounds were tested for inhibitory effects against wild type EGFR (EGFR) and three tumour cells, including A549, PC-3, and HepG2. Some of the compounds performed well in antitumor activities. Especially, compound 2-((2-((4-(3-fluorobenzamido)phenyl)amino)-5-(trifluoromethyl) pyrimidin-4-yl)amino)--methylthiophene-3-carboxamide showed higher anti-tumour activities than Gefitinib. The IC values of compound against A549, PC-3, and HepG2. reached 0.56 μM, 2.46 μM, and 2.21 μM, respectively. In addition, further studies indicated that compound could induce apoptosis against A549 cells and arrest A549 cells in the G2/M phase. Molecular docking studies showed that compound could closely interact with EGFR. Generally, compound was the potential for developing into an anti-tumour drug.
本文介绍了我们开发二苯胺嘧啶作为新型 EGFR 抑制剂的努力。所有目标化合物均测试了对野生型 EGFR(EGFR)和三种肿瘤细胞(包括 A549、PC-3 和 HepG2)的抑制作用。一些化合物在抗肿瘤活性方面表现良好。特别是,化合物 2-((2-((4-(3-氟苯甲酰胺基)苯基)氨基)-5-(三氟甲基)嘧啶-4-基)氨基)-甲基噻吩-3-甲酰胺对肿瘤的抑制活性高于吉非替尼。化合物对 A549、PC-3 和 HepG2 的 IC 值分别达到 0.56 μM、2.46 μM 和 2.21 μM。此外,进一步的研究表明,化合物可以诱导 A549 细胞凋亡,并将 A549 细胞阻滞在 G2/M 期。分子对接研究表明,化合物可以与 EGFR 紧密相互作用。总的来说,化合物具有开发成抗肿瘤药物的潜力。