期刊
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
卷 155, 期 -, 页码 782-796出版社
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2018.06.024
关键词
Anilinoquinazolines; ERK; EGFR; Synthesis; Docking
资金
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ain Shams University, Egypt
- Pharmaceutical Chemistry Department, Faculty of Pharmacy, Cairo University, Egypt
- Deanship of Scientific Research and the Research Center, College of Pharmacy, King Saud University
Epidermal growth factor receptor (EGFR) signaling pathway has been previously investigated for its significant role in the progression of different types of malignant tumors, where development of small molecules targeting EGFR is well known strategy for design of antitumor agents. Herein, we report the design and synthesis of two series of 6-(2-substitutedacetamido)-4-anilinoquinazolines (6a-x and 13a-d) as EGFR inhibitors. All the newly synthesized quinazoline derivatives were in vitro evaluated for their anti-proliferative activity towards MCF-7 (Breast Cancer) and HepG2 (Hepatocellular carcinoma) cell lines. In particular, compound 6n showed significant inhibitory activity against MCF-7 and HepG2 cell lines (IC50=3 and 16 mu M, respectively), compared to that of Erlotinib (IC50 = 20 and 25 mu M, respectively). Western blotting of 6n at MCF-7 cell line revealed the dual inhibitory activity of 6n towards diminishing the phosphorylated levels for EGFR and ERK. Also, ELISA assay confirmed the anti-EGFR activity of compound 6n (IC50= 0.037 mu M). Finally, a molecular docking study showed the potential binding mode of 6n within the ATP catalytic binding site of EGFR, exhibiting similar binding mode to EGFR inhibitor Erlotinib. (C) 2018 Elsevier Masson SAS. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据