埃罗替尼
化学
表皮生长因子受体抑制剂
MAPK/ERK通路
表皮生长因子受体
IC50型
MCF-7型
喹唑啉
盐酸厄洛替尼
信号转导
癌症研究
对接(动物)
癌细胞
体外
磷酸化
细胞培养
药理学
表皮生长因子
癌症
受体
生物化学
立体化学
生物
内科学
医学
护理部
遗传学
人体乳房
作者
Rania S.M. Ismail,Sahar M. Abou‐Seri,Wagdy M. Eldehna,Nasser S. M. Ismail,Sara M. Elgazwi,Hazem A. Ghabbour,Mahmoud S. Ahmed,Fathi T. Halaweish,Dalal A. Abou El Ella
标识
DOI:10.1016/j.ejmech.2018.06.024
摘要
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 μM, respectively), compared to that of Erlotinib (IC50 = 20 and 25 μM, 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 μM). 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.
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