@article{b52d59de790c4280a424bef07bf0de16,
title = "Novel series of 6-(2-substitutedacetamido)-4-anilinoquinazolines as EGFR-ERK signal transduction inhibitors in MCF-7 breast cancer cells",
abstract = "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.",
keywords = "Anilinoquinazolines, Docking, EGFR, ERK, Synthesis",
author = "Ismail, {Rania S.M.} and Abou-Seri, {Sahar M.} and Eldehna, {Wagdy M.} and Ismail, {Nasser S.M.} and Elgazwi, {Sara M.} and Ghabbour, {Hazem A.} and Ahmed, {Mahmoud Salama} and Halaweish, {Fathi T.} and {Abou El Ella}, {Dalal A.}",
note = "Funding Information: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ain Shams University, Egypt, is highly appreciated for supporting this research. Pharmaceutical Chemistry Department, Faculty of Pharmacy, Cairo University, Egypt, is highly appreciated for funding this research work, and for HRMS analyses, the authors would like to extend their sincere appreciation to the Deanship of Scientific Research and the Research Center, College of Pharmacy, King Saud University for their funding of this research. The authors would like to acknowledge OpenEye molecular modeling software for supporting an academic license. Funding Information: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ain Shams University, Egypt, is highly appreciated for supporting this research. Pharmaceutical Chemistry Department, Faculty of Pharmacy, Cairo University , Egypt, is highly appreciated for funding this research work, and for HRMS analyses, the authors would like to extend their sincere appreciation to the Deanship of Scientific Research and the Research Center, College of Pharmacy, King Saud University for their funding of this research. The authors would like to acknowledge OpenEye molecular modeling software for supporting an academic license. Publisher Copyright: {\textcopyright} 2018 Elsevier Masson SAS",
year = "2018",
month = jul,
day = "15",
doi = "10.1016/j.ejmech.2018.06.024",
language = "English (US)",
volume = "155",
pages = "782--796",
journal = "European Journal of Medicinal Chemistry",
issn = "0223-5234",
publisher = "Elsevier Masson SAS",
}