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7209913 
Journal Article 
Novel quinoline-3-carboxamides (Part 2): Design, optimization and synthesis of quinoline based scaffold as EGFR inhibitors with potent anticancer activity 
Aly, RM; Serya, RAT; El-Motwally, AM; Esmat, A; Abbas, S; Abou El Ella, DA; , 
2017 
Yes 
Bioorganic Chemistry
ISSN: 0045-2068
EISSN: 1090-2120 
ACADEMIC PRESS INC ELSEVIER SCIENCE 
SAN DIEGO 
368-392 
29096097 
WOS:000417682200036 
EGFR has a key role in cell growth. Its mutation and overexpression share in epithelial malignancies and tumor growth. Quinazoline and quinoline derivatives are common anticancer intracellular inhibitors of EGFR kinase, and their optimization is an important issue for development of potent targeted anticancer agents. Based on these facts, different strategies were used for optimizing our reported quinoline-3-carboxamide compound III (EGFR IC50 = 5.283 mM and MCF-7 IC50 = 3.46 mM) through different molecular modeling techniques. The optimized compounds were synthesized and subjected to EGFR binding assay and accordingly some more potent inhibitors were obtained. The most potent quinoline-3-carboxamides were the furan derivative 5o; thiophene derivative 6b; and benzyloxy derivative 10 showing EGFR IC50 values 2.61, 0.49 and 1.73 mu M, respectively. Furthermore, the anticancer activity of compounds eliciting potent EGFR inhibition (5o, 5p, 6b, 8a, 8b, and 10) was evaluated against MCF-7 cell line where they exhibited IC50 values 3.355, 3.647, 5.069, 3.617, 0.839 and 10.85 mu M, respectively. Compound 6b was selected as lead structure for further optimization hoping to produce more potent EGFR inhibitors. (C) 2017 Elsevier Inc. All rights reserved.