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Novel Quinazoline Derivatives Bearing Various 4‐Aniline Moieties as Potent EGFR Inhibitors with Enhanced Activity Against NSCLC Cell Lines
Author(s) -
Wang Changyan,
Sun Yajun,
Zhu Xingqi,
Wu Bin,
Wang Qiao,
Zhen Yuhong,
Shu Xiaohong,
Liu Kexin,
Zhou Youwen,
Ma Xiaodong
Publication year - 2016
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12692
Subject(s) - gefitinib , quinazoline , egfr inhibitors , epidermal growth factor receptor , ic50 , chemistry , pharmacology , in vitro , biochemistry , receptor , biology , stereochemistry
A class of novel quinazoline derivatives bearing various C ‐4 aniline moieties was synthesized and biologically evaluated as potent epidermal growth factor receptor ( EGFR ) inhibitors for intervention of non‐small‐cell lung cancer ( NSCLC ). Most of these inhibitors are comparable to gefitinib in inhibiting these cancer cell lines, and several of them even displayed superior inhibitory activity. In particular, analogue 5b with an IC 50 of 0.10 μ m against the EGFR wild‐type A431 cells and 5c with an IC 50 of 0.001 μ m against the gefitinib‐sensitive HCC 827 cells ( EGFR del E746‐A750) was identified as highly active EGFR inhibitors. It was also significant that the discovered analogue 2f , not only has high potency against the gefitinib‐sensitive cells ( IC 50 = 0.031 μ m ), but also possesses remarkably improved activity against the gefitinib‐resistant cells. In addition, the enzymatic assays and the Western blot analysis for evaluating the effects of the typical inhibitors indicated that these molecules strongly interfere with the EGFR target.