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Novel 4-anilinoquinazoline derivatives featuring an 1-adamantyl moiety as potent EGFR inhibitors with enhanced activity against NSCLC cell lines.

Abstract：

:With the aim of overcoming gefitinib resistance, a series of novel quinazoline derivatives bearing an adamantyl group on the aniline ring were synthesized as potent epidermal growth factor receptor (EGFR) inhibitors. Most of these analogues are comparable to gefitinib in their ability to inhibit non-small cell lung cancer (NSCLC) cell lines, and several also exhibited significantly enhanced anti-tumor potency. Specifically, compound 3d, with an IC50 value of 2.06 μM against A431 cells with the wild-type EGFR and of 0.009 μM against the gefitinib-sensitive cells, displayed approximately 5-fold higher potency than the lead compound to inhibit the cells harboring the EGFR(T790M) mutant. In addition, the molecular simulation and Western blot analysis results also indicated that these compounds effectively interfered with the EGFR(T790M) activity, and may serve as a new alternative structure to develop more effective antitumor agents.

journal_name

Eur J Med Chem

journal_title

European journal of medicinal chemistry

authors

Yu H,Li Y,Ge Y,Song Z,Wang C,Huang S,Jin Y,Han X,Zhen Y,Liu K,Zhou Y,Ma X

doi

10.1016/j.ejmech.2016.01.045

subject

Has Abstract

pub_date

2016-03-03 00:00:00

pages

195-203

eissn

0223-5234

issn

1768-3254

pii

S0223-5234(16)30043-5

journal_volume

110

pub_type

杂志文章

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