Discovery of novel quinazoline derivatives bearing semicarbazone moiety as potent EGFR kinase inhibitors.

ABSTRACT: Aimed at discovering effective EGFR inhibitors, six series of quinazoline derivatives bearing a semicarbazone moiety were designed, synthesized and evaluated in different cancer cell lines (A549, HepG2, MCF-7 and PC-3). Most of the selected compounds showed remarkable cytotoxicity with IC₅₀ values reaching the nanomole range. Further, the inhibition efficacy of 11 compounds against EGFR kinases was tested, which demonstrated excellent IC₅₀ values in nanomolar level. Importantly, 2 compounds exhibited IC₅₀ values of 0.05 nM and 0.1 nM against wild type EGFR respectively, suggesting more potent activities than that of the positive control, Afatinib (4.0 nM). Excitingly, 2 compounds showed excellent enzyme inhibitory activity with 8.6 nM and 5.6 nM for double

SUBMITTER: Tu Y 

PROVIDER: S-EPMC6232652 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature