Design,Synthesis and Anticancer Activity Evaluation of Novel Quinazoline Derivatives as EFGR Inhibitors

Malignant tumor is one of the major diseases that seriously threaten human health today.Compared with traditional chemotherapy,targeted drug therapy has become a new idea of tumor therapy.And EGFR(epidermal growth factor receptor)is highly expressed in many human tumor cell lines,which is a biomarker of tumor proliferation.In this paper,small molecule tyrosine kinase inhibitors with quinazoline structure aiming at EGFR were studied.A series of novel quinazoline derivatives(4a~4l)have been designed and synthesized from 4-hydroxyquinazoline as the parent core.Structures of target compounds were characterized by 1H NMR and 13C NMR spectra.The in vitro anticancer activity of compounds 4a~4l was evaluated by MTT assay against Hela,MCF-7 and A549 tumor cell lines,and apoptosis-inducing capacity was investigated by Annexin-V/PI staining assay.The results showed that all compounds had good antitumor activity against the test tumor cell lines.Especially,compound 4a exhibited the best anticancer activity(IC_(50)=10.23μM)against Hela cell lines,remarkable ability to induce apoptosis,and low toxicity,which identified 4a as a promising anticancer drug aiming at EFGR.