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

作　　者：LI Hong-Xia QIAN Yu-Mei XU Li-Sheng 李红侠;钱玉梅;徐礼生(School of Life and Food Engineering,Suzhou University,Suzhou 234000,China)

机构地区：[1]School of Life and Food Engineering,Suzhou University,Suzhou 234000,China

出　　处：《Chinese Journal of Structural Chemistry》2021年第7期933-941,841,共10页结构化学（英文）

基　　金：the Suzhou University Natural Science Key Project(No.2017yzd11,2020ykf23,2020ykf24);National Engineering Laboratory Open Fund Project(NEL-SCRT 002);Natural Science Foundation of An Hui Province(No.1908085MC100,KJ2020A0729,KJ2020A0737)。

摘　　要：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.

关 键 词：hydroxyquinazoline EFGR antitumor activity TOXICITY APOPTOSIS 

分 类 号：TQ460.1[化学工程—制药化工]