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 fac...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.展开更多
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)。
文摘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.
