Design, synthesis, antiproliferative activity and docking studies of quinazoline derivatives bearing 2,3-dihydro-indole or 1,2,3,4-tetrahydroquinoline as potential EGFR inhibitors

被引：23

作者：

OuYang, Yiqiang ^{[1
]}

Zou, Wensheng ^{[1
]}

Peng, Liang ^{[1
]}

Yang, Zunhua ^{[2
]}

Tang, Qidong ^{[1
]}

Chen, Mengzi ^{[1
]}

Jia, Shuang ^{[1
]}

Zhang, Hong ^{[1
]}

Lan, Zhou ^{[1
]}

Zheng, Pengwu ^{[1
]}

Zhu, Wufu ^{[1
]}

机构：

[1] Jiangxi Sci & Technol Normal Univ, Sch Pharm, Jiangxi Prov Key Lab Drug Design & Evaluat, Nanchang 330013, Jiangxi, Peoples R China

[2] Jiangxi Univ Tradit Chinese Med, Coll Pharm, Nanchang 330004, Jiangxi, Peoples R China

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2018年 / 154卷

关键词：

Quinazoline derivatives; Synthesis; Antiproliferative activity; EGFR inhibitors; GROWTH-FACTOR RECEPTOR; CANCER-CELLS; LUNG ADENOCARCINOMA; COMBINATION; RESISTANCE; MUTATIONS; GEFITINIB; AFATINIB; DEATH;

D O I：

10.1016/j.ejmech.2018.05.006

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Eight series of quinazoline derivatives bearing 2,3-dihydro-indole or 1,2,3,4-tetrahydroquinoline were designed, synthesized and evaluated for the IC50 values against three cancer cell lines (A549, MCF-7 and PC-3). Most of the forty nine target compounds showed excellent antiproliferative activity against one or several cancer cell lines. The compound 13a showed the best activity against A549, MCF-7 and PC-3 cancer cell lines, with the IC50 values of 1.09 +/- 0.04 mu M, 1.34 +/- 0.13 M and 1.23 +/- 0.09 M, respectively. Eight selected compounds were further selected to evaluated for the inhibitory activity against EGFR kinase. Three of them showed equal activity against EGFR kinase to positive control afatinib. AnnexinV-FITC, propidium iodide (PI) double staining and acridine orange single staining results indicated that the compound 13a could induce apoptosis of human lung cancer A549 cells. (C) 2018 Elsevier Masson SAS. All rights reserved.

引用

页码：29 / 43

页数：15

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