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

• DOI: 10.1016/j.ejmech.2018.05.006
• Publication Date: 2018-05-10T00:37:55Z
• Authors: Yiqiang OuYang; Wensheng Zou; Liang Peng; Zunhua Yang; Qidong Tang; Mengzi Chen; Shuang Jia; Hong Zhang; Zhou Lan; Pengwu Zheng; Wufu Zhu
• Keywords: 0301 basic medicine; Indoles; Dose-Response Relationship, Drug; Molecular Structure; Antineoplastic Agents; Apoptosis; 3. Good health; ErbB Receptors; Molecular Docking Simulation; Structure-Activity Relationship; 03 medical and health sciences; Cell Line, Tumor; Drug Design; Quinazolines; Quinolines; Humans; Drug Screening Assays, Antitumor; Protein Kinase Inhibitors; Cell Proliferation

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 μM, 1.34 ± 0.13 μM and 1.23 ± 0.09 μM, 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.