Chinese Journal of Organic Chemistry ›› 2021, Vol. 41 ›› Issue (9): 3617-3624.DOI: 10.6023/cjoc202103059 Previous Articles     Next Articles

ARTICLES

新型喹啉-吲哚衍生物的设计、合成及抗肿瘤活性研究

王胜辉a, 关永风b, 刘秀娟c, 原信颖c, 蔚广曦a, 李银茹a, 张雁冰c, 宋健a,c,*(), 李雯b,c,*(), 张赛扬a,c,*()   

  1. a 郑州大学基础医学院 郑州 450001
    b 郑州大学化工学院 郑州 450001
    c 郑州大学药学院 郑州 450001
  • 收稿日期:2021-03-30 修回日期:2021-05-25 发布日期:2021-06-29
  • 通讯作者: 宋健, 李雯, 张赛扬
  • 作者简介:
    † 共同第一作者.
  • 基金资助:
    国家自然科学基金(81703541); 国家自然科学基金(81673322); 国家自然科学基金(U2004123); 中国博士后科学基金(2018M632812)

Design, Synthesis and Anticancer Activity Studies of Novel Quinoline-Indole Derivatives

Shenghui Wanga, Yongfeng Guanb, Xiujuan Liuc, Xinying Yuanc, Guangxi Yua, Yinru Lia, Yanbing Zhangc, Jian Songa,c(), Wen Lib,c(), Saiyang Zhanga,c()   

  1. a School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001
    b School of Chemical Engineering, Zhengzhou University, Zhengzhou 450001
    c School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001
  • Received:2021-03-30 Revised:2021-05-25 Published:2021-06-29
  • Contact: Jian Song, Wen Li, Saiyang Zhang
  • About author:
    † These authors contributed equally to this work.
  • Supported by:
    National Natural Science Foundation of China(81703541); National Natural Science Foundation of China(81673322); National Natural Science Foundation of China(U2004123); China Postdoctoral Science Foundation(2018M632812)

As the continuation of our studies on novel and effective anti-cancer agents, a series of novel quinoline-indole derivatives were firstly designed and synthesized by molecular hybridization strategy and Lewis acid‐catalyzed coupling reactions. Their antiproliferative potency on gastric cancer cell line MGC-803, colon cancer cell line HCT-116, and esophageal cancer cell line Kyse450 of all the targeted compounds was explored using methyl thiazolyl tetrazolium (MTT) assay. 2-Chloro-4-(5-methoxy-1H-indol-3-yl)quinoline (9b) exhibited potently inhibitory activity against MGC-803, HCT-116, and Kyse450 cells with IC50 values of 0.58, 0.68 and 0.59 µmol•L–1. Further mechanism studies suggested that compound 9b inhibited the cell colony formation of MGC-803 and HGC-27 cells. Compound 9b induced an intrinsic apoptosis and down- regulated the levels of apoptosis related proteins in MGC-803 and HGC-27 cells. Meanwhile, compound 9b arrested MGC-803 and HGC-27 cells at the G2/M phase. Taken together, these results indicated that compound 9b might be a valuable lead compound for anticancer agents.

Key words: quinoline, indole, anticancer activity, proliferation, apoptosis, cell cycle arrest