Chin. J. Org. Chem. ›› 2018, Vol. 38 ›› Issue (12): 3204-3210.DOI: 10.6023/cjoc201806015 Previous Articles     Next Articles



李志颖a, 丁艳娇b, 卜华港a, 沈月毛a   

  1. a 山东大学药学院 天然产物化学教育部重点实验室 济南 250012;
    b 山东大学附属省立医院药剂科 济南 250021
  • 收稿日期:2018-06-12 修回日期:2018-08-05 发布日期:2018-09-05
  • 通讯作者: 沈月毛
  • 基金资助:


Antitumor and DNA Topoisomerase Ⅱα Inhibitory Activity of 6-Substituted-aryl-2-methoxyquinolines

Li Zhiyinga, Ding Yanjiaob, Bu Huaganga, Shen Yuemaoa   

  1. a Key Laboratory of Chemical Biology(Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Jinan 250012;
    b Department of Pharmacy, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021
  • Received:2018-06-12 Revised:2018-08-05 Published:2018-09-05
  • Contact: 10.6023/cjoc201806015
  • Supported by:

    Project supported by the National Basic Research Program of China (973 Program, No. 2010CB833802), the National Natural Science Foundation of China (Nos. 81373304, 81502921, 90913024) and the Distinguished Young Scholars Grant (No. 30325044).

Human DNA Topoisomerase Ⅱα (Topo Ⅱα) is one of the important therapeutic targets for the treatment of cancers. Our previous study showed that p-terphenyls have inhibitory effects on Topo Ⅱα and inhibit the proliferation of human breast ductal carcinoma cells. In this study, nineteen 6-substituted aryl-2-methoxyquinolines (3a~3s) were designed, synthesized and evaluated for their cytotoxicity against the growth of human triple negative breast cancer MDA-MB-231 cell line and inhibitory activity against Topo Ⅱα. Among these compounds, 6-(4-(hydroxymethyl)phenyl)-2-methoxyquinoline (3b) showed the most potent activity (IC50=9.9 μmol·L-1). These results have important significance for the further study of aryl quinoline TopoⅡα inhibitors.

Key words: Topoisomerase Ⅱα, Synthesis, Structure optimization, Antitumor activity