Chinese Journal of Organic Chemistry ›› 2019, Vol. 39 ›› Issue (11): 3230-3236.DOI: 10.6023/cjoc201905013 Previous Articles     Next Articles


胡园a, 李震宇b, 丁艳娇b, 李志颖a, 刘志勇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:2019-05-08 发布日期:2019-06-24
  • 通讯作者: 沈月毛
  • 基金资助:

Antitumor and Topoisomerase Ⅱα Inhibitory Activities of 3-Aryl-7-hydroxyquinolines

Hu Yuana, Li Zhenyub, Ding Yanjiaob, Li Zhiyinga, Liu Zhiyonga, 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:2019-05-08 Published:2019-06-24
  • Contact: Shen Yuemao
  • Supported by:
    the National Basic Research Program of China(973计划);the National Basic Research Program of China(2010CB833802);the National Natural Science Foundation of China(81273384);the National Natural Science Foundation of China(90913024);the National Natural Science Foundation of China(91313303);the National Science Foundation for Distinguished Young Scholars of China(30325044);the Program for Changjiang Scholars and Innovative Research Team in University(IRT_17R68)

Human deoxyribonucleic acid (DNA) topoisomerase Ⅱα (Topo Ⅱα) is one of the important therapeutic targets for the treatment of cancers. To further discover Topo Ⅱα inhibitors with high efficiency and low toxicity, twenty-one 3-aryl-7-hydroxyquinolines were designed and synthesized by scaffold hopping of the lead compound 4-(6-hydroxynaph-thalen-2-yl)benzene-1, 2-diol (CS1). These compounds were evaluated for their inhibitory activity against Topo Ⅱα activity in DNA relaxation assays, and evaluated for the antitumor activity in in vitro growth inhibition assays against human triple negative breast cancer MDA-MB-231 cells and human cervical cancer HeLa cells. DNA relaxation assays showed that most compounds have inhibitory activity against Topo Ⅱα. In vitro growth inhibition assays showed that 3-(2, 4-dimethoxyphenyl)-7-hydroxyquinoline (4j) has obvious cytotoxicity against HeLa cells (IC50=0.8 μmol·L-1), and 3-(4-hydroxyphenyl)-7-hydroxyquinoline (4e) has evident cytotoxicity against both MDA-MB-231 (IC50=1.1 μmol·L-1) and HeLa cell lines (IC50=4.2 μmol·L-1). These results provide insight into the development of novel quinoline topoisomerase Ⅱα inhibitors.

Key words: topoisomerase Ⅱα, design and synthesis, structure optimization, antitumor activity