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Chinese Journal of Organic Chemistry >

2019 , Vol. 39 >Issue 11: 3230 - 3236

DOI: https://doi.org/10.6023/cjoc201905013

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

  • Yuan Hu ,
  • Zhenyu Li ,
  • Yanjiao Ding ,
  • Zhiying Li ,
  • Zhiyong Liu ,
  • Yuemao Shen
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  • 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 date: 2019-05-08

  Online published: 2019-06-24

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)

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Abstract

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

Cite this article

Yuan Hu , Zhenyu Li , Yanjiao Ding , Zhiying Li , Zhiyong Liu , Yuemao Shen . Antitumor and Topoisomerase Ⅱα Inhibitory Activities of 3-Aryl-7-hydroxyquinolines[J]. Chinese Journal of Organic Chemistry, 2019 , 39(11) : 3230 -3236 . DOI: 10.6023/cjoc201905013

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