Citation: Hu Yuan, Li Zhenyu, Ding Yanjiao, Li Zhiying, Liu Zhiyong, Shen Yuemao. 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 shu

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

Hu Yuan ^a ,
Li Zhenyu ^b ,
Ding Yanjiao ^b ,
Li Zhiying ^a ,
Liu Zhiyong ^a ,
Shen Yuemao ^a,,

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

Corresponding author: Shen Yuemao, yshen@sdu.edu.cn
Received Date: 8 May 2019
Revised Date: 6 June 2019
Available Online: 24 November 2019
Fund Project: the National Basic Research Program of China 2010CB833802Project supported by the National Basic Research Program of China (973 Program, No. 2010CB833802), the National Natural Science Foundation of China (Nos. 81273384, 90913024, 91313303), the National Science Foundation for Distinguished Young Scholars of China (No. 30325044) and the Program for Changjiang Scholars and Innovative Research Team in University (No. IRT_17R68)the National Natural Science Foundation of China 81273384the National Natural Science Foundation of China 90913024the National Science Foundation for Distinguished Young Scholars of China 30325044the National Natural Science Foundation of China 91313303the National Basic Research Program of China 973 Programthe Program for Changjiang Scholars and Innovative Research Team in University IRT_17R68

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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.
- topoisomerase Ⅱα,
- design and synthesis,
- structure optimization,
- antitumor activity
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