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

doi:10.6023/cjoc201806015

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

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6-取代芳基-2-甲氧基喹啉类拓扑异构酶Ⅱα抑制剂的合成及抗肿瘤活性研究

李志颖^a, 丁艳娇^b, 卜华港^a, 沈月毛^a

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 E-mail:yshen@sdu.edu.cn
基金资助:
国家重点基础研究发展计划（973计划，No.2010CB833802）、国家自然科学基金（Nos.81373304，81502921，91313303）、长江学者和创新团队发展计划（No.IRT13028）和国家杰出青年科学基金（No.30325044）资助项目.

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

Li Zhiying^a, Ding Yanjiao^b, Bu Huagang^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

Received:2018-06-12 Revised:2018-08-05 Published:2018-09-05
Contact: 10.6023/cjoc201806015 E-mail:yshen@sdu.edu.cn
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).

1. Antitumor and DNA Topoisomerase Ⅱα Inhibitory Activity of 6-Substituted-aryl-2-methoxyquinolines.PDF(1405KB)

Abstract

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

Cite this article

Li Zhiying, Ding Yanjiao, Bu Huagang, Shen Yuemao. Antitumor and DNA Topoisomerase Ⅱα Inhibitory Activity of 6-Substituted-aryl-2-methoxyquinolines[J]. Chin. J. Org. Chem., 2018, 38(12): 3204-3210.

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6-取代芳基-2-甲氧基喹啉类拓扑异构酶Ⅱα抑制剂的合成及抗肿瘤活性研究

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

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