Medicinal Chemistry

Honorary Life Fellow
Kings College
University of Cambridge


Synthesis of Aryl-Substituted Naphthalenoids as Potent Topoisomerase Inhibitors

Author(s): Yan Shen, Wang Chen, Zhenyu Li and Yuemao Shen

Affiliation: School of Pharmaceutical Sciences, Shandong University, No. 44 West Wenhua Road, Jinan, Shandong 250012, P.R. China.

Graphical Abstract:


Twelve new aryl-substituted naphthalenoids (1-7, 9, 10, and 13-16) together with four known ones (8, and 11- 13) have been designed and synthesized. Their antitumor activities were evaluated by sulforhodamine B assay on human breast cancer MDA-MB-231, human lung cancer A549 and human cervical cancer HeLa cell lines. Four compounds (2, 4, 10 and 12) showed potent inhibitory activities against the growth of the three cell lines with IC50 between 0.34-3.49 µM, and were more potent than the reference etoposide (IC50 3.67-13.78 µM). DNA relaxation assay revealed that compound 2 showed potent inhibitory activity against Topo IIα in vitro. The structure-activity relationships of these compounds were discussed, suggesting that further structural optimizations of aryl-substituted naphthalenoids could lead to the discovery of potent antitumor agents targeting topoisomerases.

Keywords: Topoisomerase I, topoisomerase IIα, aryl-substituted naphthalenoids, antitumor activity.

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Article Details

Page: [533 - 539]
Pages: 7
DOI: 10.2174/15734064113096660048
Price: $58