Synthesis and Anticancer Activity of 7,8-dihydroxy-4-arylcoumarins

Author(s): Jianrui Wu, Ting Peng, Fang Chen, Yixin Leng, Linjiang Tong, Mengyuan Li, Rong Qu, Hua Xie, Jian Ding, Wenhu Duan

Journal Name: Letters in Drug Design & Discovery

Volume 12 , Issue 5 , 2015

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Graphical Abstract:


A series of 7,8-dihydroxy-4-arylcoumarins, the derivatives related to DW532 that was an anti-tumor agent targeting both kinase and tubulin, was prepared by Suzuki coupling reaction. Among them, compounds 6a, 6b, and 6c were found to exhibit anti-proliferation activities against human breast carcinoma MDA-MB-468 cells with IC50 values of 0.64, 0.69, and 1.33 μM, respectively and human epidermoid carcinoma A431 cells with IC50 values of 2.56, 1.78, and 2.29 μM, respectively. Further evaluation of the selected molecules revealed that they displayed broad-spectrum inhibitory activities against a panel of kinases including Flt-1, VEGFR2, RET, EGFR, etc. In vitro tubulin polymerization assay and molecular docking indicated that the substitution of 3’-OH and 4’-OCH3 on the 4-phenyl ring was essential to achieve potent tubulin inhibition.

Keywords: Anticancer, 4-Arylcoumarin, Cytotoxicity, Structure-activity relationship, Tubulin, Tyrosine kinase inhibition.

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Article Details

Year: 2015
Page: [366 - 373]
Pages: 8
DOI: 10.2174/1570180812666141111235026
Price: $65

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