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

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

Volume: 12 Issue: 5

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

Affiliation:

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

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.

Cite this article as:

Wu Jianrui, Peng Ting, Chen Fang, Leng Yixin, Tong Linjiang, Li Mengyuan, Qu Rong, Xie Hua, Ding Jian and Duan Wenhu, Synthesis and Anticancer Activity of 7,8-dihydroxy-4-arylcoumarins, Letters in Drug Design & Discovery 2015; 12 (5) . https://dx.doi.org/10.2174/1570180812666141111235026