Synthesis and Anticancer Activity of 7,8-dihydroxy-4-arylcoumarins
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
Keywords: Anticancer, 4-Arylcoumarin, Cytotoxicity, Structure-activity relationship, Tubulin, Tyrosine kinase inhibition.
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