Synthesis and antitumor activities of novel coumarin derivatives containing chalcone moiety

To explore novel coumarin derivatives with more potent antitumor activity, a series of novel compounds were designed and synthesized by linking chalcone to coumarin′s framework. Starting from acetophenone and 4-methylbenzaldehyde, the target compounds were prepared through a reaction cascade, including Claisen-Schmidt, bromination, cyclization and elimination reactions affording twenty-four novel compounds whose structures were confirmed by ¹H NMR and ESI-MS techniques. In vitro antitumor activities of the compounds were evaluated against HepG2, DU145 and A549 cell lines by the standard MTT assay. The results showed that some of the target compounds exhibited strong anti-proliferative activities against selected tumor cells. Compounds Ⅰc, Ⅱb, Ⅱc and Ⅱd showed excellent anti-proliferative activities against HepG2 and A549 cell lines with the IC₅₀ values of 2. 05-9. 16 mol/L and 3. 48-10. 81 mol/L, respectively. The structure-activity relationship of novel coumarin derivatives containing chalcone moiety is also discussed.