New Chalcone‐Zerumbone Hybrids: Synthesis, In Vitro Anticancer Activity and Molecular Docking Study

ABSTRACT Chalcones and zerumbone share a common structural feature: an α,β ‐unsaturated ketone group, which is recognized as the key determinant of their anticancer activity. For the purpose of combining their promising anticancer property, eight new chalcone‐zerumbone hybrids were successfully designed and prepared via a convenient O ‐alkylation reaction between 4ʹ‐hydroxychalcones and 7‐bromozerumbone in DMF using K 2 CO 3 as a catalyst at room temperature for 18 h. As expected, all obtained chalcone hybrids with zerumbone exhibited significantly more potent cytotoxicity than their precursors, zerumbone and 4ʹ‐hydroxychalcones, against two human cancer cell lines, Hep‐G2 and MCF‐7, with IC 50 values ranging from 1.58 to 9.27 µM. Among eight prepared hybrids, 15e has the strongest activity against Hep‐G2 and MCF‐7 cell lines with IC 50 values of 1.68 and 1.58 µM, respectively. Notably, hybrids 15b, 15c, 15g , and 15 h showed good selectivity against tested cancer cell lines, with IC 50 values in normal Vero cells approximately 2–5‐fold higher than those in cancer cells. Molecular docking results also supported the findings from the experimental data.