Design, synthesis, docking studies and biological evaluation of novel chalcone derivatives as potential histone deacetylase inhibitors

[Display omitted] •Chalcone derivatives comprising hydroxamic acids or 2-aminobenzamide as zinc binding groups.•Anti-proliferative activity against human HepG2, MCF-7 and HCT-116 cell lines.•In vitro HDAIs activity.•Molecular docking to HDAC enzyme. A group of novel chalcone derivatives comprising hydroxamic acid or 2-aminobenzamide group as zinc binding groups (ZBG) were synthesized. The structure of the prepared compounds was fully characterized by IR, NMR and elemental microanalyses. Most of the tested compounds displayed strong to moderate HDAC inhibitory activity. Some of these compounds showed potent anti-proliferative activity against human HepG2, MCF-7 and HCT-116 cell lines. In particular, compounds 4a and 4b exhibited significant anti-proliferative activity against the three cell lines compared to SAHA as reference drug and displayed promising profile as anti-tumor candidates. The results indicated that these chalcone derivatives could serve as a promising lead compounds for further optimization as antitumor agents.