Development of hydroxamate-based histone deacetylase inhibitors containing 1,2,4-oxadiazole moiety core with antitumor activities.

•Thirteen new hydroxamate-based bis-substituted aromatic amide HDAC inhibitors with 1,2,4-oxadiazole core were obtained.•The structures were elucidated by comprehensive spectroscopic analyses.•Three compounds displayed excellent HDAC1 inhibitory effects and significant anti-proliferative activities.•Two compounds increased acetylation of histone H3 and H4 in dose-dependent manner.•Two compounds remarkably induced apoptosis in HepG2 cancer cells.