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

作者：Yang, Feifei; Shan, Peipei; Zhao, Na; Ge, Di; Zhu, Kongkai; Jiang, Cheng-shi; Li, Peifeng^*; Zhang, Hua^*

来源：Bioorganic & Medicinal Chemistry Letters, 2019, 29(1): 15-21.

DOI：10.1016/j.bmcl.2018.11.027

• 1,2,4-Oxadiazole
• Hydroxamate
• HDAC inhibitors
• Structure-activity relationships
• Antitumor

Histone deacetylases (HDACs) has proved to be promising target for the development of antitumor drugs. In this study, we reported the design and synthesis of a class of novel hydroxamate-based bis-substituted aromatic amide HDAC inhibitors with 1,2,4-oxadiazole core. Most newly synthesized compounds displayed excellent HDAC1 inhibitory effects and significant anti-proliferative activities. Among them, compounds 11a and 11c increased acetylation of histone H3 and H4 in dose-dependent manner. Furthermore, 11a and 11c remarkably induced apoptosis in HepG2 cancer cells. Finally, the high potency of compound 11a was rationalized by molecular docking studies.

• 出版日期2019-1-1
• 单位济南大学; 青岛大学