A hybrid of thiazolidinone with the hydroxamate scaffold for developing novel histone deacetylase inhibitors with antitumor activities

作者：Yang, Feifei; Peng, Shihong; Li, Yunqi; Su, Liqiang; Peng, Yangrui; Wu, Jing; Chen, Huang; Liu, Mingyao; Yi, Zhengfang^*; Chen, Yihua^*

来源：Organic and Biomolecular Chemistry, 2016, 14(5): 1727-1735.

DOI：10.1039/c5ob02250a

• CANCER-THERAPY
• TUMOR-METASTASIS
• MOLECULAR-MECHANISMS
• COLONY FORMATION
• HDAC INHIBITORS
• DESIGN
• ACETYLATION
• OPTIMIZATION
• PERSPECTIVES
• DERIVATIVES

A series of novel histone deacetylase (HDAC) inhibitors were designed, synthesized and evaluated based on the strategies of a hybrid of the classic pharmacophore of HDAC inhibitors with the thiazolidinone scaffold. Some of the compounds showed potent HDAC1 inhibition with nM IC50 values, more importantly, compound 12i displayed much better anti-metastatic effects than vorinostat (SAHA) against migration of the A549 cell line. Further mechanism exploration implied that compound 12i may inhibit tumor metastasis via modulating the epithelial-mesenchymal transition (EMT) and upregulating the acetylation of alpha-tubulin.

• 单位
  济南大学; 华东师范大学