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

被引：18

作者：

Yang, Feifei ^{[1
,2
,3
]}

Peng, Shihong ^{[1
,2
]}

Li, Yunqi ^{[1
,2
]}

Su, Liqiang ^{[1
,2
]}

Peng, Yangrui ^{[1
,2
]}

Wu, Jing ^{[1
,2
]}

Chen, Huang ^{[1
,2
]}

Liu, Mingyao ^{[1
,2
]}

Yi, Zhengfang ^{[1
,2
]}

Chen, Yihua ^{[1
,2
]}

机构：

[1] E China Normal Univ, Inst Biomed Sci, Shanghai Key Lab Regulatory Biol, Shanghai 200241, Peoples R China

[2] E China Normal Univ, Sch Life Sci, Shanghai 200241, Peoples R China

[3] Univ Jinan, Sch Biol Sci & Technol, Jinan 250022, Shandong, Peoples R China

来源：

ORGANIC & BIOMOLECULAR CHEMISTRY | 2016年 / 14卷 / 05期

基金：

中国国家自然科学基金; 高等学校博士学科点专项科研基金;

关键词：

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

D O I：

10.1039/c5ob02250a

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

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.

引用

收藏

页码：1727 / 1735

页数：9

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