Design, Synthesis, and Biological Activity of Hydroxamic Tertiary Amines as Histone Deacetylase Inhibitors

被引：8

作者：

Terracciano, Stefania ^{[1
]}

Chini, Maria Giovanna ^{[1
]}

Riccio, Raffaele ^{[1
]}

Bruno, Ines ^{[1
]}

Bifulco, Giuseppe ^{[1
]}

机构：

[1] Univ Salerno, Dipartimento Sci Farmaceut & Biomed, I-84084 Fisciano, SA, Italy

来源：

CHEMMEDCHEM | 2012年 / 7卷 / 04期

关键词：

docking; fluorimetric assays; inhibitors; histone deacetylase; hydroxamic tertiary amines; TRANS-RETINOIC ACID; REDUCTIVE ALKYLATION; EPIGENETIC THERAPY; MOLECULAR DOCKING; HDAC INHIBITORS; CLINICAL-TRIAL; VALPROIC ACID; PHASE-II; CANCER; DEPSIPEPTIDE;

D O I：

10.1002/cmdc.201100531

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Herein we describe the design, synthesis, and biological evaluation of new hydroxamic tertiary amines as histone deacetylase (HDAC) inhibitors. These compounds have allowed us to clarify the influence of cap group dimension and hydrophobicity on HDAC inhibitory activity. This report also reveals the recognition pattern between the linear compounds and the histone deacetylase-like protein (HDLP) model receptor, and discusses the synthesis and in vitro evaluation of HDAC inhibitory activity in HeLa cell nuclear extracts. We obtained good qualitative agreement between experimental results and theoretical predictions, confirming that appropriately substituted hydroxamic tertiary amines are potential active HDAC inhibitors.

引用

页码：694 / 702

页数：9

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