Synthesis and structure-activity relationship of histone deacetylase (HDAC) inhibitors with triazole-linked cap group

被引：91

作者：

Chen, Po C. ^{[1
]}

Patil, Vishal ^{[1
]}

Guerrant, William ^{[1
]}

Green, Patience ^{[1
]}

Oyelere, Adegboyega K. ^{[1
]}

机构：

[1] Georgia Inst Technol, Sch Chem & Biochem, Parker H Petit Inst Bioengn & Biosci, Atlanta, GA 30332 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2008年 / 16卷 / 09期

基金：

美国国家科学基金会;

关键词：

histone deacetylase ( HDAC); histone deacetylase-like protein (HDLP); suberoylanilide hydroxamic acid ( SAHA); trichostatin A (TSA); zinc-binding group (ZBG); SAHA-like hydroxamates; 1,2,3-triazole; click chemistry; molecular docking; AutoDock;

D O I：

10.1016/j.bmc.2008.03.050

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Histone deacetylase (HDAC) inhibition is a recent, clinically validated therapeutic strategy for cancer treatment. Small molecule HDAC inhibitors identified so far fall in to three distinct structural motifs: the zinc-binding group (ZBG), a hydrophobic linker, and a recognition cap group. Here we report the suitability of a 1,2,3-triazole ring as a surface recognition cap group-linking moiety in suberoylanilide hydroxamic acid-like (SAHA-like) HDAC inhibitors. Using "click'' chemistry (Huisgen cycloaddition reaction), several triazole-linked SAHA-like hydroxamates were synthesized. Structure - activity relationship revealed that the position of the triazole moiety as well as the identity of the cap group markedly affected the in vitro HDAC inhibition and cell growth inhibitory activities of this class of compounds. Published by Elsevier Ltd.

引用

页码：4839 / 4853

页数：15

共 34 条

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