A cyclodextrin-capped histone deacetylase inhibitor

被引：6

作者：

Amin, Jahangir ^{[1
]}

Puglisi, Antonino ^{[1
,2
]}

Clarke, James ^{[2
]}

Milton, John ^{[2
]}

Wang, Minghua ^{[3
]}

Paranal, Ronald M. ^{[4
]}

Bradner, James E. ^{[4
]}

Spencer, John ^{[1
]}

机构：

[1] Univ Sussex, Sch Life Sci, Dept Chem, Brighton BN1 9QJ, E Sussex, England

[2] Oxford Nanopore Technol Ltd, Oxford OX4 4GA, England

[3] Univ Toronto, Terrence Donnelly Ctr Cellular & Biomol Res, Toronto, ON M5S 3E1, Canada

[4] Dana Farber Canc Inst, Boston, MA 02115 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2013年 / 23卷 / 11期

关键词：

HDAC Inhibitors; Cyclodextrin conjugates; Molecular modelling; Cancer; ACID;

D O I：

10.1016/j.bmcl.2013.03.084

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

We have synthesized a beta-cyclodextrin (beta CD)-capped histone deacetylase (HDAC) inhibitor 3 containing an alkyl linker and a zinc-binding hydroxamic acid motif. Biological evaluation (HDAC inhibition studies) of 3 enabled us to establish the effect of replacing an aryl cap (in SAHA (vorinostat,)) 1 by a large saccharidic scaffold "cap''. HDAC inhibition was observed for 3, to a lesser extent than SAHA, and rationalized by molecular docking into the active site of HDAC8. However, compound 3 displayed no cellular activity. (C) 2013 Elsevier Ltd. All rights reserved.

引用

页码：3346 / 3348

页数：3

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