Antimalarial histone deacetylase inhibitors containing cinnamate or NSAID components

Wheatley, Nicole C., Andrews, Katherine T., Tran, Truc L., Lucke, Andrew J., Reid, Robert C. and Fairlie, David P. (2010) Antimalarial histone deacetylase inhibitors containing cinnamate or NSAID components. Bioorganic & Medicinal Chemistry Letters, 20 23: 7080-7084. doi:10.1016/j.bmcl.2010.09.096

Author Wheatley, Nicole C.
Andrews, Katherine T.
Tran, Truc L.
Lucke, Andrew J.
Reid, Robert C.
Fairlie, David P.
Title Antimalarial histone deacetylase inhibitors containing cinnamate or NSAID components
Journal name Bioorganic & Medicinal Chemistry Letters   Check publisher's open access policy
ISSN 0960-894X
Publication date 2010-12-01
Sub-type Article (original research)
DOI 10.1016/j.bmcl.2010.09.096
Volume 20
Issue 23
Start page 7080
End page 7084
Total pages 5
Place of publication Oxford
Publisher Pergamon Press/Elsevier
Language eng
Formatted abstract
Malaria is the most lethal parasite-mediated tropical infectious disease, killing 1-2 million people each year. An emerging drug target is the enzyme Plasmodium falciparum histone deacetylase 1 (PfHDAC1). We report 26 compounds designed to bind the zinc and exterior surface around the entrance to the active site of PfHDAC1, 16 displaying potent in vitro antimalarial activity (IC 50 <100 nM) against P. falciparum. Selected compounds were shown to cause hyperacetylation of P. falciparum histones and be >10-fold more cytotoxic towards P. falciparum than a normal human cell type (NFF). Twenty-two inhibitors feature cinnamic acid derivatives or non-steroidal anti-inflammatory drugs (NSAIDs) as HDAC-binding components. A homology model of PfHDAC1 enzyme gives new insights to interactions likely made by some of these inhibitors. Results support PfHDAC1 as a promising new antimalarial drug target. © 2010 Elsevier Ltd. All rights reserved
Keyword HDAC inhibitor
Plasmodium falciparum
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2011 Collection
Institute for Molecular Bioscience - Publications
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Citation counts: TR Web of Science Citation Count  Cited 25 times in Thomson Reuters Web of Science Article | Citations
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Created: Sun, 21 Nov 2010, 10:06:49 EST