Towards histone deacetylase inhibitors as new antimalarial drugs

Andrews, Katherine T., Tran, Tran N. and Fairlie, David P. (2012) Towards histone deacetylase inhibitors as new antimalarial drugs. Current Pharmaceutical Design, 18 24: 3467-3479. doi:10.2174/138161212801327257

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Author Andrews, Katherine T.
Tran, Tran N.
Fairlie, David P.
Title Towards histone deacetylase inhibitors as new antimalarial drugs
Journal name Current Pharmaceutical Design   Check publisher's open access policy
ISSN 1381-6128
1873-4286
Publication date 2012-08
Sub-type Article (original research)
DOI 10.2174/138161212801327257
Volume 18
Issue 24
Start page 3467
End page 3479
Total pages 14
Place of publication Bussum, Netherlands
Publisher Bentham Science Publishers
Collection year 2013
Language eng
Abstract Histone deacetylases (HDACs) are important enzymes that effect post-translational modifications of proteins by altering the acetylation state of lysine residues. HDACs control epigenetic changes that trigger cell transformation and proliferation of transformed cells associated with many diseases. These enzymes are validated drug targets for some types of cancer and are promising therapeutic targets for a range of other diseases, including malaria. Annually, there are ∼500 million clinical cases of malaria and ∼0.8-1.2 million deaths. There is no licensed vaccine for preventing malaria, and parasites that cause malaria are becoming resistant to current drugs, necessitating the search for new therapies. HDAC inhibitors are emerging as a promising new class of antimalarial drugs with potent and selective action against Plasmodium parasites in vitro. Recent studies on the effects of HDAC inhibitors on the growth and development of P. falciparum have provided important new information on transcriptional regulation in malaria parasites and have validated the potential of this class of inhibitors for malaria therapy. To realise effective HDAC inhibitors for clinical trials, next generation inhibitors must not inhibit other human HDACs or proteins required for normal human physiology, be highly selective in killing parasites in vivo without killing normal host cells, and have improved bioavailability and pharmacokinetic profiles. This review summarizes current knowledge about malaria parasite HDACs and HDAC inhibitors with antimalarial properties, and provides insights for their development into new drugs for treatment of malaria.
Keyword Histone deacetylase
HDAC inhibitor
Malaria
Plasmodium falciparum
Antimalarial drugs
Post-translational modifications
Epigenetic changes
Vaccine
Bioavailability
Pharmacokinetic profiles
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
Institute for Molecular Bioscience - Publications
 
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Created: Wed, 08 Aug 2012, 10:55:37 EST by Susan Allen on behalf of Institute for Molecular Bioscience