Charles Darwin University

CDU eSpace
Institutional Repository

 
CDU Staff and Student only
 

Ex vivo activity of histone deacetylase inhibitors against multidrug-resistant clinical isolates of Plasmodium falciparum and P. vivax

Marfurt, Jutta, Chalfein, Ferryanto, Prayoga, Pak, Wabiser, Frans, Kenangalem, Enny, Piera, Kim A., Fairlie, David, Tjitra, Emiliana, Anstey, Nicholas M., Andrews, Kathy and Price, Ric N. (2010). Ex vivo activity of histone deacetylase inhibitors against multidrug-resistant clinical isolates of Plasmodium falciparum and P. vivax. Antimicrobial Agents and Chemotherapy,55(3):961-966.

Document type: Journal Article
Attached Files (Some files may be inaccessible until you login with your CDU eSpace credentials)
Name Description MIMEType Size Downloads
Download this reading Marfurt_37591.pdf Published version application/pdf 337.20KB 119
Reading the attached file works best in Firefox, Chrome and IE 9 or later.

IRMA ID bsmithxPUB15
Title Ex vivo activity of histone deacetylase inhibitors against multidrug-resistant clinical isolates of Plasmodium falciparum and P. vivax
Author Marfurt, Jutta
Chalfein, Ferryanto
Prayoga, Pak
Wabiser, Frans
Kenangalem, Enny
Piera, Kim A.
Fairlie, David
Tjitra, Emiliana
Anstey, Nicholas M.
Andrews, Kathy
Price, Ric N.
Journal Name Antimicrobial Agents and Chemotherapy
Publication Date 2010
Volume Number 55
Issue Number 3
ISSN 0066-4804   (check CDU catalogue open catalogue search in new window)
Start Page 961
End Page 966
Total Pages 6
Place of Publication Washington , United States
Publisher American Society for Microbiology
HERDC Category C1 - Journal Article (DIISR)
Abstract Histone acetylation plays an important role in regulating gene transcription and silencing in Plasmodium falciparum. Histone deacetylase (HDAC) inhibitors, particularly those of the hydroxamate class, have been shown to have potent in vitro activity against drug-resistant and -sensitive laboratory strains of P. falciparum, raising their potential as a new class of antimalarial compounds. In the current study, stage-specific ex vivo susceptibility profiles of representative hydroxamate-based HDAC inhibitors suberoylanilide hydroxamic acid (SAHA), 2-ASA-9, and 2-ASA-14 (2-ASA-9 and 2-ASA-14 are 2-aminosuberic acid-based HDAC inhibitors) were assessed in multidrug-resistant clinical isolates of P. falciparum (n 24) and P. vivax (n 25) from Papua, Indonesia, using a modified schizont maturation assay. Submicromolar concentrations of SAHA, 2-ASA-9, and 2-ASA-14 inhibited the growth of both P. falciparum (median 50% inhibitory concentrations [IC50s] of 310, 533, and 266 nM) and P. vivax (median IC50s of 170, 503, and 278 nM). Inverse correlation patterns between HDAC inhibitors and chloroquine for P. falciparum and mefloquine for P. vivax indicate species-specific susceptibility profiles for HDAC inhibitors. These HDAC inhibitors were also found to be potent ex vivo against P. vivax schizont maturation, comparable to that in P. falciparum, suggesting that HDAC inhibitors may be promising candidates for antimalarial therapy in geographical locations where both species are endemic. Further studies optimizing the selectivity and in vivo efficacy of HDAC inhibitors in Plasmodium spp. and defining drug interaction with common antimalarial compounds are warranted to investigate the role of HDAC inhibitors in antimalarial therapy.
DOI http://dx.doi.org/10.1128/AAC.01220-10   (check subscription with CDU E-Gateway service for CDU Staff and Students  check subscription with CDU E-Gateway in new window)


© copyright

Every reasonable effort has been made to ensure that permission has been obtained for items included in CDU eSpace. If you believe that your rights have been infringed by this repository, please contact digitisation@cdu.edu.au.

 
Versions
Version Filter Type
Access Statistics: 96 Abstract Views, 119 File Downloads  -  Detailed Statistics
Created: Fri, 17 Jan 2014, 00:43:27 CST