Potent antimalarial activity of histone deacetylase inhibitor analogues.

Potent antimalarial activity of histone deacetylase inhibitor analogues. Research Abstract Details 

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Potent antimalarial activity of histone deacetylase inhibitor analogues. Abstract Text:

K T Andrews,T N Tran,A J Lucke,P Kahnberg,G T Le,G M Boyle,D L Gardiner,T S Skinner-Adams,D P Fairlie,

The malaria parasite Plasmodium falciparum has at least five putative histone deacetylase (HDAC) enzymes, which have been proposed as new antimalarial drug targets and may play roles in regulating gene transcription, like the better-known and more intensively studied human HDACs (hHDACs). Fourteen new compounds derived from l-cysteine or 2-aminosuberic acid were designed to inhibit P. falciparum HDAC-1 (PfHDAC-1) based on homology modeling with human class I and class II HDAC enzymes. The compounds displayed highly potent antiproliferative activity against drug-resistant (Dd2) or drug sensitive (3D7) strains of P. falciparum in vitro (50% inhibitory concentration of 13 to 334 nM). Unlike known hHDAC inhibitors, some of these new compounds were significantly more toxic to P. falciparum parasites than to mammalian cells. The compounds inhibited P. falciparum growth in erythrocytes at both the early and late stages of the parasite's life cycle and caused altered histone acetylation patterns (hyperacetylation), which is a marker of HDAC inhibition in mammalian cells. These results support PfHDAC enzymes as being promising targets for new antimalarial drugs.

Potent antimalarial activity of histone deacetylase inhibitor analogues. Publishing Authors By Initials

KT Andrews,TN Tran,AJ Lucke,P Kahnberg,GT Le,GM Boyle,DL Gardiner,TS Skinner-Adams,DP Fairlie,

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Potent antimalarial activity of histone deacetylase inhibitor analogues. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Antimicrobial agents and chemotherapy

VOLUME: 52

Page Numbers: 1454-61

Journal Abbreviation: Antimicrob. Agents Chemother.

ISSN: 0066-4804

DAY: 22

MONTH: 01

YEAR: 2008

Potent antimalarial activity of histone deacetylase inhibitor analogues. Information

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LANGUAGE: eng

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AFFILIATION: Clinical Tropical Medicine Laboratory, Queensland Institute of Medical Research, P.O. Box Royal Brisbane Hospital, Herston, Queensland 4029, Australia. kathy.andrews@qimr.edu.au.

Country: United States

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MEDLINETA: Antimicrob Agents Chemother

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