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dc.contributor.authorAndrews, KT
dc.contributor.authorTran, TN
dc.contributor.authorLucke, AJ
dc.contributor.authorKahnberg, P
dc.contributor.authorLe, GT
dc.contributor.authorBoyle, GM
dc.contributor.authorGardiner, DL
dc.contributor.authorSkinner-Adams, TS
dc.contributor.authorFairlie, DP
dc.date.accessioned2017-09-05T05:51:43Z
dc.date.available2017-09-05T05:51:43Z
dc.date.issued2008
dc.date.modified2009-10-21T05:33:58Z
dc.identifier.issn0066-4804
dc.identifier.doi10.1128/AAC.00757-07
dc.identifier.urihttp://hdl.handle.net/10072/26152
dc.description.abstractThe 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.
dc.description.peerreviewedYes
dc.description.publicationstatusYes
dc.languageEnglish
dc.language.isoen_AU
dc.publisherAmerican Society for Microbiology
dc.publisher.placeUSA
dc.relation.ispartofstudentpublicationY
dc.relation.ispartofpagefrom1454
dc.relation.ispartofpageto1461
dc.relation.ispartofissue4
dc.relation.ispartofjournalAntimicrobial Agents and Chemotherapy
dc.relation.ispartofvolume52
dc.rights.retentionY
dc.subject.fieldofresearchMicrobiology
dc.subject.fieldofresearchMedical Microbiology
dc.subject.fieldofresearchPharmacology and Pharmaceutical Sciences
dc.subject.fieldofresearchcode0605
dc.subject.fieldofresearchcode1108
dc.subject.fieldofresearchcode1115
dc.titlePotent antimalarial activity of histone deacetylase inhibitor analogues
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.facultyGriffith Sciences, School of Natural Sciences
gro.rights.copyright© 2008 American Society for Microbiology. The attached file is reproduced here in accordance with the copyright policy of the publisher. Please refer to the journal's website for access to the definitive, published version.
gro.date.issued2008
gro.hasfulltextFull Text
gro.griffith.authorAndrews, Katherine T.
gro.griffith.authorGardiner, Donald
gro.griffith.authorTran, Thanh
gro.griffith.authorSkinner-Adams, Tina


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