Show simple item record

dc.contributor.authorVaidya, Akhil B.
dc.contributor.authorMorrisey, Joanne M.
dc.contributor.authorZhang, Zhongsheng
dc.contributor.authorDas, Sudipta
dc.contributor.authorDaly, Thomas M.
dc.contributor.authorOtto, Thomas D.
dc.contributor.authorSpillman, Natalie J.
dc.contributor.authorWyvratt, Matthew
dc.contributor.authorSiegl, Peter
dc.contributor.authorMarfurt, Jutta
dc.contributor.authorWirjanata, Grennady
dc.contributor.authorSebayang, Boni F.
dc.contributor.authorPrice, Ric N.
dc.contributor.authorChatterjee, Arnab
dc.contributor.authorNagle, Advait
dc.contributor.authorStasiak, Marcin
dc.contributor.authorCharman, Susan A.
dc.contributor.authorAngulo-Barturen, Inigo
dc.contributor.authorFerrer, Santiago
dc.contributor.authorJimenez-Diaz, Maria Belen
dc.contributor.authorMartinez, Maria Santos
dc.contributor.authorGamo, Francisco Javier
dc.contributor.authorAvery, Vicky
dc.contributor.authorRuecker, Andrea
dc.contributor.authorDelves, Michael
dc.contributor.authorKirk, Kiaran
dc.contributor.authorBerriman, Matthew
dc.contributor.authorKortagere, Sandhya
dc.contributor.authorBurrows, Jeremy
dc.contributor.authoret al.
dc.date.accessioned2017-09-15T04:36:07Z
dc.date.available2017-09-15T04:36:07Z
dc.date.issued2014
dc.identifier.issn2041-1723en_US
dc.identifier.doi10.1038/ncomms6521en_US
dc.identifier.urihttp://hdl.handle.net/10072/124827
dc.description.abstractThe quest for new antimalarial drugs, especially those with novel modes of action, is essential in the face of emerging drug-resistant parasites. Here we describe a new chemical class of molecules, pyrazoleamides, with potent activity against human malaria parasites and showing remarkably rapid parasite clearance in an in vivo model. Investigations involving pyrazoleamide-resistant parasites, whole-genome sequencing and gene transfers reveal that mutations in two proteins, a calcium-dependent protein kinase (PfCDPK5) and a P-type cation-ATPase (PfATP4), are necessary to impart full resistance to these compounds. A pyrazoleamide compound causes a rapid disruption of Na+ regulation in blood-stage Plasmodium falciparum parasites. Similar effect on Na+ homeostasis was recently reported for spiroindolones, which are antimalarials of a chemical class quite distinct from pyrazoleamides. Our results reveal that disruption of Na+ homeostasis in malaria parasites is a promising mode of antimalarial action mediated by at least two distinct chemical classes.en_US
dc.description.peerreviewedYesen_US
dc.languageEnglishen_US
dc.publisherNature Publishing Groupen_US
dc.publisher.placeUnited Kingdomen_US
dc.relation.ispartofpagefrom5521-1en_US
dc.relation.ispartofpageto5521-10en_US
dc.relation.ispartofjournalNature Communicationsen_US
dc.relation.ispartofvolume5en_US
dc.subject.fieldofresearchMedicinal and Biomolecular Chemistry not elsewhere classifieden_US
dc.subject.fieldofresearchcode030499en_US
dc.titlePyrazoleamide compounds are potent antimalarials that target Na+ homeostasis in intraerythrocytic Plasmodium falciparumen_US
dc.typeJournal articleen_US
dc.type.descriptionC1 - Peer Reviewed (HERDC)en_US
dc.type.codeC - Journal Articlesen_US
dcterms.licensehttp://creativecommons.org/licenses/by/4.0/en_US
dc.description.versionPublisheden_US
gro.rights.copyright© The Author(s) 2014. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/en_US
gro.hasfulltextFull Text


Files in this item

This item appears in the following Collection(s)

  • Journal articles
    Contains articles published by Griffith authors in scholarly journals.

Show simple item record