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Rosette-Disrupting Effect of an Anti-Plasmodial Compound for the Potential Treatment of Plasmodium falciparum Malaria Complications

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dc.creatorCh’ng, Jun-Hong
dc.creatorMoll, Kirsten
dc.creatorQuintana, Maria del Pilar
dc.creatorLeung Chan, Sherwin Chun
dc.creatorMasters, Ellen
dc.creatorMoles, Ernest
dc.creatorLiu, Jianping
dc.creatorEriksson, Anders
dc.creatorWahlgren, Mats
dc.creator.googleCh'ng, J.-H.spa
dc.creator.googleMoll, K.spa
dc.creator.googleQuintana, M.D.P.spa
dc.creator.googleChan, S.C.L.spa
dc.creator.googleMasters, E.spa
dc.creator.googleMoles, E.spa
dc.creator.googleLiu, J.spa
dc.creator.googleEriksson, Anders B.spa
dc.creator.googleWahlgren, M.spa
dc.date.accessioned2020-05-08T00:49:30Z
dc.date.available2020-05-08T00:49:30Z
dc.date.created2016-07-11
dc.date.issued2016
dc.description.abstractThe spread of artemisinin-resistant parasites could lead to higher incidence of patients with malaria complications. However, there are no current treatments that directly dislodge sequestered parasites from the microvasculature. We show that four common antiplasmodial drugs do not disperse rosettes (erythrocyte clusters formed by malaria parasites) and therefore develop a cell-based high-throughput assay to identify potential rosette-disrupting compounds. A pilot screen of 2693 compounds identified Malaria Box compound MMV006764 as a potential candidate. Although it reduced rosetting by a modest 20%, MMV006764 was validated to be similarly effective against both blood group O and A rosettes of three laboratory parasite lines. Coupled with its antiplasmodial activity and drug-likeness, MMV006764 represents the first small-molecule compound that disrupts rosetting and could potentially be used in a resource-limited setting to treat patients deteriorating rapidly from malaria complications. Such dual-action drugs that simultaneously restore microcirculation and reduce parasite load could significantly reduce malaria morbidity and mortality.eng
dc.format.mimetypeapplication/pdf
dc.identifier.doihttps://doi.org/10.1038/srep29317
dc.identifier.issn2045-2322
dc.identifier.urihttps://repository.urosario.edu.co/handle/10336/21912
dc.language.isoeng
dc.relation.citationTitleScientific Reports
dc.relation.citationVolumeVol. 6
dc.relation.ispartofScientific Reports, ISSN: 2045-2322 Vol. 6, (Julio 2016); 13 pp.spa
dc.relation.urihttps://www.nature.com/articles/srep29317
dc.rights.accesRightsinfo:eu-repo/semantics/openAccess
dc.rights.accesoAbierto (Texto Completo)spa
dc.source.instnameinstname:Universidad del Rosario
dc.source.reponamereponame:Repositorio Institucional EdocUR
dc.subjectPlasmodium falciparumeng
dc.subjectAnimalseng
dc.subjectAntimalarialseng
dc.subjectArtemisininseng
dc.subjectDrug Discoveryeng
dc.subjectDrug Resistanceeng
dc.subjectErythrocyteseng
dc.subjectHigh-Throughput Screening Assayseng
dc.subjectMicrocirculationeng
dc.subjectMicrovesselseng
dc.subjectParasite Loadeng
dc.subjectPlasmodium falciparumeng
dc.subjectPyridineseng
dc.subject.ddcIncidencia & prevención de la enfermedadspa
dc.titleRosette-Disrupting Effect of an Anti-Plasmodial Compound for the Potential Treatment of Plasmodium falciparum Malaria Complicationsspa
dc.typearticleeng
dc.type.hasVersioninfo:eu-repo/semantics/publishedVersion
dc.type.spaArtículospa
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