Show simple item record

dc.contributor.authorFisher, Gillian M
dc.contributor.authorBua, Silvia
dc.contributor.authorDel Prete, Sonia
dc.contributor.authorArnold, Megan SJ
dc.contributor.authorCapasso, Clemente
dc.contributor.authorSupuran, Claudiu T
dc.contributor.authorAndrews, Katherine T
dc.contributor.authorPoulsen, Sally-Ann
dc.date.accessioned2017-08-17T06:01:57Z
dc.date.available2017-08-17T06:01:57Z
dc.date.issued2017
dc.identifier.issn2211-3207
dc.identifier.doi10.1016/j.ijpddr.2017.01.003
dc.identifier.urihttp://hdl.handle.net/10072/344425
dc.description.abstractIn the past decade there has been a significant reduction in deaths due to malaria, in part due to the success of the gold standard antimalarial treatment - artemisinin combination therapies (ACTs). However the potential threat of ACT failure and the lack of a broadly effective malaria vaccine are driving efforts to discover new chemical entities (NCEs) to target this disease. The primary sulfonamide (PS) moiety is a component of several clinical drugs, including those for treatment of kidney disease, glaucoma and epilepsy, however this chemotype has not yet been exploited for malaria. In this study 31 PS compounds sourced from the GlaxoSmithKline (GSK) Tres Cantos antimalarial set (TCAMS) were investigated for their ability to selectively inhibit the in vitro growth of Plasmodium falciparum asexual stage malaria parasites. Of these, 14 compounds were found to have submicromolar activity (IC50 0.16–0.89 μM) and a modest selectivity index (SI) for the parasite versus human cells (SI > 12 to >43). As the PS moiety is known to inhibit carbonic anhydrase (CA) enzymes from many organisms, the PS compounds were assessed for recombinant P. falciparum CA (PfCA) mediated inhibition of CO2 hydration. The PfCA inhibition activity did not correlate with antiplasmodial potency. Furthermore, no significant difference in IC50 was observed for P. falciparum versus P. knowlesi (P > 0.05), a Plasmodium species that is not known to contain an annotated PfCA gene. Together these data suggest that the asexual intraerythrocytic stage antiplasmodial activity of the PS compounds examined in this study is likely unrelated to PfCA inhibition.
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publisherElsevier
dc.relation.ispartofpagefrom61
dc.relation.ispartofpageto70
dc.relation.ispartofjournalInternational Journal for Parasitology: Drugs and Drug Resistance
dc.relation.ispartofvolume7
dc.subject.fieldofresearchMedical microbiology
dc.subject.fieldofresearchMedical microbiology not elsewhere classified
dc.subject.fieldofresearchMicrobiology
dc.subject.fieldofresearchcode3207
dc.subject.fieldofresearchcode320799
dc.subject.fieldofresearchcode3107
dc.titleInvestigating the antiplasmodial activity of primary sulfonamide compounds identified in open source malaria data
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
dcterms.licensehttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.description.versionVersion of Record (VoR)
gro.facultyGriffith Sciences, School of Natural Sciences
gro.rights.copyright© 2017 The Authors. Published by Elsevier Ltd on behalf of Australian Society for Parasitology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, providing that the work is properly cited.
gro.hasfulltextFull Text
gro.griffith.authorAndrews, Katherine T.
gro.griffith.authorPoulsen, Sally-Ann
gro.griffith.authorFisher, Gill M.


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