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dc.contributor.authorVullo, Daniela
dc.contributor.authorDel Prete, Sonia
dc.contributor.authorFisher, Gillian M
dc.contributor.authorAndrews, Katherine T
dc.contributor.authorPoulsen, Sally-Ann
dc.contributor.authorCapasso, Clemente
dc.contributor.authorSupuran, Claudiu T
dc.date.accessioned2018-05-03T01:00:31Z
dc.date.available2018-05-03T01:00:31Z
dc.date.issued2015
dc.identifier.issn0968-0896
dc.identifier.doi10.1016/j.bmc.2014.12.009
dc.identifier.urihttp://hdl.handle.net/10072/142232
dc.description.abstractThe η-carbonic anhydrases (CAs, EC 4.2.1.1) were recently discovered as the sixth genetic class of this metalloenzyme superfamily, and are so far known only in protozoa, including various Plasmodium species, the causative agents of malaria. We report here an inhibition study of the η-CA from Plasmodium falciparum (PfCA) against a panel of sulfonamides and one sulfamate compound, some of which are clinically used. The strongest inhibitors identified were ethoxzolamide and sulthiame, with KIs of 131–132 nM, followed by acetazolamide, methazolamide and hydrochlorothiazide (KIs of 153–198 nM). Brinzolamide, topiramate, zonisamide, indisulam, valdecoxib and celecoxib also showed significant inhibitory action against PfCA, with KIs ranging from 217 to 308 nM. An interesting observation was that the more efficient PfCA inhibitors are representative of several scaffolds and chemical classes, including benzene sulfonamides, monocyclic/bicyclic heterocyclic sulfonamides and compounds with a more complex scaffold (i.e., the sugar sulfamate derivative, topiramate, and the coxibs, celecoxib and valdecoxib). A comprehensive inhibition study of small molecules for η-CAs is needed as a first step towards assessing PfCA as a druggable target. The present work identifies the first known η-CA inhibitors and provides a platform for the development of next generation novel PfCA inhibitors.
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publisherPergamon
dc.relation.ispartofpagefrom526
dc.relation.ispartofpageto531
dc.relation.ispartofjournalBioorganic & Medicinal Chemistry
dc.relation.ispartofvolume23
dc.subject.fieldofresearchOrganic Chemistry not elsewhere classified
dc.subject.fieldofresearchMedicinal and Biomolecular Chemistry
dc.subject.fieldofresearchOrganic Chemistry
dc.subject.fieldofresearchPharmacology and Pharmaceutical Sciences
dc.subject.fieldofresearchcode030599
dc.subject.fieldofresearchcode0304
dc.subject.fieldofresearchcode0305
dc.subject.fieldofresearchcode1115
dc.titleSulfonamide inhibition studies of the n-class carbonic anhydrase from the malaria pathogen Plasmodium falciparum
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.hasfulltextNo Full Text
gro.griffith.authorAndrews, Katherine T.
gro.griffith.authorPoulsen, Sally-Ann
gro.griffith.authorFisher, Gill M.


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