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dc.contributor.authorMujumdar, P
dc.contributor.authorBua, S
dc.contributor.authorSupuran, CT
dc.contributor.authorPeat, TS
dc.contributor.authorPoulsen, SA
dc.date.accessioned2019-07-04T12:41:19Z
dc.date.available2019-07-04T12:41:19Z
dc.date.issued2018
dc.identifier.issn0960-894X
dc.identifier.doi10.1016/j.bmcl.2018.04.038
dc.identifier.urihttp://hdl.handle.net/10072/381695
dc.description.abstractHere we report the synthesis of natural products (NPs) 5′-O-sulfamoyl adenosine 1 and 5′-O-sulfamoyl-2-chloroadenosine 2. As primary sulfamates these compounds represent an uncommon class of NPs, furthermore there are few NPs known that contain a NS bond. Compounds 1 and 2 were evaluated for inhibition of carbonic anhydrases (CA), a metalloenzyme family where the primary sulfamate is known to coordinate to the active site zinc and form key hydrogen bonds with adjacent CA active site residues. Both NPs were good to moderate CA inhibitors, with compound 2 a 20–50-fold stronger CA inhibitor (Ki values 65–234 nM) than compound 1. The protein X-ray crystal structures of 1 and 2 in complex with CA II show that it is not the halogen-hydrophobic interactions that give compound 2 a greater binding energy but a slight movement in orientation of the ribose ring that allows better hydrogen bonds to CA residues. Compounds 1 and 2 were further investigated for antimicrobial activity against a panel of microbes relevant to human health, including Gram-negative bacteria (4 strains), Gram-positive bacteria (1 strain) and yeast (2 strains). Antimicrobial activity and selectivity was observed. The minimum inhibitory concentration (MIC) of NP 1 was 10 µM against Gram-positive Staphylococcus aureus and NP 2 was 5 µM against Gram-negative Escherichia coli. This is the first time that NP primary sulfamates have been assessed for inhibition and binding to CAs, with systematic antimicrobial activity studies also reported.
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publisherElsevier
dc.publisher.placeUnited Kingdom
dc.relation.ispartofpagefrom3009
dc.relation.ispartofpageto3013
dc.relation.ispartofissue17
dc.relation.ispartofjournalBioorganic & Medicinal Chemistry Letters
dc.relation.ispartofvolume28
dc.subject.fieldofresearchMedicinal and biomolecular chemistry
dc.subject.fieldofresearchOrganic chemistry
dc.subject.fieldofresearchOrganic chemistry not elsewhere classified
dc.subject.fieldofresearchPharmacology and pharmaceutical sciences
dc.subject.fieldofresearchcode3404
dc.subject.fieldofresearchcode3405
dc.subject.fieldofresearchcode340599
dc.subject.fieldofresearchcode3214
dc.subject.keywordsCarbonic anhydrase
dc.subject.keywordsInhibitor
dc.subject.keywordsNatural product
dc.subject.keywordsSulfamate
dc.subject.keywordsNucleoside
dc.subject.keywordsAntimicrobial
dc.titleSynthesis, structure and bioactivity of primary sulfamate-containing natural products
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
dcterms.licensehttp://creativecommons.org/licenses/by-nc-nd/4.0/
gro.facultyGriffith Sciences, School of Environment and Science
gro.rights.copyright© 2018 Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International Licence (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.authorPoulsen, Sally-Ann


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