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dc.creatorCvijetić, Ilija
dc.creatorTanc, Muhammet
dc.creatorJuranić, Ivan
dc.creatorVerbić, Tatjana
dc.creatorSupuran, Claudiu T.
dc.creatorDrakulić, Branko
dc.date.accessioned2019-04-20T12:46:31Z
dc.date.available2017-06-05
dc.date.issued2015
dc.identifier.issn0968-0896
dc.identifier.urihttps://cer.ihtm.bg.ac.rs/handle/123456789/2668
dc.description.abstractInhibitory activity of a congeneric set of 23 phenyl-substituted 5-phenyl-pyrazole-3-carboxylic acids toward human carbonic anhydrase (hCA, EC 4.2.1.1) isoforms I, II, IX and XII was evaluated by a stopped-flow CO2 hydrase assay. These compounds exerted a clear, selective inhibition of hCA IX and XII over hCAI and II, with Ki in two to one digit micromolar concentrations (4-50 mu M). Derivatives bearing bulkier substituents in para-position of the phenyl ring inhibited hCA XII at one-digit micromolar concentrations, while derivatives having alkyl substituents in both ortho-and meta-positions inhibited hCA IX with Kis ranging between 5 and 25 mu M. Results of docking experiments offered a rational explanation on the selectivity of these compounds toward CA IX and XII, as well as on the substitution patterns leading to best CA IX or CA XII inhibitors. By examining the active sites of these four isoforms with GRID generated molecular-interaction fields, striking differences between hCA XII and the other three isoforms were observed. The field of hydrophobic probe (DRY) appeared significantly different in CA XII active site, comparing to other three isoforms studied. To the best of our knowledge such an observation was not reported in literature so far. Considering the selectivity of these carboxylates towards membrane-associated over cytosolic CA isoforms, the title compounds could be useful for the development of isoform-specific non-sulfonamide CA inhibitors. (C) 2015 Elsevier Ltd. All rights reserved.en
dc.publisherOxford : Pergamon-Elsevier Science Ltd
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/172035/RS//
dc.rightsembargoedAccess
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.sourceBioorganic and Medicinal Chemistry
dc.subjectCarbonic anhydraseen
dc.subjectPhenyl-pyrazole-carboxylic acidsen
dc.subjectDockingen
dc.subjectMolecular interaction fieldsen
dc.subjectActive sites comparisonen
dc.title5-Aryl-1H-pyrazole-3-carboxylic acids as selective inhibitors of human carbonic anhydrases IX and XIIen
dc.typearticle
dc.rights.licenseBY-NC-ND
dcterms.abstractЦвијетић, Илија; Танц, Мухаммет; Вербић, Татјана; Супуран, Цлаудиу Т.; Дракулиц, Бранко; Јуранић, Иван;
dc.citation.volume23
dc.citation.issue15
dc.citation.spage4649
dc.citation.epage4659
dc.citation.other23(15): 4649-4659
dc.citation.rankM21
dc.description.otherThis is the peer-reviewed version of the article: [https://doi.org/10.1016/j.bmc.2015.05.052]
dc.description.otherThe published version of the article: [http://cer.ihtm.bg.ac.rs/handle/123456789/2872]
dc.identifier.pmid26088336
dc.identifier.doi10.1016/j.bmc.2015.05.052
dc.identifier.fulltexthttps://cer.ihtm.bg.ac.rs/bitstream/id/6328/10.1016@j.bmc.2015.05.052_accepted.pdf
dc.identifier.scopus2-s2.0-84937818628
dc.identifier.wos000358440000055
dc.type.versionacceptedVersionen


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