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2,3-Diarylxanthones as potential inhibitors of Arachidonic acid metabolic pathways

dc.contributor.authorSantos, Clementina M.M.
dc.contributor.authorRibeiro, Daniela
dc.contributor.authorSilva, Artur
dc.contributor.authorFernandes, Eduarda
dc.date.accessioned2017-09-22T10:59:41Z
dc.date.available2017-09-22T10:59:41Z
dc.date.issued2017
dc.description.abstractIn response to an inflammatory stimulus, arachidonic acid (AA), the main polyunsaturated fatty acid present in the phospholipid layer of cell membranes, is released and metabolized to a series of eicosanoids. These bioactive lipid mediators of inflammation arise physiologically through the action of the enzymes 5-lipoxygenase (5-LOX) and cyclooxygenases (constitutive COX-1 and inducible COX-2). It is believed that dual inhibition of 5-LOX and COXs may have a higher beneficial impact in the treatment of inflammatory disorders rather than the inhibition of each enzyme. With this demand for new dual-acting anti-inflammatory agents, a range of 2,3-diarylxanthones were tested through their ability to interact in the AA metabolism. In vitro anti-inflammatory activity was evaluated through the inhibition of 5-LOX-catalyzed leukotriene B4 (LTB4) formation in human neutrophils and inhibition of COX-1- and COX-2-catalyzed prostaglandin E2 (PGE2) formation in human whole blood. The results showed that some of the studied arylxanthones were able to prevent LTB4 production in human neutrophils, in a concentration-dependent manner. The xanthone with a 2-catechol was the most active one (IC50 ∼ 9 μM). The more effective arylxanthones in preventing COX-1-catalyzed PGE2 production presented IC50 values from 1 to 7 μM, exhibiting a structural feature with at least one non-substituted aryl group. All the studied arylxanthones were ineffective to prevent the formation of PGE2 catalyzed by COX-2, up to the maximum concentration of 100 μM. The ability of the tested 2,3-diarylxanthones to interact with both 5-LOX and COX-1 pathways constitutes an important step in the research of novel dual-acting anti-inflammatory drugs.pt_PT
dc.description.sponsorshipSincere thanks are expressed to Faculdade de Farmácia da Universidade do Porto, Universidade de Aveiro, Instituto Politécnico de Bragança, Fundação para a Ciência e a Tecnologia (FCT, Portugal), Ministério da Educação e Ciência, European Union, FEDER, PT 2020, QREN, and COMPETE funding UCIBIO, REQUIMTE [(PT2020 UID/MULTI/04378/2013 - POCI/01/0145/FEDER/007728), (NORTE-01-0145-FEDER-000024), and (PTDC/QEQ-QAN/1742/2014 – POCI-01-0145- FEDER-016530)] and QOPNA (FCT UID/QUI/00062/2013) Research Units and also to the Portuguese National NMR Network (RNRMN). We gratefully acknowledge Graça Porto and the nursing staff of the Centro Hospitalar do Porto - Hospital de Santo António blood bank for the collaboration in the recruitment of blood donors involved in the present work.
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationSantos, Clementina M.M.; Ribeiro, Daniela; Silva, Artur; Fernandes, Eduarda (2017). 2,3-Diarylxanthones as potential inhibitors of Arachidonic acid metabolic pathways. Inflammation. ISSN 0360-3997. 40:3, p. 956-964
dc.identifier.doi10.1007/s10753-017-0540-6pt_PT
dc.identifier.urihttp://hdl.handle.net/10198/14519
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherSpringer Verlagpt_PT
dc.subjectXanthonespt_PT
dc.subject5-LOXpt_PT
dc.subjectCOX-1pt_PT
dc.subjectCOX-2pt_PT
dc.subjectHuman neutrophilspt_PT
dc.subjectHuman whole-blood assayspt_PT
dc.title2,3-Diarylxanthones as potential inhibitors of Arachidonic acid metabolic pathwayspt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/5876/UID%2FMulti%2F04378%2F2013/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/5876/UID%2FQUI%2F00062%2F2013/PT
oaire.citation.endPage964pt_PT
oaire.citation.issue3pt_PT
oaire.citation.startPage956pt_PT
oaire.citation.titleInflammationpt_PT
oaire.citation.volume40pt_PT
oaire.fundingStream5876
oaire.fundingStream5876
person.familyNameSantos
person.givenNameClementina M.M.
person.identifier.ciencia-id9018-DB9C-C590
person.identifier.orcid0000-0003-4380-7990
person.identifier.scopus-author-id7201458663
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublication64f662b6-775d-4ea0-bfd7-f527af0ac1a0
relation.isAuthorOfPublication.latestForDiscovery64f662b6-775d-4ea0-bfd7-f527af0ac1a0
relation.isProjectOfPublicationad309c78-04f5-4a7a-b692-8e54251249ee
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relation.isProjectOfPublication.latestForDiscoveryad309c78-04f5-4a7a-b692-8e54251249ee

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