Publication
2,3-Diarylxanthones as potential inhibitors of Arachidonic acid metabolic pathways
dc.contributor.author | Santos, Clementina M.M. | |
dc.contributor.author | Ribeiro, Daniela | |
dc.contributor.author | Silva, Artur | |
dc.contributor.author | Fernandes, Eduarda | |
dc.date.accessioned | 2017-09-22T10:59:41Z | |
dc.date.available | 2017-09-22T10:59:41Z | |
dc.date.issued | 2017 | |
dc.description.abstract | In 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.sponsorship | Sincere 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.version | info:eu-repo/semantics/publishedVersion | pt_PT |
dc.identifier.citation | Santos, 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.doi | 10.1007/s10753-017-0540-6 | pt_PT |
dc.identifier.uri | http://hdl.handle.net/10198/14519 | |
dc.language.iso | eng | pt_PT |
dc.peerreviewed | yes | pt_PT |
dc.publisher | Springer Verlag | pt_PT |
dc.subject | Xanthones | pt_PT |
dc.subject | 5-LOX | pt_PT |
dc.subject | COX-1 | pt_PT |
dc.subject | COX-2 | pt_PT |
dc.subject | Human neutrophils | pt_PT |
dc.subject | Human whole-blood assays | pt_PT |
dc.title | 2,3-Diarylxanthones as potential inhibitors of Arachidonic acid metabolic pathways | pt_PT |
dc.type | journal article | |
dspace.entity.type | Publication | |
oaire.awardURI | info:eu-repo/grantAgreement/FCT/5876/UID%2FMulti%2F04378%2F2013/PT | |
oaire.awardURI | info:eu-repo/grantAgreement/FCT/5876/UID%2FQUI%2F00062%2F2013/PT | |
oaire.citation.endPage | 964 | pt_PT |
oaire.citation.issue | 3 | pt_PT |
oaire.citation.startPage | 956 | pt_PT |
oaire.citation.title | Inflammation | pt_PT |
oaire.citation.volume | 40 | pt_PT |
oaire.fundingStream | 5876 | |
oaire.fundingStream | 5876 | |
person.familyName | Santos | |
person.givenName | Clementina M.M. | |
person.identifier.ciencia-id | 9018-DB9C-C590 | |
person.identifier.orcid | 0000-0003-4380-7990 | |
person.identifier.scopus-author-id | 7201458663 | |
project.funder.identifier | http://doi.org/10.13039/501100001871 | |
project.funder.identifier | http://doi.org/10.13039/501100001871 | |
project.funder.name | Fundação para a Ciência e a Tecnologia | |
project.funder.name | Fundação para a Ciência e a Tecnologia | |
rcaap.rights | openAccess | pt_PT |
rcaap.type | article | pt_PT |
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