Publicação
2,3-Diarylxanthones as potential inhibitors of Arachidonic acid metabolic pathways
| Resumo: | 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. |
|---|---|
| Autores principais: | Santos, Clementina M.M. |
| Outros Autores: | Ribeiro, Daniela; Silva, Artur; Fernandes, Eduarda |
| Assunto: | Xanthones 5-LOX COX-1 COX-2 Human neutrophils Human whole-blood assays |
| Ano: | 2017 |
| País: | Portugal |
| Tipo de documento: | artigo |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Instituto Politécnico de Bragança |
| Idioma: | inglês |
| Origem: | Biblioteca Digital do IPB |
| _version_ | 1867173122625503232 |
|---|---|
| author | Santos, Clementina M.M. |
| author2 | Ribeiro, Daniela Silva, Artur Fernandes, Eduarda |
| author2_role | author author author |
| author_facet | Santos, Clementina M.M. Ribeiro, Daniela Silva, Artur Fernandes, Eduarda |
| author_role | author |
| contributor_name_str_mv | Biblioteca Digital do IPB |
| country_str | PT |
| creators_json_txt | [{\"Person.name\":\"Santos, Clementina M.M.\",\"Person.identifier.orcid\":\"0000-0003-4380-7990\"},{\"Person.name\":\"Ribeiro, Daniela\"},{\"Person.name\":\"Silva, Artur\"},{\"Person.name\":\"Fernandes, Eduarda\"}] |
| datacite.contributors.contributor.contributorName.fl_str_mv | Biblioteca Digital do IPB |
| datacite.creators.creator.creatorName.fl_str_mv | Santos, Clementina M.M. Ribeiro, Daniela Silva, Artur Fernandes, Eduarda |
| datacite.date.Accepted.fl_str_mv | 2017-01-01T00:00:00Z |
| datacite.date.available.fl_str_mv | 2017-09-22T10:59:41Z |
| datacite.date.embargoed.fl_str_mv | 2017-09-22T10:59:41Z |
| datacite.rights.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| datacite.subjects.subject.fl_str_mv | Xanthones 5-LOX COX-1 COX-2 Human neutrophils Human whole-blood assays |
| datacite.titles.title.fl_str_mv | 2,3-Diarylxanthones as potential inhibitors of Arachidonic acid metabolic pathways |
| dc.contributor.none.fl_str_mv | Biblioteca Digital do IPB |
| dc.creator.none.fl_str_mv | Santos, Clementina M.M. Ribeiro, Daniela Silva, Artur Fernandes, Eduarda |
| dc.date.Accepted.fl_str_mv | 2017-01-01T00:00:00Z |
| dc.date.available.fl_str_mv | 2017-09-22T10:59:41Z |
| dc.date.embargoed.fl_str_mv | 2017-09-22T10:59:41Z |
| dc.format.none.fl_str_mv | application/pdf |
| dc.identifier.none.fl_str_mv | http://hdl.handle.net/10198/14519 |
| dc.language.none.fl_str_mv | eng |
| dc.publisher.none.fl_str_mv | Springer Verlag |
| dc.rights.none.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| dc.subject.none.fl_str_mv | Xanthones 5-LOX COX-1 COX-2 Human neutrophils Human whole-blood assays |
| dc.title.fl_str_mv | 2,3-Diarylxanthones as potential inhibitors of Arachidonic acid metabolic pathways |
| dc.type.none.fl_str_mv | http://purl.org/coar/resource_type/c_6501 |
| description | 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. |
| dirty | 0 |
| eu_rights_str_mv | openAccess |
| format | article |
| fulltext.url.fl_str_mv | https://bibliotecadigital.ipb.pt/bitstreams/292cb167-ce95-4d66-b8d0-6027e5a0b9d8/download |
| id | ipb_5945d2aaaab36292d8edfd9ccbf8df15 |
| identifier.url.fl_str_mv | http://hdl.handle.net/10198/14519 |
| instacron_str | ipb |
| institution | Instituto Politécnico de Bragança |
| instname_str | Instituto Politécnico de Bragança |
| language | eng |
| network_acronym_str | ipb |
| network_name_str | Biblioteca Digital do IPB |
| oai_identifier_str | oai:bibliotecadigital.ipb.pt:10198/14519 |
| organization_str_mv | urn:organizationAcronym:ipb |
| person_str_mv | Santos, Clementina M.M. Santos, Clementina M.M. https://www.ciencia-id.pt/9018-DB9C-C590 9018-DB9C-C590 http://orcid.org/0000-0003-4380-7990 0000-0003-4380-7990 Ribeiro, Daniela Silva, Artur Fernandes, Eduarda |
| publishDate | 2017 |
| publisher.none.fl_str_mv | Springer Verlag |
| reponame_str | Biblioteca Digital do IPB |
| repository_id_str | urn:repositoryAcronym:ipb |
| service_str_mv | urn:repositoryAcronym:ipb |
| spelling | engSpringer Verlagpt_PTIn 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.application/pdfpt_PT2,3-Diarylxanthones as potential inhibitors of Arachidonic acid metabolic pathwaysPersonalSantos, Clementina M.M.DSpacehttp://dspace.org/items/64f662b6-775d-4ea0-bfd7-f527af0ac1a0DSpacehttp://dspace.org/items/64f662b6-775d-4ea0-bfd7-f527af0ac1a0SantosClementina M.M.Ciência IDhttps://www.ciencia-id.pt9018-DB9C-C590ORCIDhttp://orcid.org0000-0003-4380-7990Scopus Author IDhttps://www.scopus.com7201458663Ribeiro, DanielaSilva, ArturFernandes, EduardaHostingInstitutionOrganizationalBiblioteca Digital do IPBe-mailmailto:dspace@ipb.ptdspace@ipb.ptDOIIsPartOf10.1007/s10753-017-0540-62017-09-22T10:59:41Z20172017-01-01T00:00:00ZHandlehttp://hdl.handle.net/10198/14519http://purl.org/coar/access_right/c_abf2open accessXanthones5-LOXCOX-1COX-2Human neutrophilsHuman whole-blood assays1259543 bytesliteraturehttp://purl.org/coar/resource_type/c_6501journal articlehttp://purl.org/coar/access_right/c_abf2application/pdffulltexthttps://bibliotecadigital.ipb.pt/bitstreams/292cb167-ce95-4d66-b8d0-6027e5a0b9d8/downloadInflammation403956964 |
| spellingShingle | 2,3-Diarylxanthones as potential inhibitors of Arachidonic acid metabolic pathways Santos, Clementina M.M. Xanthones 5-LOX COX-1 COX-2 Human neutrophils Human whole-blood assays |
| status | SINGLETON |
| subject.fl_str_mv | Xanthones 5-LOX COX-1 COX-2 Human neutrophils Human whole-blood assays |
| title | 2,3-Diarylxanthones as potential inhibitors of Arachidonic acid metabolic pathways |
| title_full | 2,3-Diarylxanthones as potential inhibitors of Arachidonic acid metabolic pathways |
| title_fullStr | 2,3-Diarylxanthones as potential inhibitors of Arachidonic acid metabolic pathways |
| title_full_unstemmed | 2,3-Diarylxanthones as potential inhibitors of Arachidonic acid metabolic pathways |
| title_short | 2,3-Diarylxanthones as potential inhibitors of Arachidonic acid metabolic pathways |
| title_sort | 2,3-Diarylxanthones as potential inhibitors of Arachidonic acid metabolic pathways |
| topic | Xanthones 5-LOX COX-1 COX-2 Human neutrophils Human whole-blood assays |
| topic_facet | Xanthones 5-LOX COX-1 COX-2 Human neutrophils Human whole-blood assays |
| url | http://hdl.handle.net/10198/14519 |
| visible | 1 |