dc.creator | Schaeffer, Evelyne | es |
dc.creator | Sánchez Fernández, Elena Matilde | es |
dc.creator | Gonçalves-Pereira, Rita | es |
dc.creator | Flacher, Vincent | es |
dc.creator | Lamon, Delphine | es |
dc.creator | Duval, Monique | es |
dc.creator | Fauny, Jean Daniel | es |
dc.creator | García Fernández, José Manuel | es |
dc.creator | Mueller, Christopher G. | es |
dc.creator | Ortiz Mellet, Carmen | es |
dc.date.accessioned | 2022-12-15T16:17:30Z | |
dc.date.available | 2022-12-15T16:17:30Z | |
dc.date.issued | 2019 | |
dc.identifier.citation | Schaeffer, E., Sánchez Fernández, E.M., Gonçalves-Pereira, R., Flacher, V., Lamon, D., Duval, M.,...,Ortiz Mellet, C. (2019). sp2-Iminosugar Glycolipids as Inhibitors of Lipopolysaccharide-mediated Human Dendritic Cell Activation in Vitro and of Acute Inflammation in Mice in Vivo. European Journal of Medicinal Chemistry, 169, 111-120. https://doi.org/10.1016/j.ejmech.2019.02.078. | |
dc.identifier.issn | 0223-5234 | es |
dc.identifier.issn | 1768-3254 | es |
dc.identifier.uri | https://hdl.handle.net/11441/140526 | |
dc.description.abstract | Glycolipid mimetics consisting of a bicyclic polyhydroxypiperidine-cyclic carbamate core and a pseudoanomeric hydrophobic tail, termed sp2-iminosugar glycolipids (sp2-IGLs), target microglia during neuroinflammatory processes. Here we have synthesized and investigated new variants of sp2-IGLs for their ability to suppress the activation of human monocyte-derived dendritic cells (DCs) by lipopolysaccharide (LPS) signaling through Toll-like receptor 4. We report that the best lead was (1R)-1-dodecylsulfonyl-5N,6O-oxomethylidenenojirimycin (DSO2-ONJ), able to inhibit LPS-induced TNFα production and maturation of DCs. Immunovisualization experiments, using a mannoside glycolipid conjugate (MGC) that also suppress LPS-mediated DC activation as control, evidenced a distinct mode of action for the sp2-IGLs: unlike MGCs, DSO2-ONJ did not elicit internalization of the LPS co-receptor CD14 or induce its co-localization with the Toll-like receptor 4. In a mouse model of LPS-induced acute inflammation, DSO2-ONJ demonstrated anti-inflammatory activity by inhibiting the production of the pro-inflammatory interleukin-6. The ensemble of the data highlights sp2-IGLs as a promising new class of molecules against inflammation by interfering in Toll-like receptor intracellular signaling. | es |
dc.description.sponsorship | Centre national de la recherche scientifique ANR-10-LABX-0034 MEDALIS, ANR-11-EQPX-022 | es |
dc.description.sponsorship | Ministerio de Economía y Competitividad SAF2016-76083-R, CTQ2015-64425-C2-1-R | es |
dc.format | application/pdf | es |
dc.format.extent | 26 p. | es |
dc.language.iso | eng | es |
dc.publisher | Elsevier | es |
dc.relation.ispartof | European Journal of Medicinal Chemistry, 169, 111-120. | |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.subject | Dendritic cell | es |
dc.subject | Glycolipid | es |
dc.subject | Iminosugar | es |
dc.subject | Inflammation | es |
dc.subject | Sulfone | es |
dc.subject | Sulfoxide | es |
dc.title | sp2-Iminosugar Glycolipids as Inhibitors of Lipopolysaccharide-mediated Human Dendritic Cell Activation in Vitro and of Acute Inflammation in Mice in Vivo | es |
dc.type | info:eu-repo/semantics/article | es |
dcterms.identifier | https://ror.org/03yxnpp24 | |
dc.type.version | info:eu-repo/semantics/acceptedVersion | es |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es |
dc.contributor.affiliation | Universidad de Sevilla. Departamento de Química orgánica | es |
dc.relation.projectID | ANR-10-LABX-0034 MEDALIS | es |
dc.relation.projectID | ANR-11-EQPX-022 | es |
dc.relation.projectID | SAF2016-76083-R | es |
dc.relation.projectID | CTQ2015-64425-C2-1-R | es |
dc.relation.publisherversion | https://doi.org/10.1016/j.ejmech.2019.02.078 | es |
dc.identifier.doi | 10.1016/j.ejmech.2019.02.078 | es |
dc.journaltitle | European Journal of Medicinal Chemistry | es |
dc.publication.volumen | 169 | es |
dc.publication.initialPage | 111 | es |
dc.publication.endPage | 120 | es |
dc.contributor.funder | Centre national de la recherche scientifique (CNRS). France | es |
dc.contributor.funder | Ministerio de Economía y Competitividad (MINECO). España | es |