dc.creator | Rodríguez Lavado, Julio | es |
dc.creator | Sestito, Stefania E. | es |
dc.creator | Cighetti, Roberto | es |
dc.creator | Aguilar Moncayo, Eva M. | es |
dc.creator | Oblak, Alja | es |
dc.creator | Lainšček, Duško | es |
dc.creator | Jiménez Blanco, José Luis | es |
dc.creator | García Fernández, José Manuel | es |
dc.creator | Ortiz Mellet, Carmen | es |
dc.creator | Jerala, Roman | es |
dc.creator | Calabrese, Valentina | es |
dc.creator | Peri, Francesco | es |
dc.date.accessioned | 2018-09-18T10:35:23Z | |
dc.date.available | 2018-09-18T10:35:23Z | |
dc.date.issued | 2014 | |
dc.identifier.citation | Rodríguez Lavado, J., Sestito, S.E., Cighetti, R., Aguilar Moncayo, E.M., Oblak, A., Lainšček, D.,...,Peri, F. (2014). Trehalose- and Glucose-Derived Glycoamphiphiles: Small-Molecule and Nanoparticle Toll-Like Receptor 4 (TLR4) Modulators. Journal of Medicinal Chemistry, 57 (21), 9105-9123. | |
dc.identifier.issn | 0022-2623 (impreso) | es |
dc.identifier.issn | 1520-4804 (electrónico) | es |
dc.identifier.uri | https://hdl.handle.net/11441/78585 | |
dc.description.abstract | An increasing number of pathologies have been linked to Toll-like receptor 4 (TLR4) activation and signaling, therefore new hit and lead compounds targeting this receptor activation process are urgently needed. We report on the synthesis and biological properties of glycolipids based on glucose and trehalose scaffolds which potently inhibit TLR4 activation and signaling in vitro and in vivo. Structure–activity relationship studies on these compounds indicate that the presence of fatty ester chains in the molecule is a primary prerequisite for biological activity and point to facial amphiphilicity as a preferred architecture for TLR4 antagonism. The cationic glycolipids here presented can be considered as new lead compounds for the development of drugs targeting TLR4 activation and signaling in infectious, inflammatory, and autoimmune diseases. Interestingly, the biological activity of the best drug candidate was retained after adsorption at the surface of colloidal gold nanoparticles, broadening the options for clinical development. | es |
dc.description.sponsorship | Italian, Ministry of University and Research (MIUR), PRIN 2010 - 11 | es |
dc.description.sponsorship | Ministerio de Economía y Competitividad AF2013-44021- R, CTQ2010 - 15848 | es |
dc.description.sponsorship | Junta de Andalucía FQM 1467 | es |
dc.description.sponsorship | Slovenian Research Agency P4-176, J1 - 4170 | es |
dc.format | application/pdf | es |
dc.language.iso | eng | es |
dc.publisher | American Chemical Society | es |
dc.relation.ispartof | Journal of Medicinal Chemistry, 57 (21), 9105-9123. | |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.subject | TLR4 | es |
dc.subject | MD-2 | es |
dc.subject | CD14 | es |
dc.subject | Lipid A | es |
dc.subject | LPS | es |
dc.subject | Trehalose | es |
dc.subject | Glucose | es |
dc.subject | Glycolipids | es |
dc.subject | Medicinal chemistry | es |
dc.subject | Drug development | es |
dc.subject | Gold nanoparticles | es |
dc.subject | HEK cells | es |
dc.subject | In vivo activity | es |
dc.title | Trehalose- and Glucose-Derived Glycoamphiphiles: Small-Molecule and Nanoparticle Toll-Like Receptor 4 (TLR4) Modulators | es |
dc.type | info:eu-repo/semantics/article | es |
dcterms.identifier | https://ror.org/03yxnpp24 | |
dc.type.version | info:eu-repo/semantics/submittedVersion | es |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es |
dc.contributor.affiliation | Universidad de Sevilla. Departamento de Química Orgánica | es |
dc.relation.projectID | PRIN 2010-11 | es |
dc.relation.projectID | AF2013-44021- R | es |
dc.relation.projectID | CTQ2010 - 15848 | es |
dc.relation.projectID | FQM 1467 | es |
dc.relation.projectID | P4-176 | es |
dc.relation.projectID | J1-4170 | es |
dc.relation.publisherversion | http://dx.doi.org/10.1021/jm501182w | es |
dc.identifier.doi | 10.1021/jm501182w | es |
idus.format.extent | 68 | es |
dc.journaltitle | Journal of Medicinal Chemistry | es |
dc.publication.volumen | 57 | es |
dc.publication.issue | 21 | es |
dc.publication.initialPage | 9105 | es |
dc.publication.endPage | 9123 | es |