dc.creator | Padilla Pérez, María del Carmen | es |
dc.creator | Sánchez Fernández, Elena Matilde | es |
dc.creator | González-Bakker, Aday | es |
dc.creator | Puerta, Adrián | es |
dc.creator | Padrón, José M. | es |
dc.creator | Martín-Loro, Francisco | es |
dc.creator | García Fernández, José Manuel | es |
dc.creator | Ortiz Mellet, Carmen | es |
dc.date.accessioned | 2023-05-10T08:22:57Z | |
dc.date.available | 2023-05-10T08:22:57Z | |
dc.date.issued | 2023 | |
dc.identifier.citation | Padilla Pérez, M.d.C., Sánchez Fernández, E.M., González-Bakker, A., Puerta, A., Padrón, J.M., Martín-Loro, F.,...,Ortiz Mellet, C. (2023). Fluoro-labelled sp2-iminoglycolipids with immunomodulatory properties. European Journal of Medicinal Chemistry, 255, 115390. https://doi.org/10.1016/j.ejmech.2023.115390. | |
dc.identifier.issn | 0223-5234 | es |
dc.identifier.uri | https://hdl.handle.net/11441/145750 | |
dc.description.abstract | The unique electronic properties of the fluorine atom make its strategic incorporation into a bioactive compound
a very useful tool in the design of drugs with optimized pharmacological properties. In the field of the carbo-
hydrates, its selective installation at C2 position has proven particularly interesting, some 2-deoxy-2-fluorosugar
derivatives being currently in the market. We have now transferred this feature into immunoregulatory glyco-
lipid mimetics that contain a sp2-iminosugar moiety, namely sp2-iminoglycolipids (sp2-IGLs). The synthesis of
two epimeric series of 2-deoxy-2-fluoro-sp2-IGLs, structurally related to nojirimycin and mannonojirimycin, has
been accomplished by sequential Selectfluor-mediated fluorination and thioglycosidation of sp2-iminoglycals.
Exclusively the α-anomer is obtained regardless of the configurational profile of the sp2-IGL (D-gluco or D-manno),
highlighting the overwhelming anomeric effect in these prototypes. Notably, the combination of a fluorine atom
at C2 and an α-oriented sulfonyl dodecyl lipid moiety in compound 11 led to remarkable anti-proliferative
properties, featuring similar GI50 values than the chemotherapy drug Cisplatin against several tumor cell lines
and better selectivity. The biochemical data further evidence a strong reduction of the number of tumor cell
colonies and apoptosis induction. Mechanistic investigations revealed that this fluoro-sp2-IGL induces the non-
canonical activation mode of the mitogen-activated protein kinase signaling pathway, causing p38α autoacti-
vation under an inflammatory context. | es |
dc.description.sponsorship | VII Plan Propio de Investigación y Transferencia de la Universidad de Sevilla - VIIPPIT-2022-V.1 | es |
dc.description.sponsorship | Junta de Andalucía y Fondos Europeos de Desarrollo Regional -P20_00166 | es |
dc.description.sponsorship | Ministerio de Ciencia e Innovación, Agencia Estatal de Investigación, de España y Fondos Europeos de Desarrollo Regional - PID2019-105858RB-I00, RTI2018-097609-B-C21, PID2021-124247OB-C21 y PID2021-123059OB-I00 | es |
dc.description.sponsorship | Instituto de Salud Carlos III - PI22/01718 | es |
dc.description.sponsorship | Consejería de Universidad, Investigación e Innovación de la Junta de Andalucía - PI20-01331 | es |
dc.description.sponsorship | Agencia Canaria de Investigación Innovación d Sociedad de la Información del Gobierno canario (ACIISI) - TESIS2020010055 | es |
dc.format | application/pdf | es |
dc.format.extent | 19 p. | es |
dc.language.iso | eng | es |
dc.publisher | Elsevier | es |
dc.relation.ispartof | European Journal of Medicinal Chemistry, 255, 115390. | |
dc.rights | Atribución 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.subject | Fluorinated glycomimetics | es |
dc.subject | Selectfluor | es |
dc.subject | Immunomodulation | es |
dc.subject | Cancer | es |
dc.subject | Inflammation | es |
dc.subject | p38α MAPK | es |
dc.title | Fluoro-labelled sp2-iminoglycolipids with immunomodulatory properties | es |
dc.type | info:eu-repo/semantics/article | es |
dc.type.version | info:eu-repo/semantics/publishedVersion | es |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es |
dc.contributor.affiliation | Universidad de Sevilla. Departamento de Química orgánica | es |
dc.relation.projectID | PID2019-105858RB-I00 | es |
dc.relation.projectID | RTI2018-097609-B-C21 | es |
dc.relation.projectID | PID2021-124247OB-C21 | es |
dc.relation.projectID | PID2021-123059OB-I00 | es |
dc.relation.projectID | P20_00166 | es |
dc.relation.projectID | PI22/01718 | es |
dc.relation.projectID | PI20-01331 | es |
dc.relation.projectID | ACIISI/TESIS2020010055 | es |
dc.relation.projectID | PI20-0036 | es |
dc.relation.publisherversion | https://doi.org/10.1016/j.ejmech.2023.115390 | es |
dc.identifier.doi | 10.1016/j.ejmech.2023.115390 | es |
dc.journaltitle | European Journal of Medicinal Chemistry | es |
dc.publication.volumen | 255 | es |
dc.publication.initialPage | 115390 | es |
dc.contributor.funder | Ministerio de Ciencia e Innovación (MICIN). España | es |
dc.contributor.funder | Agencia Estatal de Investigación. España | es |
dc.contributor.funder | European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER) | es |
dc.contributor.funder | Universidad de Sevilla | es |
dc.contributor.funder | Instituto de Salud Carlos III | es |
dc.contributor.funder | Junta de Andalucía | es |
dc.contributor.funder | Gobierno de Canarias. España | es |