RT info:eu-repo/semantics/article
T1 Fluoro-labelled sp2-iminoglycolipids with immunomodulatory properties
A1 M. Carmen Padilla-P´érez
A1 Elena M. S´anchez-Fern´ández
A1 Aday Gonz´alez-Bakker
A1 González Bakker, Aday
A1 Adri´an Puerta
A1 Padrón Carrillo, José Manuel
A1 Francisco Martín-Loro
A1 Ana I. Arroba
A1 Jos´é Manuel García Fern´andez
A1 Carmen Ortiz Mellet
A2 Química Orgánica
A2 Grupo BioLab
Instituto Universitario de Bio-Orgánica Antonio González
K1 Fluorinated glycomimetics
K1 Selectfluor
K1 Immunomodulation
K1 Cancer
K1 Inflammation
K1 p38α MAPK
AB 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 carbohydrates, 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 glycolipid 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 autoactivation under an inflammatory context.
YR 2023
FD 2023
LK http://riull.ull.es/xmlui/handle/915/40747
UL http://riull.ull.es/xmlui/handle/915/40747
LA Inglés
DS Repositorio institucional de la Universidad de La Laguna
RD 26-abr-2025