%0 Journal Article
%A Sanchez-Fernandez, Elena M.
%A Garcia-Hernandez, Raquel
%A Gamarro, Francisco
%A Arroba, Ana I.
%A Aguilar-Diosdado, Manuel
%A Padron, Jose M.
%A Garcia Fernandez, Jose M.
%A Ortiz Mellet, Carmen
%T Synthesis of sp(2)-Iminosugar Selenoglycolipids as Multitarget Drug Candidates with Antiproliferative, Leishmanicidal and Anti-Inflammatory Properties
%D 2021
%U https://hdl.handle.net/10668/25219
%X sp(2)-Iminosugar glycolipids (sp(2)-IGLs) represent a consolidated family of glycoconjugate mimetics encompassing a monosaccharide-like glycone moiety with a pseudoamide-type nitrogen replacing the endocyclic oxygen atom of carbohydrates and an axially-oriented lipid chain anchored at the pseudoanomeric position. The combination of these structural features makes them promising candidates for the treatment of a variety of conditions, spanning from cancer and inflammatory disorders to parasite infections. The exacerbated anomeric effect associated to the putative sp(2)-hybridized N-atom imparts chemical and enzymatic stability to sp(2)-IGLs and warrants total alpha-anomeric stereoselectivity in the key glycoconjugation step. A variety of O-, N-, C- and S-pseudoglycosides, differing in glycone configurational patterns and lipid nature, have been previously prepared and evaluated. Here we expand the chemical space of sp(2)-IGLs by reporting the synthesis of alpha-d-gluco-configured analogs with a bicyclic (5N,6O-oxomethylidene)nojirimycin (ONJ) core incorporating selenium at the glycosidic position. Structure-activity relationship studies in three different scenarios, namely cancer, Leishmaniasis and inflammation, convey that the therapeutic potential of the sp(2)-IGLs is highly dependent, not only on the length of the lipid chain (linear aliphatic C-12 vs. C-8), but also on the nature of the glycosidic atom (nitrogen vs. sulfur vs. selenium). The ensemble of results highlights the alpha-dodecylseleno-ONJ-glycoside as a promising multitarget drug candidate.
%K seleno-sp(2)-iminoglycolipids
%K multitarget
%K immunomodulation
%K cancer
%K Leishmania
%K inflammation
%K Stereoselective-synthesis
%K Organoselenium compounds
%K Derivatives
%K Modulation
%K Chemistry
%K Ligands
%K Lectins
%K Mimics
%K Ureas
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