RT Journal Article
T1 Synthesis of sp(2)-Iminosugar Selenoglycolipids as Multitarget Drug Candidates with Antiproliferative, Leishmanicidal and Anti-Inflammatory Properties
A1 Sanchez-Fernandez, Elena M.
A1 Garcia-Hernandez, Raquel
A1 Gamarro, Francisco
A1 Arroba, Ana I.
A1 Aguilar-Diosdado, Manuel
A1 Padron, Jose M.
A1 Garcia Fernandez, Jose M.
A1 Ortiz Mellet, Carmen
K1 seleno-sp(2)-iminoglycolipids
K1 multitarget
K1 immunomodulation
K1 cancer
K1 Leishmania
K1 inflammation
K1 Stereoselective-synthesis
K1 Organoselenium compounds
K1 Derivatives
K1 Modulation
K1 Chemistry
K1 Ligands
K1 Lectins
K1 Mimics
K1 Ureas
AB 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.
PB Mdpi
YR 2021
FD 2021-12-01
LK https://hdl.handle.net/10668/25219
UL https://hdl.handle.net/10668/25219
LA en
DS RISalud
RD Apr 7, 2025