RT journal article
T1 Exploring the influence of the glycone space on the therapeutic potential of sp2-iminoglycolipids
A1 Padilla Pérez, M. Carmen
A1 Rodríguez Marín, Rocío
A1 González Bakker, Aday
A1 Khan, Adam N.
A1 Bastardo Torío, Mariana
A1 Padrón, José M.
A1 Martín Loro, Francisco
A1 Arroba Espinosa, Ana Isabel
A1 García-Hernández, Raquel
A1 Pérez Victoria, José M.
A1 García-Fernández, José M.
A1 Sánchez-Fernández, Elena M.
A1 Ortiz Mellet, Carmen
A2 Anatomía y Embriología Humana
K1 Iminosugars
K1 Glycolipids
K1 Cancer
K1 Apoptosis
K1 Leishmania
K1 Inflammation
K1 Inflammasome
AB Extensive structure-activity relationship studies performed on sp 2-iminoglycolipids revealed the fundamental role played by a linear dodecylsulfide/sulfonyl aglycone chain on the anticancer, antiparasitic and immunomodulatory activities. However, the influence of structural modifications within the glycone region on the therapeutic performance remains largely underexplored. To address this gap, we have designed and stereoselectively synthesized a novel series of sp 2-iminoglycolipids incorporating targeted modifications to the glycomimetic unit. These include C2 deoxygenation, bioisosteric replacement of the hydroxyl group with fluorine, and selective installation of aromatic hydrocarbons at the O3 position. Among the synthesized compounds, the f luorinated derivative (1R)-2-deoxy-1-S-dodecyl-2-fluoro-3-O-(p-fluorobenzyl)-5N,6O-oxomethylidene-1-sulfonylnojirimycin emerged as a promising multi-target candidate. Live-cell imaging in human cervical cancer (HeLa) cells revealed phenotypic markers characteristic of apoptotic cell death. Furthermore, clonogenic assays showed a significant, concentration-dependent reduction in the formation of cancer cell colonies, indicating impairment of tumor cell reproductive viability. Altogether, these data support a potent antiproliferative activity. This compound also exhibited strong antiparasitic activity, effectively inhibiting the growth of Leishmania donovani amastigotes at low micromolar concentrations. Additionally, it showed notable anti-inflammatory properties in microglial cells by downregulating the NLRP3 inflammasome signaling pathway following inf lammatory stimulation, as evidenced by reduced caspase-1 activation and suppressed IL-1β release.
PB Elsevier
SN 1768-3254
YR 2025
FD 2025-11-06
LK http://hdl.handle.net/10498/39534
UL http://hdl.handle.net/10498/39534
LA eng
DS Repositorio Institucional de la Universidad de Cádiz
RD 08-nov-2026