Carregant...
Fitxers
Tipus de document
ArticleVersió
Versió acceptadaData de publicació
Tots els drets reservats
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/178725
Benzofuranyl-2-imidazoles as imidazoline I2 receptor ligands for Alzheimer's disease
Títol de la revista
Director/Tutor
ISSN de la revista
Títol del volum
Recurs relacionat
Resum
Recent findings unveil the pharmacological modulation of imidazoline I2 receptors (I2-IR) as a novel strategy to face unmet medical neurodegenerative diseases. In this work, we report the chemical characterization, three-dimensional quantitative structure-activity relationship (3D-QSAR) and ADMET in silico of a family of benzofuranyl-2-imidazoles that exhibit affinity against human brain I2-IR and most of them have been predicted to be brain permeable. Acute treatment in mice with 2-(2-benzofuranyl)-2- imidazole, known as LSL60101 (garsevil), showed non-warning properties in the ADMET studies and an optimal pharmacokinetic profile. Moreover, LSL60101 induced hypothermia in mice while decreased pro-apoptotic FADD protein in the hippocampus. In vivo studies in the familial Alzheimer's disease 5xFAD murine model with the representative compound, revealed significant decreases in the protein expression levels of antioxidant enzymes superoxide dismutase and glutathione peroxidase in hippocampus. Overall, LSL60101 plays a neuroprotective role by reducing apoptosis and modulating oxidative stress.
Matèries (anglès)
Citació
Citació
RODRÍGUEZ-ARÉVALO, Sergio, BAGAN POLONIO, Andrea, GRIÑÁN FERRÉ, Christian, VASILOPOULOU, Foteini, PALLÀS I LLIBERÍA, Mercè, BROCOS-MOSQUERA, Iria, CALLADO, Luis f., LOZA, María isabel, MARTÍNEZ, Antón l., BREA, José, PÉREZ, Belén, MOLINS I GRAU, Elies, JONGHE, Steven de, DAELEMANS, Dirk, RADAN, Milica, DJIKIC, Teodora, NIKOLIC, Katarina, HERNÁNDEZ-HERNÁNDEZ, Elena, GARCÍA-FUSTER, M. julia, GARCÍA-SEVILLA, Jesús a., ESCOLANO MIRÓN, Carmen. Benzofuranyl-2-imidazoles as imidazoline I2 receptor ligands for Alzheimer's disease. _European Journal of Medicinal Chemistry_. 2021. Vol. 222, núm. 113540. [consulta: 25 de gener de 2026]. ISSN: 0223-5234. [Disponible a: https://hdl.handle.net/2445/178725]