Rodríguez Arévalo, SergioBagán, AndreaGriñán Ferré, ChristianVasilopoulou, FoteiniPallàs, MercèBrocos Mosquera, IriaCallado, Luis F.Loza García, María IsabelMartínez Rodríguez, Antón LeandroBrea Floriani, José ManuelPérez, BelénMolins, EliesDe Jonghe, StevenDaelemans, DirkRadan, MilicaDjikic, TeodoraNikolic, KatarinaHernández Hernández, ElenaGarcía Fuster, M. JuliaGarcía Sevilla, Jesús A.Escolano, Carmen2026-01-132026-01-132021-05-20Sergio Rodriguez-Arévalo, Andrea Bagán, Christian Griñán-Ferré, Foteini Vasilopoulou, Mercè Pallàs, Iria Brocos-Mosquera, Luis F. Callado, M. Isabel Loza, Antón L. Martínez, José Brea, Belén Pérez, Elies Molins, Steven De Jonghe, Dirk Daelemans, Milica Radan, Teodora Djikic, Katarina Nikolic, Elena Hernández-Hernández, M. Julia García-Fuster, Jesús A. García-Sevilla, Carmen Escolano, Benzofuranyl-2-imidazoles as imidazoline I2 receptor ligands for Alzheimer's disease, European Journal of Medicinal Chemistry, Volume 222, 2021, 113540, ISSN 0223-5234, https://doi.org/10.1016/j.ejmech.2021.113540https://hdl.handle.net/10347/45060Recent 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 stresseng© 2021 The Authors. Published by Elsevier Masson SAS. This is an open access article distributed under the terms of the Creative Commons CC-BY licenseAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/Imidazoline I2 receptorsImidazoline I2 receptor ligandsNeuroprotection5xFADBenzofuranyl-2-imidazolesOxidative stressjournal article10.1016/j.ejmech.2021.1135401768-3254open access