2026-07-21T14:26:58Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/231902024-11-29T02:00:51Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16967

00925njm 22002777a 4500 dc Rodriguez-Arevalo, Sergio author Bagan, Andrea author Grinan-Ferre, Christian author Vasilopoulou, Foteini author Pallas, Merce author Brocos-Mosquera, Iria author Callado, Luis F author Isabel Loza, M author Martinez, Anton L author Brea, Jose author Perez, Belen author Molins, Elies author de Jonghe, Steven author Daelemans, Dirk author Radan, Milica author Djikic, Teodora author Nikolic, Katarina author Hernández-Hernández, Elena author García-Fuster, M Julia author Garcia-Sevilla, Jesus A author Escolano, Carmen author 2021-10-15 Recent findings unveil the pharmacological modulation of imidazoline I-2 receptors (I-2-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 I-2-IR and most of them have been predicted to be brain permeable. Acute treatment in mice with 2-(2-benzofuranyl)-2imidazole, 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. (C) 2021 Elsevier Masson SAS. All rights reserved. Rodriguez-Arevalo S, Bagan A, Grinan-Ferre C, Vasilopoulou F, Pallas M, Brocos-Mosquera I, et al. Benzofuranyl-2-imidazoles as imidazoline I-2 receptor ligands for Alzheimer's disease. Eur J Med Chem. 2021 Oct 15;222:113540. 10.1016/j.ejmech.2021.113540 1768-3254 0223-5234 European Journal of Medicinal Chemistry https://hdl.handle.net/20.500.13003/19466 34118720 L2012927091 2-s2.0-85111006876 https://hdl.handle.net/20.500.12105/23190 685593800001 Imidazoline I-2 receptors Imidazoline I-2 receptor ligands Neuroprotection 5xFAD Benzofuranyl-2-imidazoles Oxidative stress Benzofuranyl-2-imidazoles as imidazoline I-2 receptor ligands for Alzheimer's disease