2026-07-21T14:27:02Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/231902024-11-29T02:00:51Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16967
Repisalud
author
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
2024-09-18T06:42:19Z
2024-09-18T06:42:19Z
2021-10-15
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
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.
eng
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
research article