Publication:
Benzofuranyl-2-imidazoles as imidazoline I-2 receptor ligands for Alzheimer's disease

Simple item page
dc.contributor.authorRodriguez-Arevalo, Sergio
dc.contributor.authorBagan, Andrea
dc.contributor.authorGrinan-Ferre, Christian
dc.contributor.authorVasilopoulou, Foteini
dc.contributor.authorPallas, Merce
dc.contributor.authorBrocos-Mosquera, Iria
dc.contributor.authorCallado, Luis F
dc.contributor.authorIsabel Loza, M
dc.contributor.authorMartinez, Anton L
dc.contributor.authorBrea, Jose
dc.contributor.authorPerez, Belen
dc.contributor.authorMolins, Elies
dc.contributor.authorde Jonghe, Steven
dc.contributor.authorDaelemans, Dirk
dc.contributor.authorRadan, Milica
dc.contributor.authorDjikic, Teodora
dc.contributor.authorNikolic, Katarina
dc.contributor.authorHernández-Hernández, Elena
dc.contributor.authorGarcía-Fuster, M Julia
dc.contributor.authorGarcia-Sevilla, Jesus A
dc.contributor.authorEscolano, Carmen
dc.date.accessioned2024-09-18T06:42:19Z
dc.date.available2024-09-18T06:42:19Z
dc.date.issued2021-10-15
dc.description.abstractRecent 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.en
dc.description.sponsorshipThis work was supported by Ministerio de Ciencia, Innovacion y Universidades, Agencia Estatal de Investigacion (Spain, PID2019-107991RB-I00, PID2019-106285RB), the Basque Government (IT1211/19) and Generalitat de Catalunya (GC) (2017SGR106). The project leading to these results has received funding from la Caixa Foundation (ID 100010434) under agreement CI18-00002. This activity has received funding from the European Institute of Innovation and Technology (EIT). This body of the European Union receives support from the European Union's Horizon 2020 research and innovation programme. C.G.-F, F.V., C.E., S.R.-A., A.B., and M.P. Financial support was provided for F.V. (University of Barcelona, APIF_2017), S.R.-A. (Generalitat de Catalunya, 2018FI_B_00227), A.B. (Institute of Biomedicine UB_2018), J.A.G.-S. is a member emeritus of the Institut d'Estudis Catalans (Barcelona, Catalonia). E.H.-H. is supported by a predoctoral scholarship (FPI/2102/2018; Consejeria de Innovacion, Investigacion y Turismo del Gobierno de las Islas Baleares y del Fondo Social Europeo). M.R., T.D., and K.N. kindly acknowledge the project funded by the Ministry of Science and Technological Development of the Republic of Serbia, Contract No. 451-03-68/2020-14/200161, and HORISON 2020-COST-Action CA18133 ERNEST: European Research Network on Signal Transduction. E. M. acknowledges funding to Severo Ochoa: CEX2019917S. M.I.L, A.L.M. and J.B. gratefully acknowledge support from Xunta de Galicia (ED431C 2018/21 and ED431G 2019/02) and European Regional Development Fund (ERDF).es_ES
dc.format.page113540es_ES
dc.format.volume222es_ES
dc.identifier.citationRodriguez-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.en
dc.identifier.doi10.1016/j.ejmech.2021.113540
dc.identifier.e-issn1768-3254es_ES
dc.identifier.issn0223-5234
dc.identifier.journalEuropean Journal of Medicinal Chemistryes_ES
dc.identifier.otherhttps://hdl.handle.net/20.500.13003/19466
dc.identifier.pubmedID34118720es_ES
dc.identifier.puiL2012927091
dc.identifier.scopus2-s2.0-85111006876
dc.identifier.urihttps://hdl.handle.net/20.500.12105/23190
dc.identifier.wos685593800001
dc.language.isoengen
dc.publisherElsevier
dc.relation.publisherversionhttps://dx.doi.org/10.1016/j.ejmech.2021.113540en
dc.rights.accessRightsopen accessen
dc.rights.licenseAttribution 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectImidazoline I-2 receptors
dc.subjectImidazoline I-2 receptor ligands
dc.subjectNeuroprotection
dc.subject5xFAD
dc.subjectBenzofuranyl-2-imidazoles
dc.subjectOxidative stress
dc.subject.decsAnimales*
dc.subject.decsLínea Celular Tumoral*
dc.subject.decsImidazoles*
dc.subject.decsLigandos*
dc.subject.decsApoptosis*
dc.subject.decsRelación Estructura-Actividad*
dc.subject.decsMasculino*
dc.subject.decsReceptores de Imidazolina*
dc.subject.decsBenzofuranos*
dc.subject.decsRelación Dosis-Respuesta a Droga*
dc.subject.decsHumanos*
dc.subject.decsEnfermedad de Alzheimer*
dc.subject.decsEstrés Oxidativo*
dc.subject.decsRatones*
dc.subject.decsEstructura Molecular*
dc.subject.meshOxidative Stress*
dc.subject.meshAlzheimer Disease*
dc.subject.meshDose-Response Relationship, Drug*
dc.subject.meshMolecular Structure*
dc.subject.meshBenzofurans*
dc.subject.meshHumans*
dc.subject.meshCell Line, Tumor*
dc.subject.meshLigands*
dc.subject.meshMale*
dc.subject.meshApoptosis*
dc.subject.meshStructure-Activity Relationship*
dc.subject.meshAnimals*
dc.subject.meshImidazoles*
dc.subject.meshImidazoline Receptors*
dc.subject.meshMice*
dc.titleBenzofuranyl-2-imidazoles as imidazoline I-2 receptor ligands for Alzheimer's diseaseen
dc.typeresearch articleen
dspace.entity.typePublication
relation.isPublisherOfPublication7d471502-7bd5-4f7a-90a4-8274382509ef
relation.isPublisherOfPublication.latestForDiscovery7d471502-7bd5-4f7a-90a4-8274382509ef

Files

Collections

IdisBa - Instituto de Investigación Sanitaria Illes Balears (Baleares)