{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T20:50:08Z","timestamp":1769287808890,"version":"3.49.0"},"reference-count":36,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T00:00:00Z","timestamp":1769040000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100014810","name":"Fondazione di Sardegna","doi-asserted-by":"publisher","award":["F73C23001850007"],"award-info":[{"award-number":["F73C23001850007"]}],"id":[{"id":"10.13039\/100014810","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Xunta da Galicia Grant","award":["ED431B 2025\/15"],"award-info":[{"award-number":["ED431B 2025\/15"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>New arylbenzofuran derivatives were designed, synthesized, and evaluated as potential inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Five hybrid compounds (31\u201335) feature a 2-phenylbenzofuran core linked via a heptyloxy spacer to an N-methylbenzylamine moiety, to enhance interactions within the active site of BChE. Biological evaluation revealed that brominated derivatives 34 and 35 showed the highest cholinesterases (ChE) inhibition compared to their chlorinated analogs, with compound 34 showing the highest activity for both AChE (IC50 = 27.7 \u03bcM) and BChE (IC50 = 0.7 \u03bcM). These compounds proved to be non-cytotoxic and demonstrated significant antioxidant activity in SH-SY5Y cells exposed to hydrogen peroxide (H2O2), highlighting their potential to mitigate oxidative stress: a key pathological factor in Alzheimer\u2019s disease. Structural activity analysis suggests that bromine substitution at position 7 and the presence of a seven-carbon linker are critical for dual ChE inhibition and selectivity towards BChE. ADMET prediction indicates favorable pharmacokinetic properties, including drug-likeness and oral bioavailability. Overall, these findings highlight the potential of the 2-arylbenzofuran as a promising scaffold for multitarget-directed ligands in Alzheimer\u2019s disease therapy.<\/jats:p>","DOI":"10.3390\/biom16010178","type":"journal-article","created":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T10:41:34Z","timestamp":1769164894000},"page":"178","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["2-Arylbenzofurans as Selective Cholinesterase Inhibitors: Design, Synthesis, and Evaluation as Alzheimer\u2019s Disease Agents"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0307-1544","authenticated-orcid":false,"given":"Giovanna Lucia","family":"Delogu","sequence":"first","affiliation":[{"name":"Department of Live and Environmental Sciences, University of Cagliari, Cittadella Universitaria, SS 554, Km 4.5, 09042 Monserrato, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8213-2335","authenticated-orcid":false,"given":"Michela","family":"Begala","sequence":"additional","affiliation":[{"name":"Department of Live and Environmental Sciences, University of Cagliari, Cittadella Universitaria, SS 554, Km 4.5, 09042 Monserrato, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-4678-1339","authenticated-orcid":false,"given":"Manuel","family":"Nov\u00e1s","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica Org\u00e1nica, Facultad de Farmacia, Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain"},{"name":"BioFarma Research Group, Center for Research in Molecular Medicine and Chronic Diseases (CiMUS), University of Santiago de Compostela, 15782 Santiago de Compostela, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3470-8299","authenticated-orcid":false,"given":"Maria Jo\u00e3o","family":"Matos","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica Org\u00e1nica, Facultad de Farmacia, Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9010-1926","authenticated-orcid":false,"given":"Franca","family":"Piras","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science, University of Cagliari, Cittadella Universitaria, SS 554, Km 4.5, 09042 Monserrato, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sonia","family":"Floris","sequence":"additional","affiliation":[{"name":"Department of Live and Environmental Sciences, University of Cagliari, Cittadella Universitaria, SS 554, Km 4.5, 09042 Monserrato, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2350-7966","authenticated-orcid":false,"given":"Francesca","family":"Pintus","sequence":"additional","affiliation":[{"name":"Department of Live and Environmental Sciences, University of Cagliari, Cittadella Universitaria, SS 554, Km 4.5, 09042 Monserrato, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8499-5265","authenticated-orcid":false,"given":"Michele","family":"Mancinelli","sequence":"additional","affiliation":[{"name":"Department of Industrial Chemistry \u201cToso Montanari\u201d, University of Bologna, Viale del Risorgimento, 4, 40136 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4154-9740","authenticated-orcid":false,"given":"Benedetta","family":"Era","sequence":"additional","affiliation":[{"name":"Department of Live and Environmental Sciences, University of Cagliari, Cittadella Universitaria, SS 554, Km 4.5, 09042 Monserrato, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3009-4226","authenticated-orcid":false,"given":"Antonella","family":"Fais","sequence":"additional","affiliation":[{"name":"Department of Live and Environmental Sciences, University of Cagliari, Cittadella Universitaria, SS 554, Km 4.5, 09042 Monserrato, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1021\/jm7009364","article-title":"Multi-target-Directed Ligands to Combat Neurodegenerative Diseases","volume":"51","author":"Cavalli","year":"2008","journal-title":"J. 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