{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:56:33Z","timestamp":1760151393708,"version":"build-2065373602"},"reference-count":25,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,3,2]],"date-time":"2022-03-02T00:00:00Z","timestamp":1646179200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>In the present work, we use a merger of computational and biochemical techniques as a rational guideline for structural modification of benzofuran derivatives to find pertinent structural features for the butyrylcholinesterase inhibitory activity and selectivity. Previously, we revealed a series of 2-phenylbenzofuran compounds that displayed a selective inhibitory activity for BChE. Here, in an effort to discover novel selective BChE inhibitors with favorable physicochemical and pharmacokinetic profiles, 2-benzylbenzofurans were designed, synthesized, and evaluated as BChE inhibitors. The 2-phenylbenzofuran scaffold structure is modified by introducing one methylene spacer between the benzofuran core and the 2-phenyl ring with a hydroxyl substituent in the para or meta position. Either position 5 or 7 of the benzofuran scaffold was substituted with a bromine or chlorine atom. Further assessment of the selected list of compounds indicated that the substituent\u2019s nature and position determined their activity and selectivity. 5-bromo-2-(4-hydroxybenzyl)benzofuran 9B proved to be the most potent butyrylcholinesterase inhibitor (IC50 = 2.93 \u00b5M) of the studied series. Computational studies were carried out to correlate the theoretical and experimental binding affinity of the compounds to the BChE protein.<\/jats:p>","DOI":"10.3390\/ph15030304","type":"journal-article","created":{"date-parts":[[2022,3,2]],"date-time":"2022-03-02T22:53:25Z","timestamp":1646261605000},"page":"304","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Structural Insight of New Butyrylcholinesterase Inhibitors Based on Benzylbenzofuran Scaffold"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0307-1544","authenticated-orcid":false,"given":"Giovanna L.","family":"Delogu","sequence":"first","affiliation":[{"name":"Department of Life and Environmental Sciences, University of Cagliari, Monserrato, 09042 Cagliari, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3009-4226","authenticated-orcid":false,"given":"Antonella","family":"Fais","sequence":"additional","affiliation":[{"name":"Department of Life and Environmental Sciences, University of Cagliari, Monserrato, 09042 Cagliari, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2350-7966","authenticated-orcid":false,"given":"Francesca","family":"Pintus","sequence":"additional","affiliation":[{"name":"Department of Life and Environmental Sciences, University of Cagliari, Monserrato, 09042 Cagliari, Italy"}]},{"given":"Chinmayi","family":"Goyal","sequence":"additional","affiliation":[{"name":"Yorktown High School, 2727 Crompond Road, Yorktown Heights, NY 10598, USA"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3470-8299","authenticated-orcid":false,"given":"Maria J.","family":"Matos","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00ecmica Org\u00e0nica, Facultade de Farmacia, Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4154-9740","authenticated-orcid":false,"given":"Benedetta","family":"Era","sequence":"additional","affiliation":[{"name":"Department of Life and Environmental Sciences, University of Cagliari, Monserrato, 09042 Cagliari, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2547-0071","authenticated-orcid":false,"given":"Amit","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Electrical and Electronic Engineering, University of Cagliari, Via Marengo 2, 09123 Cagliari, Italy"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1038\/nrd1549","article-title":"Docking and scoring in virtual screening for drug discovery: Methods and applications","volume":"3","author":"Kitchen","year":"2004","journal-title":"Nat. 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