{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T02:44:22Z","timestamp":1785725062317,"version":"3.56.0"},"reference-count":81,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004901","name":"Minas Gerais State Research Support Foundation","doi-asserted-by":"publisher","award":["APQ-04559-22"],"award-info":[{"award-number":["APQ-04559-22"]}],"id":[{"id":"10.13039\/501100004901","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004901","name":"Deep Tech","doi-asserted-by":"publisher","award":["APQ-07852-25"],"award-info":[{"award-number":["APQ-07852-25"]}],"id":[{"id":"10.13039\/501100004901","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004901","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de Minas Gerais","doi-asserted-by":"publisher","award":["APQ-03224-24"],"award-info":[{"award-number":["APQ-03224-24"]}],"id":[{"id":"10.13039\/501100004901","id-type":"DOI","asserted-by":"publisher"}]},{"award":["APQ-03224-24"],"award-info":[{"award-number":["APQ-03224-24"]}],"id":[{"id":"https:\/\/ror.org\/00nc55f03","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["305452\/2025-8"],"award-info":[{"award-number":["305452\/2025-8"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"award":["305452\/2025-8"],"award-info":[{"award-number":["305452\/2025-8"]}],"id":[{"id":"https:\/\/ror.org\/03swz6y49","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: Alzheimer\u2019s disease (AD) is a progressive, multifactorial neurodegenerative condition characterized by neurofibrillary tangles, neuronal loss, cognitive impairment, and accumulation of \u03b2-amyloid plaques. Considering the limitations of current treatments, which present adverse effects and only alleviate symptoms without modifying disease progression, there is an urgent need for new therapeutic approaches. This study aimed to investigate the neuroprotective potential of synthetic derivatives of (1E,4E)-1,5-bis[(het)aryl]penta-1,4-dien-3-ones, focusing on the inhibition of the cholinesterase enzymes acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), targets directly related to the cholinergic deficit observed in AD. Methods: The compounds were initially synthesized by aldol condensation reactions, with subsequent physicochemical characterization. They were then subjected to in silico assays that demonstrated high binding affinity to the active sites of AChE and BChE. The derivatives were evaluated in vitro for their inhibitory activity on these enzymes and in vivo in an experimental model of AD induced by streptozotocin in Wistar rats. Results: The synthesized derivatives showed favorable predicted interactions with the active sites of AChE and BChE, supporting their potential as cholinesterase inhibitors. In vitro assays demonstrated inhibitory activity against both enzymes, with selected derivatives showing improved activity compared with the parent scaffold. In the in vivo model, treatment with the selected compounds was associated with neuroprotective effects, suggesting preservation of nervous tissue integrity under AD-like conditions. Conclusions: These findings indicate that derivatives may represent promising candidates for further investigation as multitarget agents for AD. The study reinforces the relevance of integrating organic synthesis, molecular modeling, enzymatic assays, and in vivo evaluation in the search for new therapeutic strategies for neurodegenerative diseases.<\/jats:p>","DOI":"10.3390\/ph19081216","type":"journal-article","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T01:43:27Z","timestamp":1785721407000},"page":"1216","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Design, Synthesis, In Vitro and In Vivo Evaluation of Novel Anti-Alzheimer\u2019s (1E,4E)-1,5-Bis[(het)aryl]penta-1,4-dien-3-one Derivatives"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-4543-3144","authenticated-orcid":false,"given":"G\u00e9ssica Oliveira","family":"Mendes","sequence":"first","affiliation":[{"name":"Graduate Program in Biotechnology, State University of Feira de Santana, Feira de Santana 44036-900, BA, Brazil"},{"name":"Laboratory of Cheminformatics and Biological Evaluation, Department of Health, State University of Feira de Santana, Feira de Santana 44036-900, BA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas Diego Pereira","family":"Bento","sequence":"additional","affiliation":[{"name":"Department of Natural Sciences, Federal University of S\u00e3o Jo\u00e3o del-Rei, S\u00e3o Jo\u00e3o del-Rei 36301-160, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-9577-2577","authenticated-orcid":false,"given":"Thiago Malverde de","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Department of Medicine, Federal University of S\u00e3o Jo\u00e3o del-Rei, Pra\u00e7a Dom Helv\u00e9cio, 74, Dom Bosco, Minas Gerais, S\u00e3o Jo\u00e3o del-Rei 36301-160, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2089-4403","authenticated-orcid":false,"given":"Deyse Brito","family":"Barbosa","sequence":"additional","affiliation":[{"name":"Graduate Program in Biotechnology, State University of Feira de Santana, Feira de Santana 44036-900, BA, Brazil"},{"name":"Laboratory of Cheminformatics and Biological Evaluation, Department of Health, State University of Feira de Santana, Feira de Santana 44036-900, BA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guilherme Saraiva","family":"Tsui","sequence":"additional","affiliation":[{"name":"Department of Medicine, Federal University of S\u00e3o Jo\u00e3o del-Rei, Pra\u00e7a Dom Helv\u00e9cio, 74, Dom Bosco, Minas Gerais, S\u00e3o Jo\u00e3o del-Rei 36301-160, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen Nunes","family":"Gomes","sequence":"additional","affiliation":[{"name":"Department of Medicine, Federal University of S\u00e3o Jo\u00e3o del-Rei, Pra\u00e7a Dom Helv\u00e9cio, 74, Dom Bosco, Minas Gerais, S\u00e3o Jo\u00e3o del-Rei 36301-160, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raphaela Oliveira","family":"Sales","sequence":"additional","affiliation":[{"name":"Department of Medicine, Federal University of S\u00e3o Jo\u00e3o del-Rei, Pra\u00e7a Dom Helv\u00e9cio, 74, Dom Bosco, Minas Gerais, S\u00e3o Jo\u00e3o del-Rei 36301-160, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mateus Silva de Castro","family":"Rocha","sequence":"additional","affiliation":[{"name":"Department of Medicine, Federal University of S\u00e3o Jo\u00e3o del-Rei, Pra\u00e7a Dom Helv\u00e9cio, 74, Dom Bosco, Minas Gerais, S\u00e3o Jo\u00e3o del-Rei 36301-160, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1343-1331","authenticated-orcid":false,"given":"Michel Pires 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Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/j.cger.2014.04.001","article-title":"Dementia and Cognitive Impairment: Epidemiology, Diagnosis and Treatment","volume":"30","author":"Hugo","year":"2014","journal-title":"Clin. 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