{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T11:35:38Z","timestamp":1769945738274,"version":"3.49.0"},"reference-count":53,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2021,10,3]],"date-time":"2021-10-03T00:00:00Z","timestamp":1633219200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003407","name":"Ministero dell\u2019Istruzione, dell\u2019Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","award":["2017SNRXH3"],"award-info":[{"award-number":["2017SNRXH3"]}],"id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["UID\/QUI\/00100\/2019"],"award-info":[{"award-number":["UID\/QUI\/00100\/2019"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000921","name":"European Cooperation in Science and Technology","doi-asserted-by":"publisher","award":["CA18202"],"award-info":[{"award-number":["CA18202"]}],"id":[{"id":"10.13039\/501100000921","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) is a severe multifactorial neurodegenerative disorder characterized by a progressive loss of neurons in the brain. Despite research efforts, the pathogenesis and mechanism of AD progression are not yet completely understood. There are only a few symptomatic drugs approved for the treatment of AD. The multifactorial character of AD suggests that it is important to develop molecules able to target the numerous pathological mechanisms associated with the disease. Thus, in the context of the worldwide recognized interest of multifunctional ligand therapy, we report herein the synthesis, characterization, physicochemical and biological evaluation of a set of five (1a\u2013e) new ferulic acid-based hybrid compounds, namely feroyl-benzyloxyamidic derivatives enclosing different substituent groups, as potential anti-Alzheimer\u2019s disease agents. These hybrids can keep both the radical scavenging activity and metal chelation capacity of the naturally occurring ferulic acid scaffold, presenting also good\/mild capacity for inhibition of self-A\u03b2 aggregation and fairly good inhibition of Cu-induced A\u03b2 aggregation. The predicted pharmacokinetic properties point towards good absorption, comparable to known oral drugs.<\/jats:p>","DOI":"10.3390\/molecules26196015","type":"journal-article","created":{"date-parts":[[2021,10,8]],"date-time":"2021-10-08T21:23:55Z","timestamp":1633728235000},"page":"6015","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Multifunctional Small Molecules as Potential Anti-Alzheimer\u2019s Disease Agents"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6933-7478","authenticated-orcid":false,"given":"Beatrice","family":"Bargagna","sequence":"first","affiliation":[{"name":"Department of Earth Sciences, University of Pisa, Via Santa Maria 53-55, 56100 Pisa, Italy"},{"name":"Centro de Qu\u00edmica Estrutural and Departamento de Engenharia Qu\u00edmica, Instituto Superior T\u00e9cnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2762-1929","authenticated-orcid":false,"given":"Lidia","family":"Ciccone","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Pisa, Via Bonanno 6, 56126 Pisa, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3547-7277","authenticated-orcid":false,"given":"Susanna","family":"Nencetti","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Pisa, Via Bonanno 6, 56126 Pisa, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4069-9368","authenticated-orcid":false,"given":"M. Am\u00e9lia","family":"Santos","sequence":"additional","affiliation":[{"name":"Centro de Qu\u00edmica Estrutural and Departamento de Engenharia Qu\u00edmica, Instituto Superior T\u00e9cnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8554-4992","authenticated-orcid":false,"given":"S\u00edlvia","family":"Chaves","sequence":"additional","affiliation":[{"name":"Centro de Qu\u00edmica Estrutural and Departamento de Engenharia Qu\u00edmica, Instituto Superior T\u00e9cnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8676-7311","authenticated-orcid":false,"given":"Caterina","family":"Camodeca","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Pisa, Via Bonanno 6, 56126 Pisa, Italy"}]},{"given":"Elisabetta","family":"Orlandini","sequence":"additional","affiliation":[{"name":"Department of Earth Sciences, University of Pisa, Via Santa Maria 53-55, 56100 Pisa, Italy"},{"name":"Research Center \u201cE. Piaggio\u201d, University of Pisa, 56122 Pisa, Italy"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Alzheimer\u2019s Association (2019). 2019 Alzheimer\u2019s Disease Facts and Figures. Alzheimer Dement., 15, 321\u2013387.","DOI":"10.1016\/j.jalz.2019.01.010"},{"key":"ref_2","unstructured":"(2021, February 26). Alzheimer\u2019s Disease International World Alzheimer Report 2019. Available online: https:\/\/www.alz.co.uk\/research\/WorldAlzheimerReport2019.pdf."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1038\/nrn2967","article-title":"Amyloid-\u03b2 and Tau\u2014A toxic pas de deux in Alzheimer\u2019s disease","volume":"12","author":"Ittner","year":"2011","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_4","unstructured":"(2021, March 30). Frontiers in Clinical Drug Research\u2014Alzheimer Disorders. 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