{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T13:08:38Z","timestamp":1768568918379,"version":"3.49.0"},"reference-count":58,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,1,15]],"date-time":"2021-01-15T00:00:00Z","timestamp":1610668800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Portuguese Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia (FCT)","award":["UID\/QUI\/00100\/2019"],"award-info":[{"award-number":["UID\/QUI\/00100\/2019"]}]},{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia (FCT)","award":["POCI-01-0145-FEDER-030712"],"award-info":[{"award-number":["POCI-01-0145-FEDER-030712"]}]},{"name":"University of Bari \u201cAldo Moro\u201d","award":["Contributo ordinario di supporto alla ricerca 2017-18 (Luca Piemontese)"],"award-info":[{"award-number":["Contributo ordinario di supporto alla ricerca 2017-18 (Luca Piemontese)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) is generally recognized as a multifactorial neurodegenerative pathology with an increasing impact on society. Tenuazonic acid (TA) is a natural compound that was recently identified as a potential multitarget ligand with anti-cholinesterase, anti-amyloidogenic and antioxidant activities. Using its structure as a chemical scaffold, we synthesized and evaluated new derivatives (1\u20135), including tenuazonic-donepezil (TA-DNP) hybrids (4 and 5) due to the clinical importance of the anti-AD drug donepezil. These novel compounds all achieved activity in the micromolar range towards all selected targets and demonstrated to be potentially orally absorbed. Moreover, a selected compound (1) was further investigated as a chelating agent towards copper (II), zinc (II) and iron (III) and showed good chelating ability (pFe = 16.6, pCu = 11.6, pZn = 6.0 at pH 7.4). Therefore, the TA motif can be considered an interesting building block in the search for innovative multi-functional anti-neurodegenerative drugs, as exemplified by hybrid 5, a promising non-cytotoxic lead compound adequate for the early stages of AD, and capable of ameliorating the oxidative status of SH-SY5Y human neuroblastoma cells.<\/jats:p>","DOI":"10.3390\/biom11010111","type":"journal-article","created":{"date-parts":[[2021,1,15]],"date-time":"2021-01-15T12:44:05Z","timestamp":1610714645000},"page":"111","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Derivatives of Tenuazonic Acid as Potential New Multi-Target Anti-Alzheimer\u2019s Disease Agents"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6010-2098","authenticated-orcid":false,"given":"Viviana","family":"Poliseno","sequence":"first","affiliation":[{"name":"Department of Pharmacy and Pharmaceutical Sciences, University of Bari \u201cA. Moro\u201d, via E. Orabona 4, 70125 Bari, 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"}]},{"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\/0000-0002-7787-6639","authenticated-orcid":false,"given":"Leonardo","family":"Brunetti","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Pharmaceutical Sciences, University of Bari \u201cA. Moro\u201d, via E. Orabona 4, 70125 Bari, Italy"}]},{"given":"Fulvio","family":"Loiodice","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Pharmaceutical Sciences, University of Bari \u201cA. Moro\u201d, via E. Orabona 4, 70125 Bari, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7725-6667","authenticated-orcid":false,"given":"Antonio","family":"Carrieri","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Pharmaceutical Sciences, University of Bari \u201cA. Moro\u201d, via E. Orabona 4, 70125 Bari, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6221-6155","authenticated-orcid":false,"given":"Antonio","family":"Laghezza","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Pharmaceutical Sciences, University of Bari \u201cA. Moro\u201d, via E. Orabona 4, 70125 Bari, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1358-7376","authenticated-orcid":false,"given":"Paolo","family":"Tortorella","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Pharmaceutical Sciences, University of Bari \u201cA. Moro\u201d, via E. Orabona 4, 70125 Bari, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4890-4167","authenticated-orcid":false,"given":"Jo\u00e3o D.","family":"Magalh\u00e3es","sequence":"additional","affiliation":[{"name":"CNC\u2014Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal"}]},{"given":"Sandra M.","family":"Cardoso","sequence":"additional","affiliation":[{"name":"CNC\u2014Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"Institute of Molecular and Cell Biology, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"}]},{"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\/0000-0002-7980-5818","authenticated-orcid":false,"given":"Luca","family":"Piemontese","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Pharmaceutical Sciences, University of Bari \u201cA. Moro\u201d, via E. Orabona 4, 70125 Bari, Italy"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"(2019). 2019 Alzheimer\u2019s disease facts and figures. Alzheimer\u2019s Dement., 15, 321\u2013387.","DOI":"10.1016\/j.jalz.2019.01.010"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"33","DOI":"10.2174\/9789811401893119080004","article-title":"The Therapy of Alzheimer\u2019s Disease: Towards a New Generation of Drugs","volume":"8","author":"Piemontese","year":"2019","journal-title":"Front. Clin. Drug Res. 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