{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T20:14:29Z","timestamp":1778012069831,"version":"3.51.4"},"reference-count":58,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2018,8,29]],"date-time":"2018-08-29T00:00:00Z","timestamp":1535500800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>A few symptomatic drugs are currently available for Alzheimer\u2019s Disease (AD) therapy, but these molecules are only able to temporary improve the cognitive capacity of the patients if administered in the first stages of the pathology. Recently, important advances have been achieved about the knowledge of this complex condition, which is now considered a multi-factorial disease. Researchers are, thus, more oriented toward the preparation of molecules being able to contemporaneously act on different pathological features. To date, the inhibition of acetylcholinesterase (AChE) and of \u03b2-amyloid (A\u03b2) aggregation as well as the antioxidant activity and the removal and\/or redistribution of metal ions at the level of the nervous system are the most common investigated targets for the treatment of AD. Since many natural compounds show multiple biological properties, a series of secondary metabolites of plants or fungi with suitable structural characteristics have been selected and assayed in order to evaluate their potential role in the preparation of multi-target agents. Out of six compounds evaluated, 1 showed the best activity as an antioxidant (EC50 = 2.6 \u00b1 0.2 \u03bcmol\/\u00b5mol of DPPH) while compound 2 proved to be effective in the inhibition of AChE (IC50 = 6.86 \u00b1 0.67 \u03bcM) and A\u03b21\u201340 aggregation (IC50 = 74 \u00b1 1 \u03bcM). Furthermore, compound 6 inhibited BChE (IC50 = 1.75 \u00b1 0.59 \u03bcM) with a good selectivity toward AChE (IC50 = 86.0 \u00b1 15.0 \u03bcM). Moreover, preliminary tests on metal chelation suggested a possible interaction between compounds 1, 3 and 4 and copper (II). Molecules with the best multi-target profiles will be used as starting hit compounds to appropriately address future studies of Structure-Activity Relationships (SARs).<\/jats:p>","DOI":"10.3390\/molecules23092182","type":"journal-article","created":{"date-parts":[[2018,8,30]],"date-time":"2018-08-30T02:49:34Z","timestamp":1535597374000},"page":"2182","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Natural Scaffolds with Multi-Target Activity for the Potential Treatment of Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7980-5818","authenticated-orcid":false,"given":"Luca","family":"Piemontese","sequence":"first","affiliation":[{"name":"Dipartimento di Farmacia-Scienze del Farmaco, Universit\u00e0 degli Studi di Bari \u201cAldo Moro\u201d, Via E. Orabona 4, 70125 Bari, Italy"},{"name":"Consiglio Nazionale delle Ricerche-Istituto di Scienze delle Produzioni Alimentari (CNR-ISPA), via Amendola, 122\/O, 70125 Bari, Italy"},{"name":"Consortium C.I.N.M.P.I.S., Via E. Orabona 4, 70125 Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9859-7508","authenticated-orcid":false,"given":"Gabriele","family":"Vitucci","sequence":"additional","affiliation":[{"name":"Consiglio Nazionale delle Ricerche-Istituto di Scienze delle Produzioni Alimentari (CNR-ISPA), via Amendola, 122\/O, 70125 Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8411-304X","authenticated-orcid":false,"given":"Marco","family":"Catto","sequence":"additional","affiliation":[{"name":"Dipartimento di Farmacia-Scienze del Farmaco, Universit\u00e0 degli Studi di Bari \u201cAldo Moro\u201d, Via E. Orabona 4, 70125 Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6221-6155","authenticated-orcid":false,"given":"Antonio","family":"Laghezza","sequence":"additional","affiliation":[{"name":"Dipartimento di Farmacia-Scienze del Farmaco, Universit\u00e0 degli Studi di Bari \u201cAldo Moro\u201d, Via E. Orabona 4, 70125 Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8735-8165","authenticated-orcid":false,"given":"Filippo Maria","family":"Perna","sequence":"additional","affiliation":[{"name":"Dipartimento di Farmacia-Scienze del Farmaco, Universit\u00e0 degli Studi di Bari \u201cAldo Moro\u201d, Via E. Orabona 4, 70125 Bari, Italy"},{"name":"Consortium C.I.N.M.P.I.S., Via E. 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