{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T21:59:41Z","timestamp":1777413581281,"version":"3.51.4"},"reference-count":0,"publisher":"Bentham Science Publishers Ltd.","issue":"35","funder":[{"DOI":"10.13039\/501100000921","name":"COST Action, NECTAR, supported by COST","doi-asserted-by":"publisher","award":["CA18202"],"award-info":[{"award-number":["CA18202"]}],"id":[{"id":"10.13039\/501100000921","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003549","name":"Hungarian Scientific Research Fund","doi-asserted-by":"publisher","award":["K115480"],"award-info":[{"award-number":["K115480"]}],"id":[{"id":"10.13039\/501100003549","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e 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"}]}],"content-domain":{"domain":["eurekaselect.com"],"crossmark-restriction":true},"short-container-title":["CMC"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:sec>\n<jats:title\/>\n<jats:p>Alzheimer\u00b4s disease (AD) is the most common and severe age-dependent neurodegenerative\ndisorder worldwide. Notwithstanding the large amount of research dedicated\nto both the elucidation of this pathology and the development of an effective drug,\nthe multifaceted nature and complexity of the disease are certainly a rationale for the\nabsence of cure so far. Currently available drugs are used, mainly to compensate the decline\nof the neurotransmitter acetylcholine by acetylcholinesterase (AChE) inhibition,\nthough they only provide temporary symptomatic benefits and cannot stop AD progression.\nAlthough the multiple factors that contribute to trigger AD onset and progression\nare not yet fully understood, several pathological features and underneath pathways have\nbeen recognized to contribute to its pathology, such as metal dyshomeostasis, protein misfolding,\noxidative stress and neurotransmitter deficiencies, some of them being interconnected.\nThus, there is widespread recent interest in the development of multitarget-directed\nligands (MTDLs) for simultaneous interaction with several pathological targets of\nAD. In this review, a selection of the most recent reports (2016-up to present) on metal\nchelators of MTDLs with multifunctionalities is presented. These compounds enable the\nhitting of several AD targets or pathways, such as modulation of specific biometal ions\n(e.g., Cu, Fe, Zn) and of protein misfolding (&amp;#946;-amyloid and tau protein), anti-oxidant activity\nand AChE inhibition. The properties found for these hybrids are discussed in comparison\nwith the original reference compounds, some MTDLs being outlined as leading\ncompounds for pursuing future studies in view of efficient potential applications in AD\ntherapy.<\/jats:p>\n<\/jats:sec>","DOI":"10.2174\/0929867328666210218183032","type":"journal-article","created":{"date-parts":[[2021,2,19]],"date-time":"2021-02-19T15:55:30Z","timestamp":1613750130000},"page":"7247-7277","update-policy":"https:\/\/doi.org\/10.2174\/bsp_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Recent Multi-target Approaches on the Development of Anti- Alzheimer's Agents Integrating Metal Chelation Activity"],"prefix":"10.2174","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4069-9368","authenticated-orcid":true,"given":"M. Am\u00e9lia","family":"Santos","sequence":"first","affiliation":[{"name":"Centro de Quimica Estrutural and Departamento de Engenharia Qu\u00edmica, Instituto Superior T\u00e9cnico, Universidade de Lisboa, Av. Rovisco Pais 1, 1049-001, Lisboa,Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8554-4992","authenticated-orcid":true,"given":"S\u00edlvia","family":"Chaves","sequence":"additional","affiliation":[{"name":"Centro de Quimica Estrutural and Departamento de Engenharia Qu\u00edmica, Instituto Superior T\u00e9cnico, Universidade de Lisboa, Av. Rovisco Pais 1, 1049-001, Lisboa,Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0846-4689","authenticated-orcid":true,"given":"Katalin","family":"V\u00e1rnagy","sequence":"additional","affiliation":[{"name":"Department of Inorganic and Analytical Chemistry, University of Debrecen, Egyetem ter 1, H-4032 Debrecen,Hungary"}]}],"member":"965","container-title":["Current Medicinal Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.eurekaselect.com\/article\/download?doi=10.2174\/0929867328666210218183032","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.eurekaselect.com\/191563\/article","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.eurekaselect.com\/article\/download?doi=10.2174\/0929867328666210218183032","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,30]],"date-time":"2022-11-30T11:32:32Z","timestamp":1669807952000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.eurekaselect.com\/191563\/article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10]]},"references-count":0,"journal-issue":{"issue":"35","published-print":{"date-parts":[[2021,10]]}},"alternative-id":["LiveAll1"],"URL":"https:\/\/doi.org\/10.2174\/0929867328666210218183032","relation":{},"ISSN":["0929-8673"],"issn-type":[{"value":"0929-8673","type":"print"}],"subject":[],"published":{"date-parts":[[2021,10]]},"assertion":[{"value":"Peer Reviewed","order":0,"name":"review_status","label":"Review Status","group":{"name":"peer_review_details","label":"Peer Review Details"}},{"value":"Single blind","order":1,"name":"review_process","label":"Review Process","group":{"name":"peer_review_details","label":"Peer Review Details"}},{"value":"Checked with iThenticate","order":0,"name":"screening_status","label":"Screening Status","group":{"name":"plagiarism_screening","label":"Plagiarism Screening"}},{"value":"2020-11-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-12-29","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-01-14","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-11-16","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}