{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T18:37:18Z","timestamp":1791916638260,"version":"4.3.4"},"reference-count":203,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,1,15]],"date-time":"2023-01-15T00:00:00Z","timestamp":1673740800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Ministry of Education and Science of the Russian Federation","award":["075-15-2022-264"],"award-info":[{"award-number":["075-15-2022-264"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) is a neurodegenerative disorder which is characterized by \u03b2-amyloid (A\u03b2) aggregation, \u03c4-hyperphosphorylation, and loss of cholinergic neurons. The other important hallmarks of AD are oxidative stress, metal dyshomeostasis, inflammation, and cell cycle dysregulation. Multiple therapeutic targets may be proposed for the development of anti-AD drugs, and the \u201cone drug\u2013multiple targets\u201d strategy is of current interest. Tacrine (THA) was the first clinically approved cholinesterase (ChE) inhibitor, which was withdrawn due to high hepatotoxicity. However, its high potency in ChE inhibition, low molecular weight, and simple structure make THA a promising scaffold for developing multi-target agents. In this review, we summarized THA-based hybrids published from 2006 to 2022, thus providing an overview of strategies that have been used in drug design and approaches that have resulted in significant cognitive improvements and reduced hepatotoxicity.<\/jats:p>","DOI":"10.3390\/ijms24021717","type":"journal-article","created":{"date-parts":[[2023,1,16]],"date-time":"2023-01-16T02:29:55Z","timestamp":1673836195000},"page":"1717","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Tacrine-Based Hybrids: Past, Present, and Future"],"prefix":"10.3390","volume":"24","author":[{"given":"Anna","family":"Bubley","sequence":"first","affiliation":[{"name":"Chemistry Department, Lomonosov Moscow State University, Leninskie Gory 1-3, Moscow 119991, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexaner","family":"Erofeev","sequence":"additional","affiliation":[{"name":"Department of Materials Science of Semiconductors and Dielectrics, National University of Science and Technology (MISIS), Leninskiy Prospect 4, Moscow 119049, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4860-9013","authenticated-orcid":false,"given":"Peter","family":"Gorelkin","sequence":"additional","affiliation":[{"name":"Department of Materials Science of Semiconductors and Dielectrics, National University of Science and Technology (MISIS), Leninskiy Prospect 4, Moscow 119049, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6796-8241","authenticated-orcid":false,"given":"Elena","family":"Beloglazkina","sequence":"additional","affiliation":[{"name":"Chemistry Department, Lomonosov Moscow State University, Leninskie Gory 1-3, Moscow 119991, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Majouga","sequence":"additional","affiliation":[{"name":"Department of Materials Science of Semiconductors and Dielectrics, National University of Science and Technology (MISIS), Leninskiy Prospect 4, Moscow 119049, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Krasnovskaya","sequence":"additional","affiliation":[{"name":"Chemistry Department, Lomonosov Moscow State University, Leninskie Gory 1-3, Moscow 119991, Russia"},{"name":"Department of Materials Science of Semiconductors and Dielectrics, National University of Science and Technology (MISIS), Leninskiy Prospect 4, Moscow 119049, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1111\/pin.12520","article-title":"Plaque formation and the intraneuronal accumulation of \u03b2-amyloid in Alzheimer\u2019s disease","volume":"67","author":"Takahashi","year":"2017","journal-title":"Pathol. 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