{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T03:22:56Z","timestamp":1784863376408,"version":"3.55.0"},"reference-count":66,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2020,7,23]],"date-time":"2020-07-23T00:00:00Z","timestamp":1595462400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Science and Education for Smart Growth Operational Program","award":["BG05M2OP001-1.001-0003"],"award-info":[{"award-number":["BG05M2OP001-1.001-0003"]}]},{"DOI":"10.13039\/501100003336","name":"Bulgarian National Science Fund","doi-asserted-by":"publisher","award":["DN03\/9\/2016"],"award-info":[{"award-number":["DN03\/9\/2016"]}],"id":[{"id":"10.13039\/501100003336","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Galantamine (GAL) and curcumin (CU) are alkaloids used to improve symptomatically neurodegenerative conditions like Alzheimer\u2019s disease (AD). GAL acts mainly as an inhibitor of the enzyme acetylcholinesterase (AChE). CU binds to amyloid-beta (A\u03b2) oligomers and inhibits the formation of A\u03b2 plaques. Here, we combine GAL core with CU fragments and design a combinatorial library of GAL-CU hybrids as dual-site binding AChE inhibitors. The designed hybrids are screened for optimal ADME properties and BBB permeability and docked on AChE. The 14 best performing compounds are synthesized and tested in vitro for neurotoxicity and anti-AChE activity. Five of them are less toxic than GAL and CU and show activities between 41 and 186 times higher than GAL.<\/jats:p>","DOI":"10.3390\/molecules25153341","type":"journal-article","created":{"date-parts":[[2020,7,23]],"date-time":"2020-07-23T11:26:01Z","timestamp":1595503561000},"page":"3341","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Galantamine-Curcumin Hybrids as Dual-Site Binding Acetylcholinesterase Inhibitors"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8893-0346","authenticated-orcid":false,"given":"Georgi","family":"Stavrakov","sequence":"first","affiliation":[{"name":"Faculty of Pharmacy, Medical University of Sofia, 1000 Sofia, Bulgaria"},{"name":"Institute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irena","family":"Philipova","sequence":"additional","affiliation":[{"name":"Institute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atanas","family":"Lukarski","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Medical University of Sofia, 1000 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9761-0355","authenticated-orcid":false,"given":"Mariyana","family":"Atanasova","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Medical University of Sofia, 1000 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitrina","family":"Zheleva","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Medical University of Sofia, 1000 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zvetanka D.","family":"Zhivkova","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Medical University of Sofia, 1000 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Ivanov","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Medical University of Sofia, 1000 Sofia, Bulgaria"},{"name":"Institute for Bioscience and Biotechnology Research, University of Maryland, Rockville, MD 20850, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teodora","family":"Atanasova","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Medical University of Sofia, 1000 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Spiro","family":"Konstantinov","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Medical University of Sofia, 1000 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1469-1768","authenticated-orcid":false,"given":"Irini","family":"Doytchinova","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Medical University of Sofia, 1000 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,7,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1294","DOI":"10.2174\/1871527313666140917121132","article-title":"Cholinergic system dysfunction and neurodegenerative diseases: Cause or effect?","volume":"13","author":"Tata","year":"2014","journal-title":"CNS Neurol. 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