{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T04:23:24Z","timestamp":1791606204258,"version":"4.3.4"},"reference-count":66,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,1,10]],"date-time":"2025-01-10T00:00:00Z","timestamp":1736467200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,1,10]],"date-time":"2025-01-10T00:00:00Z","timestamp":1736467200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemistryOpen"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The inhibition of acetylcholinesterase (AChE), an enzyme responsible for the inactivation and decrease in acetylcholine in the cholinergic pathway, has been considered an attractive target for small\u2010molecule drug discovery in Alzheimer's disease (AD) therapy. In the present study, a series of TZD derivatives were designed, synthesized, and studied for drug likeness, blood\u2013brain barrier (BBB) permeability, and adsorption, distribution, metabolism, excretion, and toxicity (ADMET). Additionally, docking studies of the designed compounds were performed on AChE. Additionally, all the TZD derivatives (CHT1\u20105) showed an acceptable affinity for AChE inhibition, and the results showed convincing binding modes in the active site of AChE. Among them, 5\u2010(4\u2010methoxybenzylidene) thiazolidine\u20102,4\u2010dione (CHT1) was identified as the most potent AChE inhibitor (IC\n                    <jats:sub>50<\/jats:sub>\n                    of 165.93\u2005nM) with the highest antioxidant activity. Following the exposure of PC12 cells to A\u03b21\u201042 (100\u2005\u03bcM), a marked reduction in cell survival was observed. Pretreatment of PC12 cells with TZD derivatives had a neuroprotective effect and significantly enhanced cell survival in response to A\u03b2\u2010induced toxicity. Western blotting analysis revealed that CHT1 (5 and 8\u2005\u03bcM) downregulated p\u2010Tau and HSP70 expression levels. The results indicate that CHT1 is a promising and effective AchE\u2010I that could be utilized as a powerful candidate against AD.\n                  <\/jats:p>","DOI":"10.1002\/open.202400294","type":"journal-article","created":{"date-parts":[[2025,1,11]],"date-time":"2025-01-11T02:00:03Z","timestamp":1736560803000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Investigation of Thiazolidine\u20102,4\u2010Dione Derivatives as Acetylcholinesterase Inhibitors: Synthesis,\n                    <i>In Vitro<\/i>\n                    Biological Activities and\n                    <i>In Silico<\/i>\n                    Studies"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-3004-9418","authenticated-orcid":false,"given":"Hanane","family":"Naeimi","sequence":"first","affiliation":[{"name":"Department of Biology Faculty of Basic Sciences University of Guilan  Rasht 4193833697 Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-8663-6810","authenticated-orcid":false,"given":"Maryam","family":"Taheri","sequence":"additional","affiliation":[{"name":"Department of Biology Faculty of Basic Sciences University of Guilan  Rasht 4193833697 Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2245-0697","authenticated-orcid":false,"given":"Hossein","family":"Ghafouri","sequence":"additional","affiliation":[{"name":"Department of Biology Faculty of Basic Sciences University of Guilan  Rasht 4193833697 Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6667-2641","authenticated-orcid":false,"given":"Asadollah","family":"Mohammadi","sequence":"additional","affiliation":[{"name":"Department of Chemistry Faculty of Sciences University of Guilan  Rasht 4193833697 Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,1,10]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(16)00062-4"},{"key":"e_1_2_8_2_1","first-page":"85","volume":"13","author":"Kidd P. 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