{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T06:37:57Z","timestamp":1792737477647,"version":"4.5.0"},"reference-count":40,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T00:00:00Z","timestamp":1789344000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T00:00:00Z","timestamp":1789344000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004410","name":"T\u00fcrkiye Bilimsel ve Teknolojik Ara\u015ftirma Kurumu","doi-asserted-by":"publisher","award":["1649B032405044"],"award-info":[{"award-number":["1649B032405044"]}],"id":[{"id":"10.13039\/501100004410","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Drug Development Research"],"published-print":{"date-parts":[[2026,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Alzheimer's disease (AD) is a progressive neurodegenerative disease, and cholinergic dysfunction is considered one of the fundamental pathological factors of this disease. Guided by the clinically used acetylcholinesterase (AChE) inhibitor donepezil, we explored trimetazidine dihydrochloride as an accessible starting scaffold to generate donepezil\u2010like features and to develop new anti\u2010AD candidates. Accordingly, 20 novel hydrazone derivatives were designed and synthesized based on trimetazidine dihydrochloride, and their structures were confirmed by spectroscopic methods. The compounds were evaluated for in vitro inhibition of AChE and butyrylcholinesterase (BChE) using donepezil and tacrine as reference inhibitors, respectively. Several derivatives displayed pronounced AChE inhibition, whereas most compounds showed weak or negligible activity toward BChE, indicating a generally favorable AChE\u2010selective profile. Among the series, compounds\n                    <jats:bold>3p<\/jats:bold>\n                    ,\n                    <jats:bold>3q<\/jats:bold>\n                    and\n                    <jats:bold>3r<\/jats:bold>\n                    exhibited selective inhibitory activity against AChE comparable to donepezil, with IC\n                    <jats:sub>50<\/jats:sub>\n                    values of 0.030\u2009\u00b1\u20090.001\u2009\u03bcM, 0.085\u2009\u00b1\u20090.003\u2009\u03bcM and 0.034\u2009\u00b1\u20090.001\u2009\u03bcM, respectively. To rationalize the observed activity trends, molecular docking studies were performed, suggesting that the most active ligands adopt donepezil\u2010like binding modes spanning the catalytic and peripheral anionic sites and are further stabilized by \u03c0\u2013\u03c0\/\u03c0\u2013cation contacts and hydrogen\u2010bonding interactions within the active gorge. Overall, these findings identify trimetazidine\u2010derived hydrazide\u2010hydrazones as a promising chemotype for the development of selective AChE inhibitors and provide a basis for further optimization and advanced biological validation.\n                  <\/jats:p>","DOI":"10.1002\/ddr.70382","type":"journal-article","created":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T08:36:31Z","timestamp":1789374991000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Design, Synthesis and Molecular Docking Studies of Some Novel Hydrazone Derivatives Based on Trimetazidine as Selective and Potent AChE Inhibitors"],"prefix":"10.1002","volume":"87","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3911-6858","authenticated-orcid":false,"given":"Muhammed O\u011fuzhan","family":"Do\u011fan","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Chemistry Faculty of Pharmacy, Marmara University \u0130stanbul T\u00fcrkiye"},{"name":"Department of Pharmaceutical Chemistry Institute of Health Sciences, Marmara University \u0130stanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0151-6266","authenticated-orcid":false,"given":"Beg\u00fcm Nurpelin Sa\u011fl\u0131k","family":"\u00d6zkan","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry Faculty of Pharmacy, Anadolu University Eski\u015fehir T\u00fcrkiye"},{"name":"Central Research Laboratory (MERLAB) Faculty of Pharmacy, Anadolu University Eski\u015fehir T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0434-1334","authenticated-orcid":false,"given":"Abdullah Burak","family":"Karaduman","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Toxicology Faculty of Pharmacy, Anadolu University Eski\u015fehir T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7911-8372","authenticated-orcid":false,"given":"Sevgi","family":"Karaku\u015f","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry Faculty of Pharmacy, Istanbul Aydin University \u0130stanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuf","family":"\u00d6zkay","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry Faculty of Pharmacy, Anadolu University Eski\u015fehir T\u00fcrkiye"},{"name":"Central Research Laboratory (MERLAB) Faculty of Pharmacy, Anadolu University Eski\u015fehir T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2252-0923","authenticated-orcid":false,"given":"Zafer As\u0131m","family":"Kaplanc\u0131kl\u0131","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry 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