{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T22:43:52Z","timestamp":1792449832273,"version":"4.5.0"},"reference-count":62,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2020,9,20]],"date-time":"2020-09-20T00:00:00Z","timestamp":1600560000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008770","name":"Anadolu \u00dcniversitesi","doi-asserted-by":"publisher","award":["Anadolu University Scientific Projects Fund, Project No: 2005S046"],"award-info":[{"award-number":["Anadolu University Scientific Projects Fund, Project No: 2005S046"]}],"id":[{"id":"10.13039\/501100008770","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Dementia is a neurological condition commonly correlated with Alzheimer\u2019s disease (AD), and it is seen with many other central nervous system (CNS) disorders. The restricted number of medications is not appropriate to offer enough relief to enhance the quality of life of patients suffering from this symptom; thus, all therapeutic choices should be carefully assessed. In this study, new thiazolylhydrazone derivatives (2a\u20132l) were designed and synthesized based on the cholinergic hypothesis. Their chemical structures were confirmed by 1H NMR, 13C NMR, and HRMS spectrometric techniques. The ADME (absorption, distribution, metabolism, elimination) parameters of the synthesized compounds were predicted by using QikProp 4.8 software. It was concluded that all compounds presented satisfactory drug-like characteristics. Furthermore, their inhibitory activities against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) in vitro were also tested by modified the Ellman spectrophotometric method. According to the results, all compounds showed a weak inhibitory effect on BChE. On the other hand, most of the compounds (2a, 2b, 2d, 2e, 2g, 2i, and 2j) had a certain AChE inhibitory activity, and the IC50 values of them were calculated as 0.063 \u00b1 0.003, 0.056 \u00b1 0.002, 0.147 \u00b1 0.006, 0.040 \u00b1 0.001, 0.031 \u00b1 0.001, 0.028 \u00b1 0.001, and 0.138 \u00b1 0.005 \u00b5M, respectively. Among these derivatives, compound 2i was found to be the most active agent in the series with an IC50 value of 0.028 \u00b1 0.001 \u00b5M, which indicated an inhibition profile at a similar rate as the reference drug, donepezil. The potential binding modes of compounds 2a, 2b, 2e, 2g, and 2i with AChE were investigated and compared with each other by the molecular docking studies. The results showed that these compounds were strongly bound up with the AChE enzyme active site with the optimal conformations.<\/jats:p>","DOI":"10.3390\/molecules25184312","type":"journal-article","created":{"date-parts":[[2020,9,20]],"date-time":"2020-09-20T21:20:28Z","timestamp":1600636828000},"page":"4312","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["Design, Synthesis, and Structure\u2013Activity Relationships of Thiazole Analogs as Anticholinesterase Agents for Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0151-6266","authenticated-orcid":false,"given":"Beg\u00fcm Nurpelin","family":"Sa\u011fl\u0131k","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, 26470 Eski\u015fehir, Turkey"},{"name":"Doping and Narcotic Compounds Analysis Laboratory, Faculty of Pharmacy, Anadolu University, 26470 Eski\u015fehir, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derya","family":"Osmaniye","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, 26470 Eski\u015fehir, Turkey"},{"name":"Doping and Narcotic Compounds Analysis Laboratory, Faculty of Pharmacy, Anadolu University, 26470 Eski\u015fehir, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulviye","family":"Acar \u00c7evik","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, 26470 Eski\u015fehir, Turkey"},{"name":"Doping and Narcotic Compounds Analysis Laboratory, Faculty of Pharmacy, Anadolu University, 26470 Eski\u015fehir, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3692-163X","authenticated-orcid":false,"given":"Serkan","family":"Levent","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, 26470 Eski\u015fehir, Turkey"},{"name":"Doping and Narcotic Compounds Analysis Laboratory, Faculty of Pharmacy, Anadolu University, 26470 Eski\u015fehir, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bet\u00fcl","family":"Kaya \u00c7avu\u015fo\u011flu","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Zonguldak B\u00fclent Ecevit University, 67600 Zonguldak, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8815-153X","authenticated-orcid":false,"given":"Yusuf","family":"\u00d6zkay","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, 26470 Eski\u015fehir, Turkey"},{"name":"Doping and Narcotic Compounds Analysis Laboratory, Faculty of Pharmacy, Anadolu University, 26470 Eski\u015fehir, Turkey"}],"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, Faculty of Pharmacy, Anadolu University, 26470 Eski\u015fehir, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1016\/S1474-4422(08)70169-8","article-title":"Alzheimer\u2019s disease and vascular dementia in developing countries: Prevalence, management, and risk factors","volume":"7","author":"Kalaria","year":"2008","journal-title":"Lancet Neurol."},{"key":"ref_2","unstructured":"Rodgers, A.B. 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