{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T20:44:54Z","timestamp":1789591494246,"version":"build-2803163510"},"reference-count":48,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,3,15]],"date-time":"2025-03-15T00:00:00Z","timestamp":1741996800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Umm Al-Qura University","award":["25UQU4290670GSSR03"],"award-info":[{"award-number":["25UQU4290670GSSR03"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: Alzheimer\u2019s disease is a complex and multifactorial brain disorder characterized by gradual memory impairment, cognitive disturbance, and severe dementia, and, ultimately, its progression leads to patient death. This research work presents the design, synthesis, and characterization of novel imidazotriazole-based thiazolidinone derivatives (1\u201314), displaying promising anti-Alzheimer\u2019s activity. Methods: These derivatives were synthesized by using 1H-imidazole-2-thiol as a starting reagent. Structural characterization was accomplished by 13C-NMR and 1H-NMR, while the molecular weight was confirmed by HREI-MS. These compounds were investigated for their anti-Alzheimer\u2019s potential under an in vitro analysis. Results: These compounds showed a significant to moderate biological potential against AChE and BChE in comparison to donepezil (IC50 = 8.50 \u00b5M and 8.90 \u00b5M against AChE and BuChE), used as a reference drug. Among these compounds, analog 10 with IC50 values of 6.70 \u00b5M and 7.10 \u00b5M against AChE and BuChE emerged as the lead compound of the series with promising biological efficacy against targeted enzymes. Molecular docking revealed the interactive nature of active ligands against target enzymes. These compounds were also assessed under dynamic conditions to examine the structural deviation and conformational changes in a protein complex structure. DFT calculations provided the relative stability and reactivity of the lead compounds. An ADMET analysis showed that these compounds have no toxicological profile. Conclusions: This research study paves the way for the further development and optimization of novel and selective imidazotriazole-based thiazolidinone inhibitors as potent anti-Alzheimer\u2019s agents.<\/jats:p>","DOI":"10.3390\/ph18030415","type":"journal-article","created":{"date-parts":[[2025,3,17]],"date-time":"2025-03-17T07:49:57Z","timestamp":1742197797000},"page":"415","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Synthesis, Molecular Simulation, DFT, and Kinetic Study of Imidazotriazole-Based Thiazolidinone as Dual Inhibitor of Acetylcholinesterase and Butyrylcholinesterase Enzymes"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5294-2193","authenticated-orcid":false,"given":"Manal M.","family":"Khowdiary","sequence":"first","affiliation":[{"name":"Department of Chemistry, Faculty of Applied Science, University College-Al Leith, University of Umm Al-Qura, Makkah 21955, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5404-0954","authenticated-orcid":false,"given":"Shoaib","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Abbottabad University of Science and Technology, Abbottabad 22500, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tayyiaba","family":"Iqbal","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Abbottabad University of Science and Technology, Abbottabad 22500, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wajid","family":"Rehman","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Hazara Univeristy, Mansehra 21120, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad Bilal","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Abbottabad University of Science and Technology, Abbottabad 22500, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mujaddad Ur","family":"Rehman","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Abbottabad University of Science and Technology, Abbottabad 22500, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zanib","family":"Fiaz","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Abbottabad University of Science and Technology, Abbottabad 22500, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Hakimullah","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Balochistan University of Information and Technology, Engineering & Management Sciences, Quetta 87300, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"445","DOI":"10.31887\/DCNS.2013.15.4\/hjahn","article-title":"Memory loss in Alzheimer\u2019s disease","volume":"31","author":"Jahn","year":"2013","journal-title":"Dialogues Clin. 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