{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T11:08:04Z","timestamp":1774350484066,"version":"3.50.1"},"reference-count":96,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2024,11,18]],"date-time":"2024-11-18T00:00:00Z","timestamp":1731888000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2024,11,18]],"date-time":"2024-11-18T00:00:00Z","timestamp":1731888000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Alzheimer's disease (AD) affects millions of people and has limited treatment options, thus making it a global health concern. Amyloid \u03b2 (A\u03b2), a disrupted cholinergic system with high acetylcholinesterase (AChE), oxidative stress (OS), reduced antioxidants, and neuroinflammation are key factors influencing AD progression. Prior research has shown that AChE can interact with A\u03b2 and increase its accumulation and neurotoxicity, so targeting AChEs and A\u03b2 could be a potential therapeutic approach for AD treatment. It has been known that nonsteroidal anti\u2010inflammatory drugs (NSAIDs) can inhibit A\u03b2 accumulation. Previously, TKM01, a derivative of 4\u2010anilinoquinazoline, has demonstrated inhibitory effects against GSK\u20103\u03b2\u2014a regulator in AD progression. The current research included molecular docking studies of NSAIDs and TKM01 with A\u03b2 and AChEs as targets. TKM01 exhibited a higher binding affinity with A\u03b2 among all tested compounds. Molecular dynamic (MD) simulations confirmed the stability of the protein\u2010TKM01 complexes. TKM01 also exhibited favorable drug\u2010likeness properties, and no hepatoxicity was visualized in comparison with other compounds. Further, in vitro assay showed an inhibitory action of TKM01 (50\u20131200\u2009\u00b5g\/mL) on AChEs. In the in vivo studies on zebrafish larvae brains, we found that TKM01 (120 and 240\u2009\u00b5g\/mL) reduced the levels of AChEs and lipid peroxidation (LPO) and increased antioxidant superoxide dismutase (SOD) and catalase (CAT) in AlCl\n                    <jats:sub>3<\/jats:sub>\n                    (80\u2009\u00b5M)\u2010induced AD\u2010like model. Additionally, TKM01 treatment was found to decrease pro\u2010inflammatory cytokines TNF\u2010\u03b1, IL\u20101\u03b2, and IL\u20106. The current study demonstrates that TKM01 can be used to treat AD. Nonetheless, experimental validation is needed to reveal the cellular, sub\u2010cellular, and molecular mechanisms and possible implications at a clinical stage.\n                  <\/jats:p>","DOI":"10.1002\/jbt.70048","type":"journal-article","created":{"date-parts":[[2024,11,18]],"date-time":"2024-11-18T04:42:22Z","timestamp":1731904942000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Plausible Action of\n                    <i>N<\/i>\n                    \u2010(3,4\u2010Dimethoxy\u2010Phenyl)\u20106,7\u2010Dimethoxyquinazoline\u20104\u2010Amine (TKM01) as an Armor Against Alzheimer's Disease: In Silico and In Vivo Insights"],"prefix":"10.1002","volume":"38","author":[{"given":"Mohd","family":"Kashif","sequence":"first","affiliation":[{"name":"School of Life Sciences, B.S. 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