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Multi\u2010target\u2010directed ligands (MTDLs) offer a promising strategy by integrating multiple pharmacophores into single molecules. The aim of this study was the design, synthesis, and evaluation of the 12 novel 1,3,5\u2010triazine\u2013aniline\u2013benzylidene derivatives (\n                    <jats:bold>6a\u2013l<\/jats:bold>\n                    ) as the MTDLs targeting cholinesterases (ChEs), oxidative stress, and biometal dyshomeostasis implicated in AD. In vitro assays showed several compounds exhibited moderate dual ChEs inhibition, with notable selectivity towards butyrylcholinesterase (BChE). Compounds bearing 3,4\u2010dihydroxybenzylidene moieties (\n                    <jats:bold>6i<\/jats:bold>\n                    ,\n                    <jats:bold>6j<\/jats:bold>\n                    ) displayed potent BChE inhibition, reaching sub\u2010micromolar levels. Furthermore, many derivatives demonstrated strong antioxidant activity in the 2,2\u2010diphenyl\u20101\u2010picrylhydrazyl (DPPH) assay, with several exhibiting low micromolar EC\n                    <jats:sub>50<\/jats:sub>\n                    values (1.00\u20137.08\u00a0\u00b5M), superior to the standard antioxidants butylated hydroxytoluene (BHT) and quercetin, particularly those containing dihydroxy substitutions. The UV\u2013Vis spectroscopy method confirmed the compound's ability to chelate to the relevant biometal ions (Cu\n                    <jats:sup>2+<\/jats:sup>\n                    , Zn\n                    <jats:sup>2+<\/jats:sup>\n                    , Fe\n                    <jats:sup>2+<\/jats:sup>\n                    , Fe\n                    <jats:sup>3+<\/jats:sup>\n                    , and Al\n                    <jats:sup>3+<\/jats:sup>\n                    ), especially with Cu\n                    <jats:sup>2+<\/jats:sup>\n                    . Molecular docking studies for the representative dual ChEs inhibitor molecule (\n                    <jats:bold>6j<\/jats:bold>\n                    ) supported the biological findings, revealing effective interactions with the amino acids within the active sites of both ChEs. These results underscore the potential of these novel hybrids as promising MTDL leads for further AD therapeutic development.\n                  <\/jats:p>","DOI":"10.1002\/cbdv.202502653","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T12:44:29Z","timestamp":1772973869000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Synthesis and Biological Evaluations of the 1,3,5\u2010Triazine Derivatives as Cholinesterase Inhibitors, Antioxidant, and Biometal Chelators for Alzheimer's Disease"],"prefix":"10.1002","volume":"23","author":[{"given":"Fardin","family":"Mahdipanah","sequence":"first","affiliation":[{"name":"Department of Medicinal Chemistry School of Pharmacy Tabriz University of Medical Sciences  Tabriz Iran"},{"name":"Student Research Committee Tabriz University of Medical Sciences  Tabriz 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