{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T13:40:24Z","timestamp":1791639624454,"version":"4.3.4"},"reference-count":61,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T00:00:00Z","timestamp":1782086400000},"content-version":"vor","delay-in-days":21,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"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":["Chem Biol Drug Des"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The development of multifunctional small molecules capable of simultaneously modulating multiple pathological pathways represents a rational strategy in medicinal chemistry for complex disorders such as Alzheimer's disease (AD) and cancer. Herein, a novel series of methoxyphenol\u2010based 1,2,3\u2010triazole hybrids (\n                    <jats:bold>5a\u2013h<\/jats:bold>\n                    ) was designed and synthesized via Cu(I)\u2010catalyzed azide\u2013alkyne cycloaddition (CuAAC). All derivatives were fully characterized by FT\u2010IR,\n                    <jats:sup>1<\/jats:sup>\n                    H\/\n                    <jats:sup>13<\/jats:sup>\n                    C NMR spectroscopy, and elemental analysis. Biological evaluation encompassed in\u00a0vitro antioxidant screening (DPPH\u2022, ABTS\u2022\n                    <jats:sup>+<\/jats:sup>\n                    , and CUPRAC), acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibition (modified Ellman method), and antiproliferative activity against the PC3 prostate cancer cell line using HDF\u20101 healthy fibroblasts as a selectivity control. Compound\n                    <jats:bold>5c<\/jats:bold>\n                    proved the most potent AChE inhibitor (IC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u20091.44\u2009\u00b1\u20090.33\u2009\u03bcM; SI\u2009=\u200916.77), while\n                    <jats:bold>5h<\/jats:bold>\n                    exhibited preferential BuChE inhibition (IC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u200911.40\u2009\u00b1\u20091.25\u2009\u03bcM). Enzyme kinetic studies confirmed a mixed\u2010type inhibition mechanism for both lead compounds, suggesting dual\u2010site engagement within the cholinesterase gorge. In the antiproliferative assay,\n                    <jats:bold>5e<\/jats:bold>\n                    and\n                    <jats:bold>5c<\/jats:bold>\n                    surpassed the reference drug methotrexate (IC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u20094.42\u2009\u00b1\u20090.15\u2009\u03bcM) with IC\n                    <jats:sub>50<\/jats:sub>\n                    values of 3.57\u2009\u00b1\u20090.11\u2009\u03bcM and 3.89\u2009\u00b1\u20090.20\u2009\u03bcM, respectively, alongside favorable selectivity over healthy fibroblasts. In silico ADMET profiling confirmed drug\u2010likeness for all derivatives, and DFT calculations at the B3LYP\/6\u2010311++G(d,p) level provided electronic rationale for observed reactivity trends. Molecular docking against human AChE (PDB: 4EY7) and BuChE (PDB: 4BDS) rationalized key stabilizing interactions including \u03c0\u2013\u03c0 stacking with Trp86\/Trp286 and hydrogen bonding with active\u2010site residues. Collectively, these findings identify the methoxyphenol\u2013triazole scaffold as a promising lead platform warranting further optimization for multitarget therapeutic applications in neurodegenerative and oncological disorders.\n                  <\/jats:p>","DOI":"10.1111\/cbdd.70343","type":"journal-article","created":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T05:02:53Z","timestamp":1782190973000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Biological and In Silico Evaluation of Novel Methoxyphenol\u20131,2,3\u2010Triazole Hybrids as Multifunctional Anti\u2010Alzheimer's and Anticancer Agents"],"prefix":"10.1111","volume":"107","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4305-9638","authenticated-orcid":false,"given":"Sultan","family":"Onur","sequence":"first","affiliation":[{"name":"Department of Chemistry, Faculty of Sciences Kahramanmara\u015f S\u00fct\u00e7\u00fc \u0130mam University  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