{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T09:09:01Z","timestamp":1788858541748,"version":"build-2803163510"},"reference-count":44,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T00:00:00Z","timestamp":1787616000000},"content-version":"vor","delay-in-days":24,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004242","name":"Princess Nourah Bint Abdulrahman University","doi-asserted-by":"publisher","award":["PNURSP2026R342"],"award-info":[{"award-number":["PNURSP2026R342"]}],"id":[{"id":"10.13039\/501100004242","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chemistry &amp;amp; Biodiversity"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    In this study,\n                    <jats:italic>bis<\/jats:italic>\n                    \u2010Schiff base derivatives bearing 4\u2010hydroxyacetophenone were synthesized and assessed for their in vitro acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory activities. In the series, compound (\n                    <jats:bold>2i<\/jats:bold>\n                    ) was identified as the most promising inhibitor of AChE (IC\n                    <jats:sub>50<\/jats:sub>\n                    \u00a0=\u00a014.82\u00a0\u00b1\u00a00.09\u00a0\u00b5M) and BuChE (IC\n                    <jats:sub>50<\/jats:sub>\n                    \u00a0=\u00a027.91\u00a0\u00b1\u00a00.16\u00a0\u00b5M) enzymes surpassing the standard drug galantamine, while the remaining derivatives showed good to moderate inhibition. Structure\u2013activity relationship (SAR) study exposed those methoxy groups attached to the benzene ring significantly improved enzyme inhibition, while electron\u2010withdrawing groups led to condensed the activities. Molecular docking simulations against AChE and BuChE revealed distinct binding modes, with\n                    <jats:bold>2i<\/jats:bold>\n                    forming critical bonds with catalytic residues. Quantum chemical analysis established strong correlations between electrophilicity index (\n                    <jats:italic>\u03c9<\/jats:italic>\n                    \u00a0=\u00a04.712\u00a0eV for\n                    <jats:bold>2i<\/jats:bold>\n                    ), HOMO\u2013LUMO gap (4.287\u00a0eV), and experimental inhibition. Quantum Theory of Atoms in Molecules (QTAIM) analysis supporting\u00a0optimal electron density distribution and favorable non\u2010covalent interaction patterns. Comprehensive in silico ADMET profiling predicted excellent pharmacokinetic properties for all derivatives, with 96%\u2013100% human oral absorption, moderate blood\u2013brain barrier (BBB) penetration for\n                    <jats:bold>2i<\/jats:bold>\n                    , and low cardiac toxicity risk. The integrated computational\u2010experimental approach provides supportive evidence for rational design of next\u2010generation cholinesterase inhibitors with optimized efficacy and safety profiles.\n                  <\/jats:p>","DOI":"10.1002\/cbdv.71630","type":"journal-article","created":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T18:01:00Z","timestamp":1787680860000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Synthesis of 4\u2010Hydroxyacetophenone\u2010Derived\n                    <i>Bis<\/i>\n                    \u2010Schiff Bases as Potent Cholinesterase Inhibitors: In Vitro Evaluation, Molecular Docking, DFT, and ADMET Analysis"],"prefix":"10.1002","volume":"23","author":[{"given":"Muhammad","family":"Daud","sequence":"first","affiliation":[{"name":"Department of Chemistry University of Malakand  Dir Lower 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Ali","family":"Shah","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy Universiti Teknologi MARA Cawangan Selangor Kampus Puncak Alam Bandar Puncak Alam Selangor Malaysia"},{"name":"Atta\u2010ur\u2010Rahman Institute for Natural Product Discovery (AuRIns) Universiti Teknologi MARA Cawangan Selangor Kampus Puncak Alam  Bandar Puncak Alam Selangor Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Syahrul","family":"Imran","sequence":"additional","affiliation":[{"name":"Atta\u2010ur\u2010Rahman Institute for Natural Product Discovery (AuRIns) Universiti Teknologi MARA Cawangan Selangor Kampus Puncak Alam  Bandar Puncak Alam Selangor Malaysia"},{"name":"Faculty of Applied Sciences Universiti Teknologi MARA Shah Alam  Shah Alam Selangor Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1042-8126","authenticated-orcid":false,"given":"Ashwag 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