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Both theoretical calculations and experimental results suggested that <jats:bold>1\u20136<\/jats:bold> might serve as promising selective butyrylcholinesterase (BuChE) inhibitors and amyloid\u2010\u03b2 (A\u03b2) aggregation inhibitors. Meanwhile, experimental results confirmed the high selectivity of the derivatives, in which <jats:bold>1<\/jats:bold> had the best inhibitory activity and selectivity on BuChE (IC<jats:sub>50<\/jats:sub>\u2009=\u20090.016\u2009\u00b5M, SI\u2009=\u2009700.63). The experimental results also showed that <jats:bold>1\u20136<\/jats:bold> could act as copper chelators and reactive oxygen species (ROS) scavengers. Furthermore, in vivo experiments with <jats:italic>Caenorhabditis elegans<\/jats:italic> also showed that <jats:bold>1<\/jats:bold> could scavenge ROS and inhibit A\u03b2 aggregation. Notably, single crystals of <jats:bold>1<\/jats:bold>, <jats:bold>4<\/jats:bold>, and the <jats:bold>4<\/jats:bold>\u2010Cu(II) complex were prepared for the first time, which provided a reliable structural basis for analyzing the structure\u2013activity relationship. The dimethylamino derivatives (<jats:bold>1<\/jats:bold>, <jats:bold>4<\/jats:bold>) of \u03b1\u2010M showed the best activities and were expected to become promising candidate drugs for multifunctional anti\u2010AD.<\/jats:p>","DOI":"10.1002\/ardp.202400671","type":"journal-article","created":{"date-parts":[[2025,3,10]],"date-time":"2025-03-10T16:52:48Z","timestamp":1741625568000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Design, synthesis, biological evaluation, and X\u2010ray single crystal structure of novel computer\u2010aided\u2010drug\u2010designbased \u03b1\u2010mangostin derivatives: Multifunctional ligands against Alzheimer's disease"],"prefix":"10.1002","volume":"358","author":[{"given":"Quanzhen","family":"Chen","sequence":"first","affiliation":[{"name":"School of Chinese Materia Medica Tianjin University of Traditional Chinese Medicine Tianjin 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