{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T05:28:02Z","timestamp":1787808482006,"version":"build-2784847793"},"reference-count":45,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2020,9,21]],"date-time":"2020-09-21T00:00:00Z","timestamp":1600646400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chemistry &amp; Biodiversity"],"published-print":{"date-parts":[[2020,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Four xanthone derivatives were synthesized and evaluated as acetylcholinesterase inhibitors (AChEIs) with metal chelating ability and antioxidant ability against Alzheimer's disease (AD). Most of them exhibited potential acetylcholinesterase (AChE), butylcholinesterase (BuChE) inhibitory, antioxidant and metal chelating properties. Among them, 1\u2010hydroxy\u20103\u2010[2\u2010(pyrrolidin\u20101\u2010yl)ethoxy]\u20109<jats:italic>H<\/jats:italic>\u2010xanthen\u20109\u2010one had the highest ability to inhibit AChE and displayed high selectivity towards AChE (IC<jats:sub>50<\/jats:sub>=2.403\u00b10.002\u2005\u03bcM for AChE and IC<jats:sub>50<\/jats:sub>=31.221\u00b10.002\u2005\u03bcM for BuChE), and it was also a good antioxidant (IC<jats:sub>50<\/jats:sub>=2.662\u00b10.003\u2005\u03bcM). Enzyme kinetic studies showed that this compound was a mixed\u2010type inhibitor, which could interact simultaneously with the catalytic anionic site (CAS) and the peripheral anionic site (PAS) of AChE. Interestingly, its copper complex showed more significant inhibitory activity for AChE (IC<jats:sub>50<\/jats:sub>=0.934\u00b10.002\u2005\u03bcM) and antioxidant activity (IC<jats:sub>50<\/jats:sub>=1.064\u00b10.003\u2005\u03bcM). Molecular dockings were carried out for the four xanthone derivatives in order to further investigate the binding modes. Finally, the blood\u2010brain barrier (BBB) penetration prediction indicated that all compounds might penetrate BBB. These results suggested that 1\u2010hydroxy\u20103\u2010[2\u2010(pyrrolidin\u20101\u2010yl)ethoxy]\u20109<jats:italic>H<\/jats:italic>\u2010xanthen\u20109\u2010one was promising AChEI with metal chelating ability and antioxidant ability for the further investigation.<\/jats:p>","DOI":"10.1002\/cbdv.202000442","type":"journal-article","created":{"date-parts":[[2020,7,21]],"date-time":"2020-07-21T18:35:08Z","timestamp":1595356508000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Design, Synthesis and Biological Evaluation of Xanthone Derivatives for Possible Treatment of Alzheimer's Disease Based on Multi\u2010Target Strategy"],"prefix":"10.1002","volume":"17","author":[{"given":"Aihong","family":"Yang","sequence":"first","affiliation":[{"name":"School of Chinese Materia Medica Tianjin University of Traditional Chinese Medicine  Tianjin 301617 P. R. 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