{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T13:18:33Z","timestamp":1784726313583,"version":"3.55.0"},"reference-count":29,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,12,13]],"date-time":"2022-12-13T00:00:00Z","timestamp":1670889600000},"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":[[2023,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Coumarins and their derivatives possessed a variety of biological activities and some of coumarin\u2010based drugs have been approved by the US Food and Drug Administration. Alzheimer's disease (AD) has caused great losses to human society. However, due to its complex pathogenesis, the ideal therapeutic approach has not been found yet. Free radical scavenging activity which is one of the main activities of coumarin core structure is closely related to other anti\u2010AD activities. Therefore, in this work coumarins were chosen as privileged lead compounds for the development of anti\u2010AD drugs based on strategy of multi\u2010target directed ligands (MTDLs). Derivatives <jats:bold>1<\/jats:bold>\u2013<jats:bold>3<\/jats:bold> which could modulate multiple targets simultaneously, including ROS, cholinesterase, \u03b2amyloid (A\u03b2) aggregation, and metal dyshomeostasis were designed and for the first time synthesized. Their anti\u2010AD activities were studied both <jats:italic>in\u2005vitro<\/jats:italic> and <jats:italic>in\u2005silico<\/jats:italic>. Results showed that <jats:bold>1<\/jats:bold>\u2013<jats:bold>3<\/jats:bold> possessed potent antioxidant activities and 7\u2010OH group did change the electron distribution of the molecule and enhance the antioxidant activities. They also have good inhibition activities on acetylcholinesterase (AChE) and A\u03b2 aggregation and compound <jats:bold>1<\/jats:bold> had the strongest AChE inhibitory effect among the three compounds (AChE IC<jats:sub>50<\/jats:sub>=11.15\u2005\u03bcM). Compound <jats:bold>1<\/jats:bold>\u2013<jats:bold>3<\/jats:bold> could also selectively chelate with Cu<jats:sup>2+<\/jats:sup> and Al<jats:sup>3+<\/jats:sup> to regulate the metal homeostasis. <jats:italic>In\u2005silico<\/jats:italic> simulations, including molecular docking and prediction of ADMET performance, indicated that <jats:bold>1<\/jats:bold>\u2013<jats:bold>3<\/jats:bold> could interact with target proteins and cross the blood brain barrier. In conclusion, <jats:bold>1<\/jats:bold>\u2013<jats:bold>3<\/jats:bold> could be promising MTDLs applied as anti\u2010AD candidate drugs.<\/jats:p>","DOI":"10.1002\/cbdv.202200867","type":"journal-article","created":{"date-parts":[[2022,12,3]],"date-time":"2022-12-03T15:14:32Z","timestamp":1670080472000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Design, Synthesis, Calculation and Biological Activity Studies Based on Privileged Coumarin Derivatives as Multifunctional Anti\u2010AD Lead Compound"],"prefix":"10.1002","volume":"20","author":[{"given":"Huiyan","family":"Wang","sequence":"first","affiliation":[{"name":"School of Environmental and Chemical Engineering Jiangsu Ocean University  222005 Lianyungang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengyang","family":"Su","sequence":"additional","affiliation":[{"name":"School of Pharmacy Jiangsu Ocean University  222005 Lianyungang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuli","family":"Shi","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica Tianjin University of Traditional Chinese Medicine  301617 Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangyu","family":"Li","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica Tianjin University of Traditional Chinese Medicine  301617 Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyu","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Environmental and Chemical Engineering Jiangsu Ocean University  222005 Lianyungang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0827-655X","authenticated-orcid":false,"given":"Aihong","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica Tianjin University of Traditional Chinese Medicine  301617 Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Shen","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica Tianjin University of Traditional Chinese Medicine  301617 Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,12,13]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.2174\/1389557520666200429101053"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1039\/D0NJ05688J"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1039\/C8NJ00383A"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jafc.1c05792"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jcim.9b01083"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsmedchemlett.9b00069"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejps.2020.105424"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.2174\/1871526518666180628124323"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.2174\/092986711803414368"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1615\/CritRevEukaryotGeneExpr.2018022258"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1039\/D0FO01041C"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2022.101619"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1039\/D1NJ02950A"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molstruc.2022.133747"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00204-019-02538-y"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/ddr.21587"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2018.10.056"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules24234335"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbdv.202000442"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejps.2021.105976"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molstruc.2021.130459"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2021.128316"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2022.114216"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2007.09.006"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00418-016-1464-1"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm020017n"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1089\/jmf.2014.3292"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.22885"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2002-35661"}],"container-title":["Chemistry &amp; 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