{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T19:24:46Z","timestamp":1779305086508,"version":"3.51.4"},"reference-count":36,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,11,18]],"date-time":"2024-11-18T00:00:00Z","timestamp":1731888000000},"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":[[2025,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Alzheimer's disease (AD) is multifactorial, which makes the design of multi\u2010target\u2010directed ligands an attractive strategy for the development of anti\u2010AD drugs. In order to enhance the anti\u2010AD effects and reduce the toxicity, two usnic acid (UA) derivatives (<jats:bold>1\u20132<\/jats:bold>) were designed, synthesized and fully characterized by introducing dimethylamine Schiff base moiety into the toxic \u201ctriketone\u201d portion. Ellman's method and molecular docking were used to test the cholinesterase inhibitory activities. Antioxidant activities were studied with Fenton reaction, cyclic voltammetry and <jats:italic>C. elegans<\/jats:italic>. The results showed that compared with UA, <jats:bold>1\u20132<\/jats:bold> had stronger anti\u2010cholinesterase activities and similar antioxidant activities. Notably, solvent evaporation of <jats:bold>2<\/jats:bold> and ZnCl<jats:sub>2<\/jats:sub> formed a single crystal, which was revealed to be a Zn(II) complex with UA and tertiary amine as mixed ligands by X\u2010ray diffraction. The hydrolysis of <jats:bold>2<\/jats:bold> was thus furtherly studied by HPLC. Furthermore, the crystal structure supported the replacement of toxic \u201ctriketone\u201d moiety in the chelation process, playing a detoxifying role and at the same time regulating metal homeostasis. In silico prediction also showed low hepatotoxicity and acceptable drug\u2010likeness of <jats:bold>1\u20132<\/jats:bold>. Overall, this work provided useful insights into multi\u2010target anti\u2010AD candidates with the natural product UA as the lead compound.<\/jats:p>","DOI":"10.1002\/cbdv.202401548","type":"journal-article","created":{"date-parts":[[2024,10,30]],"date-time":"2024-10-30T08:35:54Z","timestamp":1730277354000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Usnic Acid Derivatives as Multi\u2010Target Anti\u2010Alzheimer's Disease Agents: Design, Synthesis, X\u2010Ray Single Crystal Structure of Zn(II) Complex and Biological Activities"],"prefix":"10.1002","volume":"22","author":[{"given":"Lihua","family":"Zhao","sequence":"first","affiliation":[{"name":"School of Energy and Chemical Engineering, Tianjin Renai College  Tianjin 301636 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bingbing","family":"Li","sequence":"additional","affiliation":[{"name":"School of Energy and Chemical Engineering, Tianjin Renai College  Tianjin 301636 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-8805-9974","authenticated-orcid":false,"given":"Lin","family":"Zheng","sequence":"additional","affiliation":[{"name":"College of Pharmaceutical Engineering of Traditional Chinese Medicine Tianjin University of Traditional Chinese Medicine  Tianjin 301617 China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,11,18]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2022.114689"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.2174\/1566524022666220404112843"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbdv.202000442"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2019.126927"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1124\/molpharm.123.000726"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2020.112945"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2022.106301"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/joim.13759"},{"key":"e_1_2_9_9_1","first-page":"1479","volume":"20","author":"Sharma K.","year":"2019","journal-title":"Mol. Med. Rep."},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.4103\/1673-5374.245463"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.2174\/1570159X13666150716165726"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2017.04.005"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40035-020-00189-z"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2017.10.014"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2018.10.001"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12640-023-00634-7"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.accounts.9b00248"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuro.2019.07.007"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsomega.0c02306"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1166\/jbn.2021.3139"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10600-015-1376-7"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2019.111961"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2022.105539"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1080\/13543776.2018.1472239"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1070\/RC2012v081n08ABEH004245"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.saa.2021.120587"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1021\/jf204970r"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-161088"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2020.04.008"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molstruc.2022.134862"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1039\/D2TB02362H"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejps.2021.105976"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1021\/jf072383r"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molstruc.2021.130459"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2022.122458"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1063\/5.0018516"}],"container-title":["Chemistry &amp; Biodiversity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cbdv.202401548","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,23]],"date-time":"2025-03-23T06:41:12Z","timestamp":1742712072000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cbdv.202401548"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,18]]},"references-count":36,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,3]]}},"alternative-id":["10.1002\/cbdv.202401548"],"URL":"https:\/\/doi.org\/10.1002\/cbdv.202401548","archive":["Portico"],"relation":{},"ISSN":["1612-1872","1612-1880"],"issn-type":[{"value":"1612-1872","type":"print"},{"value":"1612-1880","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,18]]},"assertion":[{"value":"2024-06-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-29","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e202401548"}}