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Due to its complex pathogenesis, multi\u2010target drug design (MTDLs) strategies are considered among the most promising therapeutic approaches. In this study, we designed and synthesized a series of novel indanone derivatives targeting targets related to vascular health and dementia. The results indicated that compound C<jats:sub>5<\/jats:sub> exhibited excellent acetylcholinesterase inhibitory activity (IC<jats:sub>50<\/jats:sub> =1.16 0.41\u2005\u03bcM) and anti\u2010platelet aggregation activity (IC<jats:sub>50<\/jats:sub> =4.92\u00b10.10\u2005\u03bcM) within ranges of 0.1\u20131000\u2005\u03bcM and 0.03\u2013300\u2005\u03bcM, respectively, possibly mediated by molecular docking interactions. Furthermore, compound C<jats:sub>5<\/jats:sub> demonstrated protective effects on cells at concentrations \u226450\u2005\u03bcM, significantly reducing the release of nitric oxide (NO), tumor necrosis factor\u2010alpha (TNF\u2010\u03b1), and interleukin\u20101 beta (IL\u20101\u03b2) in a concentration\u2010dependent manner, showcasing its potent neuroinflammatory inhibitory effects. Anti\u2010inflammatory therapies are regarded as effective strategies for treating VaD. Therefore, compound C<jats:sub>5<\/jats:sub> holds promise as a novel candidate drug for further investigation into the treatment of vascular dementia.<\/jats:p>","DOI":"10.1002\/cbdv.202401931","type":"journal-article","created":{"date-parts":[[2024,11,1]],"date-time":"2024-11-01T04:39:16Z","timestamp":1730435956000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Design, Synthesis, and Anti\u2010Inflammatory Activity Evaluation of Novel Indanone Derivatives for the Treatment of Vascular Dementia"],"prefix":"10.1002","volume":"22","author":[{"given":"Xue\u2010Song","family":"Tang","sequence":"first","affiliation":[{"name":"Engineering Research Center of Bio-Process of Ministry of Education School of Food and Biological Engineering Hefei University of Technology  420 Feicui Road Hefei 230001 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin\u2010Yu","family":"He","sequence":"additional","affiliation":[{"name":"Engineering Research Center of Bio-Process of Ministry of Education School of Food and Biological Engineering Hefei University of Technology  420 Feicui Road Hefei 230001 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng\u2010Nan","family":"Li","sequence":"additional","affiliation":[{"name":"Engineering Research Center of Bio-Process of Ministry of Education School of Food and Biological Engineering Hefei University of Technology  420 Feicui Road Hefei 230001 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5433-5146","authenticated-orcid":false,"given":"Wen\u2010Cheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Engineering Research Center of Bio-Process of Ministry of Education School of Food and Biological Engineering Hefei University of Technology  420 Feicui Road Hefei 230001 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ze\u2010Yu","family":"Wu","sequence":"additional","affiliation":[{"name":"Engineering Research Center of Bio-Process of Ministry of Education School of Food and Biological Engineering Hefei University of Technology  420 Feicui Road Hefei 230001 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ai\u2010Ling","family":"Hui","sequence":"additional","affiliation":[{"name":"Engineering Research Center of Bio-Process of Ministry of Education School of Food and Biological Engineering Hefei University of Technology  420 Feicui Road Hefei 230001 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,11,26]]},"reference":[{"key":"e_1_2_9_1_1","first-page":"774","volume":"71","author":"Lesbre J. 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