{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T14:01:06Z","timestamp":1790776866915,"version":"4.1.0"},"reference-count":74,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,7,12]],"date-time":"2026-07-12T00:00:00Z","timestamp":1783814400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,12]],"date-time":"2026-07-12T00:00:00Z","timestamp":1783814400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Drug Development Research"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Accumulation of amyloid\u2010\u03b2 (A\u03b2) plaques is an important cause of Alzheimer's disease (AD) pathogenesis. In this study, we evaluated A\u03b2 aggregation inhibitory activity of synthesized naphthoquinone derivatives as well as improvement in cognitive functions and metabolite profiling of brain tissues using scopolamine (SCO)\u2010induced mice. Compound\n                    <jats:bold>888<\/jats:bold>\n                    (2\u2010(4\u2010(2,3,4\u2010trimethoxybenzyl)piperazin\u20101\u2010yl)naphthalene\u20101,4\u2010dione, [TPN]) showed the highest A\u03b2 aggregation inhibitory activity (IC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u20090.14\u2009\u03bcM), and was more potent than the reference compound curcumin (IC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u20091.63\u2009\u03bcM). Compound TPN showed effective monoamine oxidase (MAO)\u2010A, MAO\u2010B, acetylcholinesterase, and butyrylcholinesterase inhibitions at 10\u2009\u03bcM, likely as candidates for multitarget\u2010directed ligands. TPN was permeable through the blood\u2010brain barrier, and non\u2010toxic to MDCK and SH\u2010SY5Y cells. TPN displayed prolonged and stable interactions with A\u03b2\n                    <jats:sub>42<\/jats:sub>\n                    during molecular dynamics simulations, in contrast to the short\u2010lived contacts observed for curcumin. Cognitive impairment was significantly improved by TPN\u2010treatment in behavioral tests. TPN treatment attenuated A\u03b2\u2010related protein expression, inflammatory responses, oxidative stress\u2010related changes, and apoptosis\u2010related alterations, while preserving hippocampal pyramidal neurons and their typical morphology. In metabolite profiling, TPN modulated a narrower set of pathways mainly related to amino acid and kynurenine metabolism, whereas donepezil induced broader adjustments involving amino acid, mitochondrial\/energy, and lipid\u2010related pathways compared to those in the serum and cortex of the SCO group, in contrast to those in the hippocampus. Collectively, a potent A\u03b2 aggregation inhibitor TPN showed significant cognitive improvement, accompanying by neuroprotective effects, decreasing inflammation, and retaining neuron structures, exhibiting changed metabolic profiles compared to the control treatments. These findings suggest that TPN has cognitive\u2010protective and neuroprotective potential under scopolamine\u2010induced impairment conditions and warrants further validation in AD\u2010relevant models.\n                  <\/jats:p>","DOI":"10.1002\/ddr.70345","type":"journal-article","created":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T05:50:00Z","timestamp":1783921800000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Ameliorative Effects of a Naphthoquinone Derivative With \u03b2\u2010Amyloid Aggregation Inhibitory Activity on Cognitive Impairment and Metabolite Analysis of the Blood and Brains of Mice"],"prefix":"10.1002","volume":"87","author":[{"given":"Jong Min","family":"Oh","sequence":"first","affiliation":[{"name":"Department of Pharmacy, College of Pharmacy Sunchon National University Suncheon Republic of Korea"},{"name":"Herbal Medicine Resources Research Center Korea Institute of Oriental Medicine Naju Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Won Kyeong","family":"Jeong","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, College of Pharmacy Sunchon National University Suncheon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun Ju","family":"Son","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, College of Pharmacy Sunchon National University Suncheon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seo Young","family":"Kim","sequence":"additional","affiliation":[{"name":"Korean Medicine (KM) Application Center, Korea Institute of Oriental Medicine (KIOM) Daegu Republic of Korea"},{"name":"University of Science and Technology (UST), Korean Convergence Medicine Major KIOM Daejeon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7184-6503","authenticated-orcid":false,"given":"Tae Woo","family":"Oh","sequence":"additional","affiliation":[{"name":"Korean Medicine (KM) Application Center, Korea Institute of Oriental Medicine (KIOM) Daegu Republic of Korea"},{"name":"University of Science and Technology (UST), Korean Convergence Medicine Major KIOM Daejeon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moongi","family":"Ji","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, College of Pharmacy Sunchon National University Suncheon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji Woo","family":"Nam","sequence":"additional","affiliation":[{"name":"Department of Chemical &amp; Biological Engineering Hanbat National University Daejeon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minyeong","family":"Baek","sequence":"additional","affiliation":[{"name":"Department of Biomedical Informatics, College of Medicine Korea University Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeong\u2010Ho","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Chemical &amp; Biological Engineering Hanbat National University Daejeon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3462-0243","authenticated-orcid":false,"given":"Woong\u2010Hee","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Biomedical Informatics, College of Medicine Korea University Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hee Jung","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, College of Pharmacy Sunchon National University Suncheon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byeongchan","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, College of Pharmacy Sunchon National University Suncheon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Man\u2010Jeong","family":"Paik","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, College of Pharmacy Sunchon National University Suncheon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hoon","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, College of Pharmacy Sunchon National University Suncheon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,12]]},"reference":[{"key":"e_1_2_9_2_1","unstructured":"Landrum.2026. 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