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Given that A\u03b2 aggregation and plaque formation are a central pathological feature of Alzheimer\u2019s disease (AD), BACE1 remains a critical therapeutic target. Furthermore, the complexity of AD pathology necessitates the identification of novel multi-target agents. This study employed a structure-based virtual screening, targeting the BACE1 approach to identify the potential BACE1 inhibitors from FDA-approved drug scaffolds derived from the ZINC database. Top-ranked candidates were subsequently validated through extensive 500 ns molecular dynamics (MD) simulations and\n                    <jats:italic>in vitro<\/jats:italic>\n                    assays of BACE1 inhibition activity. Furthermore, multi-AD-related target profiling of candidates was conducted using molecular docking and a series of\n                    <jats:italic>in vitro<\/jats:italic>\n                    assays. Among them, ZINC000019796155 emerged as a promising multi-target compound. Biochemical analysis revealed that ZINC000019796155 exhibited moderate inhibitory effects against BACE1. Subsequent assays confirmed its capacity to inhibit butyrylcholinesterase (BuChE) action and A\u03b2 aggregation, function as a free radical scavenger, and provide neuroprotection against H\u2082O\u2082-induced oxidative stress in cellular models. Furthermore,\u00a0western blot analysis elucidated the mechanism of neuroprotection, indicating that ZINC000019796155 inhibits the apoptotic pathway while simultaneously suppressing the formation of A\u03b2 plaques and neurofibrillary tangles (NFTs). These findings highlight ZINC000019796155 as a validated scaffold with a known safety profile for AD. While further structural optimization and preclinical in vivo studies are necessary, this study underscores the potential of ZINC000019796155 as a multi-target neuroprotective agent for AD treatment.\n                  <\/jats:p>","DOI":"10.1038\/s41598-026-46708-2","type":"journal-article","created":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T07:07:12Z","timestamp":1775545632000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Repurposing FDA-approved drugs as multi-target neuroprotective agents for Alzheimer\u2019s disease via computational screening and experimental validation"],"prefix":"10.1038","volume":"16","author":[{"given":"Khemjira","family":"Phemphunananchai","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pornthip","family":"Waiwut","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jutarop","family":"Phetcharaburanin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pattaporn","family":"Poonsawas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chantana","family":"Boonyarat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,7]]},"reference":[{"key":"46708_CR1","doi-asserted-by":"crossref","unstructured":"Alzheimer\u2019s Association. 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