{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T03:09:35Z","timestamp":1791256175437,"version":"4.1.0"},"reference-count":37,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T00:00:00Z","timestamp":1772668800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Zayed Bin Sultan Center for Health Sciences","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"name":"UAEU-University of Sharjah","award":["#12R282"],"award-info":[{"award-number":["#12R282"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    Alzheimer\u2019s is the leading factor behind dementia, producing steady impairments in memory, cognitive reasoning, behavioral, and social interactions. This scientific study investigates thirty-two phenoxy tacrine (PhO-THA) derivatives through an integrated computational modeling to identify potential therapeutic candidates. 3D-QSAR models were developed using comparative molecular similarity indices analysis and comparative molecular field analysis, which were subjected to rigorous internal and external validation to establish a robust quantitative relationship between molecular interaction fields and cytotoxic activities. Based on these validated structural insights, fourteen new compounds (D1-D14) were designed. Comprehensive molecular docking and molecular dynamics (MD) simulations, coupled with ADME-Tox profiling, were used to evaluate their pharmacological potential. Our results highlight four specific compounds (D9-D12) that exhibit favorable pharmacokinetic properties and a high safety profile, making them promising candidates for future drug development. D9 was selected for MD simulations due to its lower cytotoxic activity (pIC\n                    <jats:sub>50<\/jats:sub>\n                    of 3.50), which is comparable to the reference THA drug (pIC\n                    <jats:sub>50<\/jats:sub>\n                    of 3.52). The results demonstrated exceptional thermodynamic stability for D9 upon complexation with the NMDA receptor (PDB ID: 5EWJ) over a 100 ns simulation time.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0343723","type":"journal-article","created":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T18:39:52Z","timestamp":1772735992000},"page":"e0343723","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":5,"title":["Computational modeling for rational design of novel phenoxy tacrine derivatives targeting Alzheimer\u2019s disease"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2211-3298","authenticated-orcid":true,"given":"Mohamed","family":"El Fadili","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed","family":"Er-rajy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Somdutt","family":"Mujwar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1766-4471","authenticated-orcid":true,"given":"Abdelouahid","family":"Samadi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2344-5101","authenticated-orcid":true,"given":"Samir","family":"Chtita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Menana","family":"Elhallaoui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,3,5]]},"reference":[{"issue":"1","key":"pone.0343723.ref001","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1186\/s13024-020-00391-7","article-title":"Molecular 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