Repurposing of FDA-Approved Drugs as Acetylcholinesterase Inhibitors for Alzheimer's Disease: A Combined In Silico and In Vitro Evaluation and Structure-Activity Relationship

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dc.authorid0000-0003-2552-038X
dc.authorid0000-0002-4037-1979
dc.contributor.authorSikik, Merve
dc.contributor.authorComert Onder, Ferah
dc.date.accessioned2026-02-03T12:03:10Z
dc.date.available2026-02-03T12:03:10Z
dc.date.issued2025
dc.departmentÇanakkale Onsekiz Mart Üniversitesi
dc.description.abstractAlzheimer's disease (AD) is a progressive neurodegenerative disorder that is characterized by cognitive decline and decreased cholinergic activity that affects millions of individuals worldwide. Herein, in vitro acetylcholinesterase (AChE) inhibitory potentials of FDA-approved drugs identified by computational approaches, including structure-based virtual screening, molecular dynamics (MD) simulations, and molecular mechanics-generalized Born surface area (MM/GBSA), were carried out. The top docking poses of the selected drugs (Trazodone, Frovatriptan, Eletriptan, Bupropion, Rivaroxaban, Sotalol, and Indapamide) were analyzed during 200 ns MD simulations. The average root-mean-square deviation (RMSD) values along with standard deviation were calculated for all complexes between approximately 1.90 +/- 0.37 and 1.59 +/- 0.21 & Aring;. The average RMSD values of AChE-Trazodone and AChE-Rivaroxaban, respectively, were found to be 1.69 +/- 0.19 and 1.74 +/- 0.30 & Aring;. On the basis of in vitro findings, Trazodone (12.61 +/- 0.52 nM) showed 2.11-fold more inhibitory activity than donepezil (DNP). In vitro AChE activity of Rivaroxaban (26.82 +/- 0.51 nM) was found to be similar to DNP (26.67 +/- 0.56 nM). Frovatriptan, Eletriptan, Bupropion, Sotalol, and Indapamide had 1.84-, 1.70-, 1.67-, 1.29-, and 1.23-fold higher activity than tacrine. This study highlights the potency of the studied FDA-approved drugs to inhibit AChE for the treatment of AD through in silico and in vitro studies.
dc.description.sponsorshipanakkale Onsekiz Mart University Research Coordination Unit [TYL-2024-4743]
dc.description.sponsorshipThe authors thank Canakkale Onsekiz Mart University Research Coordination Unit for financial support. MS also thanks the Scientific and Technological Research Council of Turkiye (TUB & Idot;TAK) for the BIDEB 2210C scholarship program.
dc.identifier.doi10.1002/slct.202505605
dc.identifier.issn2365-6549
dc.identifier.issue48
dc.identifier.scopus2-s2.0-105025658343
dc.identifier.scopusqualityQ3
dc.identifier.urihttps://doi.org/10.1002/slct.202505605
dc.identifier.urihttps://hdl.handle.net/20.500.12428/34991
dc.identifier.volume10
dc.identifier.wosWOS:001645566300001
dc.identifier.wosqualityQ3
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.language.isoen
dc.publisherWiley-V C H Verlag Gmbh
dc.relation.ispartofChemistryselect
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.snmzKA_WOS_20260130
dc.subjectAChE inhibitor
dc.subjectAlzheimer's disease
dc.subjectdrug repurposing
dc.subjectin vitro
dc.subjectMD simulation
dc.titleRepurposing of FDA-Approved Drugs as Acetylcholinesterase Inhibitors for Alzheimer's Disease: A Combined In Silico and In Vitro Evaluation and Structure-Activity Relationship
dc.typeArticle

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