Benzoxazole Derivatives as Dual p38α Mitogen-Activated Protein Kinase and Acetylcholinesterase Inhibitors: Design, Synthesis, and Evaluation for Alzheimer's Disease and Cancer Therapy

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dc.contributor.authorZoatier, Bayan
dc.contributor.authorYildiztekin, Gizem
dc.contributor.authorAlagoz, Mehmet Abdullah
dc.contributor.authorHepokur, Ceylan
dc.contributor.authorDilek, Esra
dc.contributor.authorAlgul, Oztekin
dc.date.accessioned2026-04-04T13:37:41Z
dc.date.available2026-04-04T13:37:41Z
dc.date.issued2025
dc.departmentİnönü Üniversitesi
dc.description.abstractAlzheimer's disease (AD), the most prevalent form of dementia, leads to progressive cognitive decline due to pathological hallmarks including amyloid plaques, neurofibrillary tangles, synaptic loss, neuroinflammation, and neuronal cell death, highlighting the urgent need for multitarget therapeutic strategies. The p38 alpha mitogen-activated protein kinase (p38 alpha MAPK) pathway is a key regulator of neuroinflammation and has been implicated in AD pathogenesis. Additionally, dysregulation of p38 alpha MAPK is associated with tumorigenesis, making it a promising target for both neurodegenerative and proliferative diseases. In this article, a series of benzoxazole derivatives is designed and synthesized to evaluate their dual inhibitory potential against p38 alpha MAPK and acetylcholinesterase (AChE), aiming for a multifaceted therapeutic approach to AD. A total of 31 compounds are synthesized and assessed for their antiproliferative activity, p38 alpha MAPK inhibition, and AChE inhibitory effects. In vitro assays demonstrate that several compounds exhibit potent dual inhibition of p38 alpha MAPK and AChE, while molecular docking studies provide insights into their binding interactions within the active sites. These findings suggest that benzoxazole-based scaffolds offer a promising framework for the development of dual-acting inhibitors targeting both neuroinflammation and tumorigenesis. Further in vivo and mechanistic studies are warranted to explore their therapeutic potential.
dc.description.sponsorshipMersin University [2020-1-TP3-4028 BAP]
dc.description.sponsorshipThe authors would also like to thank Mersin University AdvancedTechnology Education, Research and Application Center (MEITAM) for their valuable assistance. This study was supported by 2020-1-TP3-4028 BAP Projects of Mersin University
dc.identifier.doi10.1002/cmdc.202500669
dc.identifier.issn1860-7179
dc.identifier.issn1860-7187
dc.identifier.issue22
dc.identifier.pmid41047159
dc.identifier.scopus2-s2.0-105017896259
dc.identifier.scopusqualityQ1
dc.identifier.urihttps://doi.org/10.1002/cmdc.202500669
dc.identifier.urihttps://hdl.handle.net/11616/109990
dc.identifier.volume20
dc.identifier.wosWOS:001586511500001
dc.identifier.wosqualityQ2
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherWiley-V C H Verlag Gmbh
dc.relation.ispartofChemmedchem
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.snmzKA_WOS_20250329
dc.subjectacetylcholinesterases
dc.subjectalzheimer disease
dc.subjectbenzoxazoles
dc.subjectmitogen-activated protein kinases
dc.subjectmolecular docking
dc.subjectp38 alpha
dc.titleBenzoxazole Derivatives as Dual p38α Mitogen-Activated Protein Kinase and Acetylcholinesterase Inhibitors: Design, Synthesis, and Evaluation for Alzheimer's Disease and Cancer Therapy
dc.typeArticle

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