Structure-based inhibition of acetylcholinesterase and butyrylcholinesterase with 2-Aryl-6-carboxamide benzoxazole derivatives: synthesis, enzymatic assay, and in silico studies

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dc.authoridDemir, Yeliz/0000-0003-3216-1098
dc.authorwosidDemir, Yeliz/ABI-5719-2020
dc.contributor.authorKuzu, Burak
dc.contributor.authorAlagoz, M. Abdullah
dc.contributor.authorDemir, Yeliz
dc.contributor.authorGulcin, Ilhami
dc.contributor.authorBurmaoglu, Serdar
dc.contributor.authorAlgul, Oztekin
dc.date.accessioned2024-08-04T20:55:54Z
dc.date.available2024-08-04T20:55:54Z
dc.date.issued2024
dc.departmentİnönü Üniversitesien_US
dc.description.abstractAn important research topic is the discovery of multifunctional compounds targeting different disease-causing components. This research aimed to design and synthesize a series of 2-aryl-6-carboxamide benzoxazole derivatives that inhibit cholinesterases on both the peripheral anionic and catalytic anionic sides. Compounds (7-48) were prepared from 4-amino-3-hydroxybenzoic acid in three steps. The Ellman test, molecular docking with Maestro, and molecular dynamics simulation studies with Desmond were done (Schrodinger, 12.8.117). Compound 36, the most potent compound among the 42 new compounds synthesized, had an inhibitory concentration of IC50 12.62 nM for AChE and IC50 25.45 nM for BChE (whereas donepezil was 69.3 nM and 63.0 nM, respectively). Additionally, compound 36 had docking values of - 7.29 kcal/mol for AChE and - 6.71 kcal/mol for BChE (whereas donepezil was - 6.49 kcal/mol and - 5.057 kcal/mol, respectively). Furthermore, molecular dynamics simulations revealed that compound 36 is stable in the active gorges of both AChE (average RMSD: 1.98 & Aring;) and BChE (average RMSD: 2.2 & Aring;) (donepezil had average RMSD: 1.65 & Aring; and 2.7 & Aring;, respectively). The results show that compound 36 is a potent, selective, mixed-type dual inhibitor of both acetylcholinesterase and butyrylcholinesterase. It does this by binding to both the catalytically active and peripheral anionic sites of cholinesterases at the same time. These findings show that target compounds may be useful for establishing the structural basis for new anti-Alzheimer agents. [GRAPHICS] .en_US
dc.description.sponsorshipAtaturk Universityen_US
dc.description.sponsorshipNo Statement Availableen_US
dc.identifier.doi10.1007/s11030-024-10828-6
dc.identifier.issn1381-1991
dc.identifier.issn1573-501X
dc.identifier.pmid38554169en_US
dc.identifier.scopus2-s2.0-85189200727en_US
dc.identifier.scopusqualityQ2en_US
dc.identifier.urihttps://doi.org/10.1007/s11030-024-10828-6
dc.identifier.urihttps://hdl.handle.net/11616/101912
dc.identifier.wosWOS:001194827100003en_US
dc.identifier.wosqualityN/Aen_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherSpringeren_US
dc.relation.ispartofMolecular Diversityen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectBenzoxazoleen_US
dc.subjectEnzyme inhibitionen_US
dc.subjectAcetylcholinesteraseen_US
dc.subjectButyrylcholinesteraseen_US
dc.subjectMolecular docking and dynamic simulationen_US
dc.titleStructure-based inhibition of acetylcholinesterase and butyrylcholinesterase with 2-Aryl-6-carboxamide benzoxazole derivatives: synthesis, enzymatic assay, and in silico studiesen_US
dc.typeReview Articleen_US

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