1,4-Substituted 4-(1H)-pyridylene-hydrazone-type inhibitors of AChE, BuChE, and amyloid-beta aggregation crossing the blood-brain barrier

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dc.contributor.authorPrinz, Michaela
dc.contributor.authorParlar, Sulunay
dc.contributor.authorBayraktar, Gulsah
dc.contributor.authorAlptuzun, Vildan
dc.contributor.authorErciyas, Ercin
dc.contributor.authorFallarero, Adyary
dc.contributor.authorKarlsson, Daniela
dc.contributor.authorVuorela, Pia
dc.contributor.authorBurek, Malgorzata
dc.contributor.authorFoerster, Carola
dc.contributor.authorTurunc, Ezgi
dc.contributor.authorArmagan, Guliz
dc.contributor.authorYalcin, Ayfer
dc.contributor.authorSchiller, Carola
dc.contributor.authorLeuner, Kristina
dc.contributor.authorKrug, Manuel
dc.contributor.authorSotriffer, Christoph A.
dc.contributor.authorHolzgrabe, Ulrike
dc.date.accessioned2019-10-27T21:51:51Z
dc.date.available2019-10-27T21:51:51Z
dc.date.issued2013
dc.departmentEge Üniversitesien_US
dc.description.abstractGiven the fundamentally multifactorial character of Alzheimer's disease (AD), addressing more than one target for disease modification or therapy is expected to be highly advantageous. Here, following the cholinergic hypothesis, we aimed to inhibit both acetyl- and butyrylcholinesterase (AChE and BuChE) in order to increase the concentration of acetylcholine in the synaptic cleft. In addition, the formation of the amyloid p fibrils should be inhibited and already preformed fibrils should be destroyed. Based on a recently identified AChE inhibitor with a 1,4-substituted 4-(1H)-pyridylene-hydrazone skeleton, a substance library has been generated and tested for inhibition of AChE, BuChE, and fibril formation. Blood-brain barrier mobility was ensured by a transwell assay. Whereas the p-nitrosubstituted compound 18C shows an anti-AChE activity in the nanomolar range of concentration (IC50 = 90 nM), the bisnaphthyl substituted compound 20L was found to be the best overall inhibitor of AChE/BuChE and enhances the fibril destruction. (C) 2013 Elsevier B.V. All rights reserved.en_US
dc.description.sponsorshipEge University Scientific Research Project CouncilEge University [10/ECZ/012]en_US
dc.description.sponsorshipThis study was partially supported by Ege University Scientific Research Project Council (Project number: 10/ECZ/012). The help of Raphael Dives in carrying out the pK<INF>a</INF> calculations is gratefully acknowledged.en_US
dc.identifier.doi10.1016/j.ejps.2013.04.024en_US
dc.identifier.endpage613en_US
dc.identifier.issn0928-0987
dc.identifier.issn1879-0720
dc.identifier.issue4en_US
dc.identifier.pmid23643737en_US
dc.identifier.startpage603en_US
dc.identifier.urihttps://doi.org/10.1016/j.ejps.2013.04.024
dc.identifier.urihttps://hdl.handle.net/11454/47331
dc.identifier.volume49en_US
dc.identifier.wosWOS:000322751900019en_US
dc.identifier.wosqualityQ2en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherElsevier Science Bven_US
dc.relation.ispartofEuropean Journal of Pharmaceutical Sciencesen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectAlzheimeren_US
dc.subjectAcetylcholinesterase (AChE)en_US
dc.subjectButyrylcholinesterase (BuChE)en_US
dc.subjectAmyloid betaen_US
dc.subjectThioflavin Ten_US
dc.title1,4-Substituted 4-(1H)-pyridylene-hydrazone-type inhibitors of AChE, BuChE, and amyloid-beta aggregation crossing the blood-brain barrieren_US
dc.typeArticleen_US

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