Azole derivatives inhibit wildtype butyrylcholinesterase and its common mutants

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dc.authoridKarakurt, Arzu/0000-0003-2209-0871
dc.authoridAKKAYA, Didem/0000-0002-0711-951X
dc.authoridSARI, SUAT/0000-0002-8248-4218
dc.authorwosidKarakurt, Arzu/ABH-9340-2020
dc.authorwosidÖnder, Seda/JYQ-5629-2024
dc.authorwosidAKKAYA, Didem/AAJ-7644-2021
dc.authorwosidSARI, SUAT/A-5249-2017
dc.contributor.authorSari, Suat
dc.contributor.authorOnder, Seda
dc.contributor.authorAkkaya, Didem
dc.contributor.authorSabuncuoglu, Suna
dc.contributor.authorZengin, Merve
dc.contributor.authorBarut, Burak
dc.contributor.authorKarakurt, Arzu
dc.date.accessioned2024-08-04T20:53:41Z
dc.date.available2024-08-04T20:53:41Z
dc.date.issued2023
dc.departmentİnönü Üniversitesien_US
dc.description.abstractAzoles, which have been used for antifungal chemotherapy for decades, have recently been of interest for their efficacy against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). There is little known about the potential of azoles against BChE, however there is none regarding their inhibitory effects against mutants of BChE. In the current study, an azole library of 1-aryl-2-(1H-imidazol-1-yl)ethanol/ethanone oxime esters were tested against AChE and BChE, which yielded derivates more potent than the positive control, galantamine, against both isoforms. Kinetic analyses were performed for wildtype and mutant (A328F and A328Y) inhibition for the two most potent BChE inhibitors, pivalic and 3-bezoylpropanoic acid esters of 2-(1H-imidazol-1-yl)-1-(2-naphthyl)ethanol, which were found to have great affinity to the wildtype and mutant BChE types with K-i values as low as 0.173 +/- 0.012 mu M. The compounds were identified to show linear competitive or mixed type inhibition. Molecular modeling confirmed these kinetic data and provided further insights regarding molecular basis of BChE inhibition by the active derivatives. Thus, current study suggests new azole derivatives with promising cholinesterase inhibitory effects and reveals the first set of information to promote our understanding for the inhibitory behavior of this class against the mutant BChE forms.en_US
dc.description.sponsorshipHacettepe Universitesien_US
dc.description.sponsorshipHacettepe Universitesien_US
dc.identifier.doi10.1002/ddr.22071
dc.identifier.endpage1028en_US
dc.identifier.issn0272-4391
dc.identifier.issn1098-2299
dc.identifier.issue5en_US
dc.identifier.pmid37154110en_US
dc.identifier.scopus2-s2.0-85158109838en_US
dc.identifier.scopusqualityQ2en_US
dc.identifier.startpage1018en_US
dc.identifier.urihttps://doi.org/10.1002/ddr.22071
dc.identifier.urihttps://hdl.handle.net/11616/101338
dc.identifier.volume84en_US
dc.identifier.wosWOS:000982414400001en_US
dc.identifier.wosqualityQ2en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherWileyen_US
dc.relation.ispartofDrug Development Researchen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectacetylcholinesteraseen_US
dc.subjectbutyrylcholinesteraseen_US
dc.subjectenzyme kineticsen_US
dc.titleAzole derivatives inhibit wildtype butyrylcholinesterase and its common mutantsen_US
dc.typeArticleen_US

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