Synthesis and biological activities of pyridine N-oxide bearing 5-aminoisoxazoles as potential acetylcholinesterase and monoamine oxidase inhibitors for Alzheimerʼs disease

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dc.authorid0000-0001-5216-1226
dc.authorid0000-0002-0151-6266
dc.authorid0000-0002-4180-8423
dc.authorid0000-0003-4740-1138
dc.authorscopusid57214892019
dc.authorscopusid59148736200
dc.authorscopusid57191603559
dc.authorscopusid6603732582
dc.authorscopusid11540283300
dc.contributor.authorSaleh, Lange Yakubu
dc.contributor.authorÖzdemir, Soner
dc.contributor.authorSağlık, Begüm Nurpelin
dc.contributor.authorDöndaş, Hacı Ali
dc.contributor.authorAltuğ, Cevher
dc.date.accessioned2024-09-25T19:42:54Z
dc.date.available2024-09-25T19:42:54Z
dc.date.issued2024
dc.departmentBAİBÜ, Fen Edebiyat Fakültesi, Kimya Bölümüen_US
dc.description.abstractA series of ten novel pyridine N-oxide-bearing 5-aminoisoxazoles was efficiently synthesized in moderate yields by reacting 2-(cyanomethyl)pyridine 1-oxide with ?-chlorooximes, employing sodium ethoxide as a base. The synthesized compounds were verified with a variety of spectra. Subsequently, the inhibitory potency of compounds 4c, 4e, 4f, 4h, and 4i against AChE and BChE, primary targets in Alzheimer's disease, was assessed. In silico docking analyses were conducted to evaluate the interaction of compounds 4c, 4e, 4f, 4h, and 4i with AChE and MAO-B. Among the tested compounds, 4e and 4h demonstrated remarkable AChE inhibition, exhibiting IC50 values of (0.050 µM and 0.039 µM, respectively), comparable to the inhibition achieved by donepezil (IC50 = 0.020 µM). Additionally, compounds 4c, 4e, 4f, 4h, and 4i displayed potent MAO-A inhibition, with IC50 values of (0.203, 0.067, 0.083, 0.044, and 0.159 µM, respectively), surpassing the efficacy of moclobemide (IC50 = 6.061 µM). Compounds 4e, 4f, and 4h also inhibited MAO-B, with IC50 values of (0.076, 0.058, and 0.049 µM, respectively), close to the inhibitory effects of Selegiline (IC50 = 0.037 µM). Compound 4h emerged as a multi-target inhibitor, effectively inhibiting AChE, MAO-A, and MAO-B. These findings underscore the therapeutic potential of these novel compounds in the treatment of Alzheimer's disease, warranting further investigation into their clinical application. © 2024en_US
dc.description.sponsorshipNational Institutes of Health, NIH, (P41-GM103311); National Institutes of Health, NIHen_US
dc.identifier.doi10.1016/j.molstruc.2024.138667
dc.identifier.issn0022-2860
dc.identifier.scopus2-s2.0-85194490336en_US
dc.identifier.scopusqualityQ2en_US
dc.identifier.urihttps://doi.org/10.1016/j.molstruc.2024.138667
dc.identifier.urihttps://hdl.handle.net/20.500.12491/12350
dc.identifier.volume1313en_US
dc.indekslendigikaynakScopusen_US
dc.institutionauthorÖzdemir, Soner
dc.institutionauthorAltuğ, Cevher
dc.institutionauthorid0000-0003-4740-1138
dc.language.isoenen_US
dc.publisherElsevier B.V.en_US
dc.relation.ispartofJournal of Molecular Structureen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - İdari Personel ve Öğrencien_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.snmzYK_20240925en_US
dc.subjectAcetylcholinesteraseen_US
dc.subjectCycloaddition Reactionen_US
dc.subjectIsoxazole Derivativesen_US
dc.subjectMolecular Docking Studyen_US
dc.subjectMonoamine Oxidaseen_US
dc.subjectPyridine N-oxideen_US
dc.titleSynthesis and biological activities of pyridine N-oxide bearing 5-aminoisoxazoles as potential acetylcholinesterase and monoamine oxidase inhibitors for Alzheimerʼs diseaseen_US
dc.typeArticleen_US

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