Structural characterization and biological evaluation of uracil-appended benzylic amines as acetylcholinesterase and carbonic anhydrase I and II inhibitors

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dc.authorscopusid58083419700
dc.authorscopusid57216524546
dc.authorscopusid58083387700
dc.authorscopusid35509141500
dc.authorscopusid14009547900
dc.authorscopusid6508161441
dc.authorscopusid6505809121
dc.contributor.authorBulut, Z.
dc.contributor.authorAbul, N.
dc.contributor.authorPoslu, A.H.
dc.contributor.authorGülçin, İ.
dc.contributor.authorEce, A.
dc.contributor.authorErçağ, Erol
dc.contributor.authorKoz, Ö.
dc.contributor.authorErçağ, Erol
dc.date.accessioned2023-05-06T17:20:49Z
dc.date.available2023-05-06T17:20:49Z
dc.date.issued2023
dc.departmentFakülteler, Fen Edebiyat Fakültesi, Kimya Bölümü
dc.description.abstractA series of novel uracil-appended benzylic amines were synthesized through reductive amination with moderate to good yields (30–84% yields). In situ prepared 5-(arylidene)-6-aminouracils with the condensation reaction between 5,6-diamino-1,3-dimethyluracil and substituted salicylaldehydes were reduced by excess sodium borohydride. All of the compounds were characterized using FT-IR, 1H NMR, 13C NMR spectroscopy and elemental analysis. The inhibition abilities of novel uracil-appended benzylic amines (1–9) were evaluated against acetylcholinesterase (AChE) and human carbonic anhydrase I and II (hCA I and II) isoenzymes that are linked to some global disorders such as Alzheimer's disease (AD), epilepsy, diabetes and glaucoma. The compounds exhibited inhibition profiles with Ki values ranging from 2.28±0.41 nM to 5.25±0.75 nM for AChE, 36.10±5.22–110.31±54.81 nM for hCA I and 16.33±4.91–72.03±28.86 for hCA II. Tacrine was used as a reference inhibitor for AChE and exhibited a Ki value of 2.59±0.92 nM against the AChE enzyme. On the other hand, Acetazolamide was used as a standard inhibitor towards hCA I and hCA II isoforms with Ki values of 31.38±8.56 nM and 18.72±1.67 nM, respectively. The results of enzyme inhibition associated with some global metabolic diseases indicate that novel uracil-appended benzylic amines may have the potential to develop new drugs to treat some common diseases such as Alzheimer's disease (AD), epilepsy and glaucoma. Molecular docking simulations were conducted to explain the binding interactions of compounds with AChE, hCA I and hCA II. Pharmacokinetic profiles were predicted to be within the acceptable ranges. © 2023 Elsevier B.V.
dc.description.sponsorship210Y002; Türkiye Bilimsel ve Teknolojik Araştırma Kurumu, TÜBİTAK: 119Z876
dc.description.sponsorshipThis work was supported by the Scientific and Technological Research Council of Turkey , [Grand Numbers 119Z876 ] and Bursa Technical University Scientific Research Fund [Grand Numbers 210Y002 ]
dc.description.sponsorshipThe Scientific and Technological Research Council of Turkey (TÜBİTAK) and Bursa Technical University Scientific Research Fund are gratefully acknowledged. Bursa Technical University, Central Research Laboratory is acknowledged for elemental analysis. We thank Middle East Technical University Central Laboratory for HR-MS analysis.
dc.identifier.doi10.1016/j.molstruc.2023.135047
dc.identifier.issn0022-2860
dc.identifier.scopus2-s2.0-85147095740
dc.identifier.scopusqualityQ2
dc.identifier.urihttps://doi.org/10.1016/j.molstruc.2023.135047
dc.identifier.urihttps://hdl.handle.net/20.500.11776/11960
dc.identifier.volume1280
dc.identifier.wosWOS:000964028200001
dc.identifier.wosqualityQ2
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.institutionauthorErçağ, Erol
dc.language.isoen
dc.publisherElsevier B.V.
dc.relation.ispartofJournal of Molecular Structure
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.subjectAcetylcholinesterase
dc.subjectBenzylic amines
dc.subjectCarbonic anhydrase
dc.subjectMolecular docking
dc.subjectReductive amination
dc.subjectUracil
dc.subjectAromatic compounds
dc.subjectBinding energy
dc.subjectCondensation reactions
dc.subjectEnzyme inhibition
dc.subjectMolecular modeling
dc.subjectNeurodegenerative diseases
dc.subjectNeurology
dc.subjectNuclear magnetic resonance spectroscopy
dc.subjectOphthalmology
dc.subject6-aminouracil
dc.subjectAcetylcholinesterase
dc.subjectAlzheimers disease
dc.subjectBenzylic amines
dc.subjectBiological evaluation
dc.subjectMolecular docking
dc.subjectReductive amination
dc.subjectStructural characterization
dc.subjectSynthesised
dc.subjectUracil
dc.subjectAmines
dc.titleStructural characterization and biological evaluation of uracil-appended benzylic amines as acetylcholinesterase and carbonic anhydrase I and II inhibitors
dc.typeArticle

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