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

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dc.authorid0000-0002-3087-5145
dc.authorid0000-0003-3276-1413
dc.authorid0000-0003-4927-2405
dc.authorid0000-0001-8705-6522
dc.authorid0000-0002-2882-6811
dc.authorid0000-0001-7845-0288
dc.contributor.authorBulut, Zafer
dc.contributor.authorAbul, Nurgul
dc.contributor.authorPoslu, Ayse Halic
dc.contributor.authorGulcin, Ilhami
dc.contributor.authorEce, Abdulilah
dc.contributor.authorErcag, Erol
dc.contributor.authorKoz, Gamze
dc.date.accessioned2026-02-12T21:05:06Z
dc.date.available2026-02-12T21:05:06Z
dc.date.issued2023
dc.departmentBursa Teknik Üniversitesi
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, H-1 NMR, C-13 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 K-i 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 K-i 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 K-i 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. (c) 2023 Elsevier B.V. All rights reserved.
dc.description.sponsorshipScientific and Technologi-cal Research Council of Turkey [119Z876]; Bursa Technical University Scientific Research Fund [210Y002]
dc.description.sponsorshipFunding This work was supported by the Scientific and Technologi-cal Research Council of Turkey , [Grand Numbers 119Z876] and Bursa Technical University Scientific Research Fund [Grand Num-bers 210Y002]
dc.identifier.doi10.1016/j.molstruc.2023.135047
dc.identifier.issn0022-2860
dc.identifier.issn1872-8014
dc.identifier.scopus2-s2.0-85147095740
dc.identifier.scopusqualityQ1
dc.identifier.urihttps://doi.org/10.1016/j.molstruc.2023.135047
dc.identifier.urihttps://hdl.handle.net/20.500.12885/6801
dc.identifier.volume1280
dc.identifier.wosWOS:000964028200001
dc.identifier.wosqualityQ2
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.language.isoen
dc.publisherElsevier
dc.relation.ispartofJournal of Molecular Structure
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.snmzKA_WoS_20260212
dc.subjectBenzylic amines
dc.subjectUracil
dc.subjectReductive amination
dc.subjectAcetylcholinesterase
dc.subjectCarbonic anhydrase
dc.subjectMolecular docking
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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