5(6)-Benzoyl-Substituted Benzimidazoles and Their Benzimidazolium Salts: Design, Synthesis, Characterization, Crystal Structure, and Some Metabolic Enzymes Inhibition Properties

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dc.contributor.authorAktas, Aydin
dc.contributor.authorOzden, Eda Mehtap
dc.contributor.authorCelepci, Duygu Barut
dc.contributor.authorTaskin-Tok, Tugba
dc.contributor.authorEkti, Funda Sultan
dc.contributor.authorGulcin, Ilhami
dc.contributor.authorAygun, Muhittin
dc.date.accessioned2026-04-04T13:37:44Z
dc.date.available2026-04-04T13:37:44Z
dc.date.issued2025
dc.departmentİnönü Üniversitesi
dc.description.abstractHerein, the synthesis of 1-alkyl-5(6)-benzoyl-substituted benzimidazoles and their 1,3-bisalkylbenzimidazolium halide salts are presented and evaluated for some metabolic enzyme inhibition. All compounds were characterized using various spectroscopic techniques. Single-crystal XRD analysis was performed to determine the molecular structure of two compounds. The newly synthesized compounds exhibited significant inhibitory effects against acetylcholinesterase (AChE) and human carbonic anhydrase isoforms I and II (hCA I and hCA II) enzymes. These compounds demonstrated promising inhibition profiles, with Ki values ranging from 12.4 +/- 5.4 to 109.4 +/- 49.9 nM for hCA I, 23.1 +/- 11.2 to 115.0 +/- 17.9 nM for hCA II, and 0.7 +/- 0.3 to 4.4 +/- 1.0 nM for AChE. In comparison, the reference compound acetazolamide showed Ki values of 30.5 +/- 6.7 nM and 37.4 +/- 7.8 nM against hCA I and hCA II isoenzymes, respectively. Additionally, tacrine, a known AChE inhibitor, exhibited a Ki value of 5.1 +/- 2.7 nM. The dual inhibition of CA and AChE represents a valuable pharmacological approach with a wide range of therapeutic applications. The explanation and evaluation of the enzyme inhibition data obtained in line with the interactions of the synthesized compounds with hCA I, hCA II, and AChE enzymes were carried out by molecular docking studies. In particular, we focused on the three compounds (4e, 4f, and 4j for hCA I; 3g, 4f, and 4k for hCA II; and 4e, 4f, 4j, and 4l for AChE) with the highest potential activity with each enzyme. The physicochemical, ADME, drug-likeness, medicinal chemistry, and toxicity properties of the potential ligands were then predicted so that their drug candidate suitability for further studies is revealed.
dc.description.sponsorshipUniversity Research [2010.KB.FEN.13]
dc.description.sponsorshipThe authors thank the Inonu University Faculty of Science, Department of Chemistry, for the characterization of compounds. The authors thank Esin Ak & imath; Yalcin and the research group for technical assistance. The numerical calculations reported in this article were partially performed at TUBITAK ULAKBIM, High Performance and Grid Computing Center (TRUBA resources). The authors thank Dokuz Eyluel University for the use of the Oxford Rigaku Xcalibur Eos Diffractometer (purchased under University Research Grant No: 2010.KB.FEN.13), which is also greatly acknowledged.
dc.identifier.doi10.1002/ardp.70063
dc.identifier.issn0365-6233
dc.identifier.issn1521-4184
dc.identifier.issue7
dc.identifier.orcid0000-0002-9259-5704
dc.identifier.orcid0000-0002-0064-8400
dc.identifier.orcid0000-0001-5993-1668
dc.identifier.pmid40734240
dc.identifier.scopus2-s2.0-105012018397
dc.identifier.scopusqualityQ1
dc.identifier.urihttps://doi.org/10.1002/ardp.70063
dc.identifier.urihttps://hdl.handle.net/11616/110004
dc.identifier.volume358
dc.identifier.wosWOS:001544760900013
dc.identifier.wosqualityQ2
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherWiley-V C H Verlag Gmbh
dc.relation.ispartofArchiv Der Pharmazie
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.snmzKA_WOS_20250329
dc.subject5-benzoylbenzimidazolium salt
dc.subjectacetylcholinesterase
dc.subjectADMET
dc.subjectcarbonic anhydrase
dc.subjectmolecular docking
dc.subjectsingle-crystal X-ray diffraction
dc.title5(6)-Benzoyl-Substituted Benzimidazoles and Their Benzimidazolium Salts: Design, Synthesis, Characterization, Crystal Structure, and Some Metabolic Enzymes Inhibition Properties
dc.typeArticle

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