Thioether-substituted Benzimidazolium Salts: Synthesis, Characterization, Crystal Structure, and Their Inhibitory Properties Against Acetylcholinesterase and Xanthine Oxidase

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dc.authoridTASKIN TOK, Tugba/0000-0002-0064-8400
dc.authoridAktaş, Aydın/0000-0001-8496-6782
dc.authoridAygün, Muhittin/0000-0001-9670-9062
dc.authorwosidTASKIN TOK, Tugba/A-8885-2016
dc.authorwosidAktaş, Aydın/J-6194-2019
dc.authorwosidAygün, Muhittin/E-9590-2011
dc.contributor.authorYavuz, Kemal
dc.contributor.authorNoma, Samir Abbas Ali
dc.contributor.authorSen, Betuel
dc.contributor.authorTaskin-Tok, Tugba
dc.contributor.authorAktas, Aydin
dc.contributor.authorAtes, Burhan
dc.contributor.authorOsman, Bilgen
dc.date.accessioned2024-08-04T20:53:41Z
dc.date.available2024-08-04T20:53:41Z
dc.date.issued2023
dc.departmentİnönü Üniversitesien_US
dc.description.abstractThe sulfurous compounds are known as organosulfur, which has been associated with numerous biological activities in both natural products and synthetic organic compounds. In this work, we present the synthesis of a series of 4-(methylthio)benzyl substituted benzimidazolium salts. All compounds were characterized using NMR (1H and 13C) and FTIR spectroscopic methods as well as an elemental analysis technique. The molecular and crystal structures of the compound 1a were determined by X-ray crystallography revealing that the compound crystallized in the trigonal space group R-3. Enzyme inhibition studies demonstrated that a new series of sulfurous compounds precursors were highly potent inhibitors for xanthine oxidase (XO) and acetylcholinesterase (AChE) enzyme. The IC50 values were found in the range of 0.548 +/- 0.033 to 0.725 +/- 0.043 mu M for XO promising strategy for the treatment from gout disease, while IC50 values were found in the range 0.813 +/- 0.076 to 1.149 +/- 0.072 mu M toward AChE as the key enzyme promising strategy for the treatment of neurological disorders such as Alzheimer's disease (AD). Furthermore, pharmacodynamics studies prove the binding interaction patterns, structural orientations and drug potential of sulfide derivatives in the binding sites of xanthine oxidase (XO) and acetylcholinesterase (AChE) enzymes. Potential inhibitors (compounds 1d-f) were compared with standard compounds allopurinol (for XO) and donepezil (for AChE). Compared to the positive compound of target XO, the 4-vinylbenzyl group of potential compound 1f and the 4-methylbenzyl group of compound le more effectively formed electrostatic and hydrophobic interactions with the target's interaction site. While donepezil as standard compound interacts only at the peripheral anionic site of AChE, the related compounds interact with both regions (PAS and CAS sites) of the same target. These compounds were placed at the active sites of the respective targets by molecular docking method using AutoDock software. Binding energy, binding modes and interaction types were used to evaluate the series of 4-(methylthio)benzyl substituted benzimidazolium salts's ability to bind to each target. Binding energy lower than zero remarks spontaneous binding, and equal and/or lower than -5 kcal/mol remarks good binding. Besides XO, the related compounds show higher activity against the AChE enzyme. They can also be analyzed as strong candidate compounds in biological studies of related enzymes.en_US
dc.description.sponsorshipInonu University Research Fund [FOA-2020 -2240]; Dokuz Eyluel University [2010.KB.FEN.13]en_US
dc.description.sponsorshipThe authors thank Esin Aki Yalcin and the research group for technical assistance. This study was financially supported by Inonu University Research Fund (Project Code: FOA-2020 -2240) . Dokuz Eyluel University for the use of the Oxford Rigaku Xcalibur Eos Diffractometer (purchased under University Research Grant No: 2010.KB.FEN.13) is also greatly acknowledged.en_US
dc.identifier.doi10.1016/j.molstruc.2023.135640
dc.identifier.issn0022-2860
dc.identifier.issn1872-8014
dc.identifier.scopus2-s2.0-85158863698en_US
dc.identifier.scopusqualityQ2en_US
dc.identifier.urihttps://doi.org/10.1016/j.molstruc.2023.135640
dc.identifier.urihttps://hdl.handle.net/11616/101340
dc.identifier.volume1287en_US
dc.identifier.wosWOS:001009119800001en_US
dc.identifier.wosqualityQ2en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.language.isoenen_US
dc.publisherElsevieren_US
dc.relation.ispartofJournal of Molecular Structureen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectAcetylcholinesteraseen_US
dc.subjectBenzimidazoliumen_US
dc.subjectPharmacodynamics studyen_US
dc.subjectThioetheren_US
dc.subjectXanthine oxidaseen_US
dc.subjectX-ray crystallographyen_US
dc.titleThioether-substituted Benzimidazolium Salts: Synthesis, Characterization, Crystal Structure, and Their Inhibitory Properties Against Acetylcholinesterase and Xanthine Oxidaseen_US
dc.typeArticleen_US

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