Publication:
Thioether-substituted benzimidazolium salts: Synthesis, characterization, crystal structure, and their inhibitory properties against acetylcholinesterase and xanthine oxidase

dc.contributor.authorYavuz, Kemal
dc.contributor.authorSen, Betül
dc.contributor.authorTaşkın-Tok, Tuğba
dc.contributor.authorAktas, Aydın
dc.contributor.authorAteş, Burhan
dc.contributor.authorAygün, Muhittin
dc.contributor.authorGök, Yetkin
dc.contributor.buuauthorOSMAN, BİLGEN
dc.contributor.buuauthorNoma, Samir Abbas Ali
dc.contributor.buuauthorNOMA, Samir Abbas Ali
dc.contributor.departmentFen Edebiyat Fakültesi
dc.contributor.departmentKimya Ana Bilim Dalı
dc.contributor.researcheridABF-4791-2020
dc.contributor.researcheridABH-1773-2021
dc.date.accessioned2024-11-28T11:26:43Z
dc.date.available2024-11-28T11:26:43Z
dc.date.issued2023-05-10
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.
dc.description.sponsorshipInonu Üniversitesi FOA-2020 -2240
dc.description.sponsorshipDokuz Eylül Üniversitesi 2010.KB.FEN.13
dc.identifier.doi10.1016/j.molstruc.2023.135640
dc.identifier.issn0022-2860
dc.identifier.urihttps://doi.org/10.1016/j.molstruc.2023.135640
dc.identifier.urihttps://hdl.handle.net/11452/48647
dc.identifier.volume1287
dc.identifier.wos001009119800001
dc.indexed.wosWOS.SCI
dc.language.isoen
dc.publisherElsevier
dc.relation.journalJournal Of Molecular Structure
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.subjectUric-acid
dc.subjectMechanism
dc.subjectAcetylcholinesterase
dc.subjectBenzimidazolium
dc.subjectPharmacodynamics study
dc.subjectThioether
dc.subjectXanthine oxidase
dc.subjectX-ray crystallography
dc.subjectScience & technology
dc.subjectPhysical sciences
dc.subjectChemistry, physical
dc.subjectChemistry
dc.titleThioether-substituted benzimidazolium salts: Synthesis, characterization, crystal structure, and their inhibitory properties against acetylcholinesterase and xanthine oxidase
dc.typeArticle
dspace.entity.typePublication
local.contributor.departmentFen Edebiyat Fakültesi/Kimya Ana Bilim Dalı
relation.isAuthorOfPublicationb696c48b-ee92-4822-be1f-c84f4fe0e3a6
relation.isAuthorOfPublication08ae8d1b-5dad-4ab3-8186-7723e086d163
relation.isAuthorOfPublication.latestForDiscoveryb696c48b-ee92-4822-be1f-c84f4fe0e3a6

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