The Cytotoxicity Profile, Apoptosis Mechanism, and Molecular Docking Studies of a Series of Benzimidazolium Derivative Morpholine-Substituted Ag(I) Heterocyclic Carbene Complexes

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dc.authoridYıldırım, Işıl/0000-0002-3027-6054
dc.authoridAktaş, Aydın/0000-0001-8496-6782
dc.authoridKUTLU, Turkan/0000-0002-1501-9930
dc.authoridTASKIN TOK, Tugba/0000-0002-0064-8400
dc.authorwosidYıldırım, Işıl/AAJ-6588-2020
dc.authorwosidAktaş, Aydın/J-6194-2019
dc.authorwosidKUTLU, Turkan/ABI-2589-2020
dc.authorwosidDikmen, Miris/IRZ-0516-2023
dc.authorwosidTASKIN TOK, Tugba/A-8885-2016
dc.contributor.authorKutlu, Tuerkan
dc.contributor.authorYildirim, Isil
dc.contributor.authorDikmen, Miris
dc.contributor.authorTok, Tugba Taskin
dc.contributor.authorAktas, Aydin
dc.contributor.authorGok, Yetkin
dc.date.accessioned2024-08-04T20:53:40Z
dc.date.available2024-08-04T20:53:40Z
dc.date.issued2023
dc.departmentİnönü Üniversitesien_US
dc.description.abstractThe main problems experienced in treatment with anticancer drugs are undesirable side effects, and toxicity. Minimal side effects for new anticancer compounds may be met due to enhanced efforts to clarify the compound's mechanisms of action. Therefore, we aimed to investigate whether or the cytotoxic effect and apoptosis mechanism of a series Ag(I)NHC complexes on non-small cell lung cancer cell line (A549) and normal lung fibroblast cell line (CCD-19Lu) in this study. The cytotoxicity was determined by using the MTT method, and apoptotic effects were detected by cell cycle, annexin-V/propidium iodide (PI) staining and cell cycle, caspase-3, mitochondrial membrane potential analysis. Molecular docking studies were performed using in silico ADMET analysis, and molecular docking information on the compounds was gained using the DS 3.5 software subprotocol. All the time, the cytotoxic effect of silver compounds was monitored for 24 h in comparison to cisplatin. The apoptotic effect of these compounds increased in cancer cells as compared to normal cells. Complex 3b exhibited the highest cytotoxic activity on cancer cell in 24 and 72 h, but complex 3a exhibited the highest cytotoxic activity on cancer cell s in 48 h. Moreover, all Ag(I)NHC complexes exhibited significant statistical difference depending on the increase in concentration on cancer cells, and all compounds induced apoptosis associated with distributing of membrane polarization and stopping the cell cycle in phase G1 and the caspase-3 activity. Caspase-3 activity of the new Ag(I)NHC compounds showed 8.3 to 17.6-fold increase compared the untreated cells. The loss of mitochondrial membrane potential indicated that JC-1 assay results were 16.9 to17.2-fold higher than normal cells in Ag(I)NHC compounds and 11.3-fold higher her in cisplatin. In addition, molecular docking studies were executed on the Ag(I)NHC complexes, and cisplatin estimate that the binding modes towards the EGFR kinase. Because epidermal growth factor receptor (EGFR) is expressed highly in a great number of epithelial tumors. These findings suggested that Ag(I)NHC complexes exhibited anticancer activity and may be considered to have a new therapeutic potential for human non-small cell lung cancer cell treatment.en_US
dc.description.sponsorshipInonu University Research Project Unit [I. U. BAP 2016/166]en_US
dc.description.sponsorshipThis study was financially supported by the Inonu University Research Project Unit (Project No. the I. U. BAP 2016/166).en_US
dc.identifier.doi10.1007/s11094-023-02846-9
dc.identifier.endpage28en_US
dc.identifier.issn0091-150X
dc.identifier.issn1573-9031
dc.identifier.issue1en_US
dc.identifier.scopus2-s2.0-85153076090en_US
dc.identifier.scopusqualityQ4en_US
dc.identifier.startpage10en_US
dc.identifier.urihttps://doi.org/10.1007/s11094-023-02846-9
dc.identifier.urihttps://hdl.handle.net/11616/101303
dc.identifier.volume57en_US
dc.identifier.wosWOS:000972349400001en_US
dc.identifier.wosqualityQ4en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.language.isoenen_US
dc.publisherSpringeren_US
dc.relation.ispartofPharmaceutical Chemistry Journalen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectAg(I)NHCen_US
dc.subjectapoptosisen_US
dc.subjectbenzimidazoliumen_US
dc.subjectnon-small lung cancer cellen_US
dc.subjectmorpholineen_US
dc.subjectmolecular dockingen_US
dc.subjectEGFRen_US
dc.subjectflow cytometryen_US
dc.titleThe Cytotoxicity Profile, Apoptosis Mechanism, and Molecular Docking Studies of a Series of Benzimidazolium Derivative Morpholine-Substituted Ag(I) Heterocyclic Carbene Complexesen_US
dc.typeArticleen_US

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