Novel 5-fluorouracil complexes of Zn(II) with pyridine-based ligands as potential anticancer agents

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dc.authoridEngin Ulukaya / 0000-0003-4875-5472en_US
dc.authorscopusidEngin Ulukaya / 6602927353
dc.authorwosidEngin Ulukaya / K-5792-2018
dc.contributor.authorİçsel, Ceyda
dc.contributor.authorYılmaz, Veysel T
dc.contributor.authorAygün, Muhittin
dc.contributor.authorErkısa, Merve
dc.contributor.authorUlukaya, Engin
dc.date.accessioned2022-04-06T05:46:48Z
dc.date.available2022-04-06T05:46:48Z
dc.date.issued2022en_US
dc.departmentİstinye Üniversitesi, Tıp Fakültesi, Temel Tıp Bilimleri Bölümüen_US
dc.description.abstractA series of novel Zn(II) complexes of 5-fluorouracilate (5-FU), namely [Zn(5-FU)2(bpy)] (1), [Zn(5-FU)2(phen)] (2), [Zn(5-FU)2(dpya)]·H2O (3), [Zn(5-FU)2(bpyma)]·2H2O (4) and [Zn(5-FU)2(terpy)]·H2O (5), were synthesized and structurally characterized by spectroscopic methods and X-ray crystallography. 5-FU was coordinated to Zn(II) via the deprotonated N3 site and also presented the N1 and N3 linkage isomerism in 4 and 5 due to its tautomerism. The antiproliferative activity of the complexes was studied against lung (A549), breast (MDA-MB-231), colon (HCT116) and prostate (DU145) cancer cell lines. Complexes 1, 4 and 5 except 2 and 3 showed potent growth inhibitory activity towards selected cancer cells. Remarkably, 4 was highly cytotoxic towards A549 and MDA-MB-231 cell lines, being more active than the clinical drugs cisplatin and 5-FU. In addition, 4 was not toxic to normal lung cells (BEAS-2B). The complex exhibited a significantly high affinity towards DNA as assessed by gel electrophoresis and DNA docking. The mechanistic studies of 4 in A549 cells indicated that the complex induced apoptotic cell death as evidenced via caspase 3/7 activity, Bcl2 inactivation, annexin V and DAPI/PI staining. 4 further elevated the levels of reactive oxygen species (ROS), depolarized mitochondria and enhanced the expression of ?-H2AX, thus contributing to its remarkable anticancer activity.en_US
dc.identifier.citationIcsel, C., Yilmaz, V. T., Aygün, M., & Ulukaya, E. (2022). Novel 5-fluorouracil complexes of Zn (II) with pyridine-based ligands as potential anticancer agents. Dalton Transactions.en_US
dc.identifier.doi10.1039/d1dt04070gen_US
dc.identifier.pmid35275157en_US
dc.identifier.scopus2-s2.0-85127028175en_US
dc.identifier.scopusqualityN/Aen_US
dc.identifier.urihttps://doi.org/10.1039/d1dt04070g
dc.identifier.urihttps://hdl.handle.net/20.500.12713/2618
dc.identifier.volume13en_US
dc.identifier.wosWOS:000767481100001en_US
dc.identifier.wosqualityQ1en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.institutionauthorUlukaya, Engin
dc.language.isoenen_US
dc.relation.ispartofDalton Transen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.titleNovel 5-fluorouracil complexes of Zn(II) with pyridine-based ligands as potential anticancer agentsen_US
dc.typeArticleen_US

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