Person: İÇSEL YILMAZ, CEYDA
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İÇSEL YILMAZ
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Publication Novel 5-fluorouracil complexes of Zn(II) with pyridine-based ligands as potential anticancer agents(Royal Soc Chemistry, 2022-03-02) İcsel, Ceyda; Yılmaz, Veysel T.; Aygün, Muhittin; Erkısa, Merve; Ulukaya, Engin; İÇSEL YILMAZ, CEYDA; YILMAZ, VEYSEL TURAN; Fen Edebiyat Fakültesi; Kimya Bölümü; 0000-0002-2849-3332; AAI-3342-2021; L-7238-2018A 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)]center dot H2O (3), [Zn(5-FU)(2)(bpyma)]center dot 2H(2)O (4) and [Zn(5-FU)(2)(terpy)]center dot 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 gamma-H2AX, thus contributing to its remarkable anticancer activity.Publication Cytotoxic platinum(II) complexes derived from saccharinate and phosphine ligands: synthesis, structures, DNA cleavage, and oxidative stress-induced apoptosis(Springer, 2019-10-26) İçsel, Ceyda; Yılmaz, Veysel T.; Cevatemre, Buse; Aygün, Muhittin; Ulukaya, Engin; İÇSEL YILMAZ, CEYDA; YILMAZ, VEYSEL TURAN; Fen Edebiyat Fakültesi; Kimya Bölümü; 0000-0002-2849-3332; L-7238-2018; AAI-3342-2021A series of the structurally related platinum(II) saccharinate (sac) complexes with alkylphenylphosphines, namely cis-[Pt(sac)(2)(PPh2Me)(2)]center dot DMSO (1), cis-[Pt(sac)(2)(PPhMe2)(2)] (2), cis-[Pt(sac)(2)(PPh2Et)(2)] (3), and cis-[Pt(sac)(2)(PPhEt2)(2)]center dot 2DMSO (4), were synthesized and fully characterized; their structures were determined by X-ray crystallography. All the complexes were investigated for their anticancer potentials on three human cancer cells including A549 (lung), MCF-7 (breast), and HCT116 (colon) in addition to a noncancerous human bronchial epithelial cells (BEAS-2B). Specifically, 1 and 3 showed significant cytotoxic effects against MCF-7 and HCT116 cell lines in comparison to cisplatin, and were considered as the most potent ones in the series. The cytotoxic complexes were found to cleave DNA efficiently. In addition, the binding interactions of the complexes with DNA were confirmed by enzyme inhibition and molecular docking studies. Complexes 1 and 3 were capable of inducing apoptosis and arrested the cell cycle at the DNA synthesis (S) phase in MCF-7 cells. Furthermore, 1 and 3 caused the excessive generation of reactive oxygen species (ROS), leading to mitochondrial dysfunction and double-strand DNA breaks.Publication Synthesis, characterization and crystal structures of platinum(II) saccharinate complexes with 1,5-cyclooctadiene(TÜBİTAK, 2020-04-24) İcsel, Ceyda; İÇSEL YILMAZ, CEYDA; Fen Edebiyat Fakültesi; Kimya Bölümü; 0000-0002-2717-2430; AAI-3342-2021Two new platinum(II) complexes, namely [PtCl(sac)(COD)] (1) and [Pt(sac)(2) (COD)] (2) (sac = saccharinate and COD = 1,5-cyclooctadiene), were synthesized and characterized by elemental analysis, IR, NMR, ESI-MS spectroscopic and thermal analysis (TG/DTA) methods. The platinum(II) complexes were prepared from the reaction of [PtCl2 (COD)] with Na(sac)center dot 2H(2)O. The addition of the sac ligand resulted in the replacement of 1 and 2 chlorido ligands in [PtCl2 (COD)] to yield 1 and 2, respectively. The structures of the complexes were determined by single crystal X-ray diffraction and showed a distorted square planar coordination geometry around platinum(II). COD acted as a p-donor ligand, while sac was N-coordinated in both complexes. The TG/DTA data indicated that both complexes were thermally stable up to 220 degrees C in air and their thermal decompositions yielded Pt as a final product. Complexes 1 and 2 were also designed as possible precursors to synthesize new mixed-ligand platinum(II) sac complexes in a one-pot reaction.