Browsing by Author "Acilan, Ceyda"
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Article Citation Count: 6A platinum blue complex exerts its cytotoxic activity via DNA damage and induces apoptosis in cancer cells(Wiley, 2017) Özalp Yaman, Şeniz; Ozalp-Yaman, Seniz; Celik, Gokalp; Salem, Safia; Bagci-Onder, Tugba; Senbabaoglu, Filiz; Acilan, Ceyda; Chemical EngineeringHere, we describe the characteristics of a Pt-blue complex [Pt-4(2-atp)(8)(H2O)(OH)] (2-atp: 2-aminothiophenol) as a prodrug for its DNA-binding properties and its use in cancer therapy. The nature of the interaction between the Pt-blue complex and DNA was evaluated based on spectroscopic measurements, the electronic absorption spectra, thermal behavior, viscosity, fluorometric titration, and agarose gel electrophoresis. Our results suggested that the compound was able to partially intercalate DNA and appeared to induce both single- and double-stranded breaks (DBS) on DNA in vitro, but no DSBs in cells. The ability of the compound to induce DNA damage was dependent on reactive oxygen species (ROS) in vitro. There was also elevated formation of ROS and SOD expression in response to drug treatment in cell culture. The complex was found to be more cytotoxic to cancer cells in comparison with noncancer controls using WST-1 assay. The mean of cell death was determined to be apoptosis as assessed via biochemical, morphological, and molecular observations, including DNA condensation/fragmentation analysis, live cell imaging microscopy, TUNEL analyses, and increase in the levels of pro-apoptotic genes such as Bag3, Bak, Bik, Bmf, and Hrk. Hence, the Pt-blue complex under study grants premise for further studies.Article Citation Count: 4Radicalic cleavage pathway and DNA docking studies of novel chemotherapic platinum agent of 5,6-di-2-ithienyl-2,3-dihydropyrazine(Pergamon-elsevier Science Ltd, 2019) Kayı, Hakan; Abdusalam, Mohamed Musbah; Özalp Yaman, Şeniz; Kayi, Hakan; Ozalp-Yaman, Seniz; Chemical EngineeringA new Pt(II) complex of the general formula ([PtCl2(L)]center dot H2O), where L is 5,6-di-2-thienyl-2,3-dihydropyrazine is synthesized as a potential antitumor agent and its structure is elucidated using a variety of physical and chemical procedures. DNA attaching ability of the complex is studied spectroscopically. UV and fluorometric titration, viscometric measurements and thermal decomposition studies agreed that two binding mode of actions, covalent and non-covalent bindings, are possible simultaneously. DNA helix cleavage studies clearly indicated OH center dot radical pathway in the presence of the reducing agent. Quantum mechanical calculations are carried out to call the minimum energy structures of the ligand and the complex, and to determine the FTIR, H-1 NMR and UV-Vis spectra using the density functional theory (DFT) at the B3LYP/LANL2DZ level of theory. Calculated geometrical parameters for the complex indicated a square-planar structure around the metallic center through the dithiopyridyl ring and two chlorine atoms. The minimum energy structure of the complex obtained from DFT conformational analysis is used in docking studies to investigate complex-DNA binding mechanisms. The complex interacts with DNA through three different mechanisms, namely, intercalation, covalent and electrostatic interaction. The most stable mode of interaction with lowest binding energy (-333.6 kcal/mol) was intercalation mode. Comparisons between theoretical and experimental findings are performed and a good agreement is obtained. (C) 2019 Elsevier Ltd. All rights reserved.