Master Degree / Yüksek Lisans Tezleri

Permanent URI for this collectionhttps://hdl.handle.net/11147/3008

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2016 - 20194

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Publisher: search.filters.publisher.Izmir Institute of TechnologySubject: search.filters.subject.Cancer drugs

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Now showing 1 - 4 of 4
  • Master Thesis
    Studies Toward the Synthesis of Novel Mdm2 Inhibitor Candidates
    (Izmir Institute of Technology, 2018) Dilek, Fikrican; Çağır, Ali; Çağır, Ali; 04.01. Department of Chemistry; 04. Faculty of Science; 01. Izmir Institute of Technology
    Protein protein interactions are valuable targets to discover novel anticancer agents. One of these is the p53-MDM2 interaction. In one of these interaction MDM2 protein inhibits p53 protein and may cause cancer. New drugs that inhibit this interaction are important for the treatment of cancer. One class of these anticancer agents are morpholinone derivative. In this study, it is aimed to synthesize new morpholinone derivatives. (R)-2-amino-2-(4-chlorophenyl)acetic acid was used as starting material for the synthesis. The first step was a trityl protection of amine with trityl chloride. Trityl protected amino acid was first reduced to N-Trt amino alcohol with LiAlH4 then oxidized to aldehyde by using Dess-Martin periodinane. The resulting aldehyde was reacted with 3-chlorophenylmagnesium bromide. This part of the synthesis was performed successfully. Then addition of methyl fumarate to this Grignard product was studied by a coupling reagents such as HATU. All attempts were failed. Then trityl group was removed by TFA and successfully coupled with methyl fumarate by using HATU. All cyclization reactions in the presence of a base like hydroxide, alkoxide or NaH to form morpholinone skeleton was failed. The cyclization reaction with the potassim carbonate in alcohol was successful and the morpholinone skeleton was formed.
  • Master Thesis
    Design and Preparation of Alkali Liposomes for Drug Delivery
    (Izmir Institute of Technology, 2019) Güven, Hatice; Özdemir, Ekrem; Özdemir, Ekrem; Altun, Zekiye Sultan; 03.02. Department of Chemical Engineering; 03. Faculty of Engineering; 01. Izmir Institute of Technology
    Cancer is one of the deadliest diseases among other illnesses as an uncontrolled cell division. Liposomal technology has commonly been used in cancer therapy. Chemotherapeutical drugs, genetic materials, different imaging agents can be carried with liposomes. They are preferred by several important characteristics that selective passive targeting of tumors, increased stability and therapeutic index (reducing toxicity) via encapsulation and increased circulation life times with size adjustments. One of the indicator in cell cycle is intracellular pH. The aim of this study is to produce PEGylated alkali liposomes to provide cellular uptake in cancer cells and prevent cell division by changing of intracellular pH. Combination of liposomal technology and alkaline therapy in cancer cells may lead to the development of therapeutic strategies without using any drug to overcome chemoresistance and cell proliferation. For this purpose, alkali liposomes containing sodium carbonate (Na2CO3) solution were prepared and tested their effects on 4T1 breast cancer cell lines in vitro. The cell viabilities were evaluated using trypan blue and WST-1 methods. Pictures were taken for cancer cells to differentiate live and dead cells under different alkali liposome conditions for 5 days. It was found that cell medium containing alkali liposomes up to 3% didn’t affect cell growth. However, cell medium containing alkali liposomes greater than 7% significantly affected the 4T1 breast cancer cell growth and decreased the cell viability to about 40%. It was concluded that PEGylated alkali liposomes were prepared different concentrations to decrease or stop cell division of 4T1 breast cancer cell lines in vitro.
  • Master Thesis
    Synthesis of Molecularly Imprinted Polymers as Selective Solid Phase Extraction Sorbents for Anticancer Drugs Prior To Chromatographic Determination
    (Izmir Institute of Technology, 2018) Özdemir, Anıl; Eroğlu, Ahmet Emin; Eroğlu, Ahmet E.; 04.01. Department of Chemistry; 04. Faculty of Science; 01. Izmir Institute of Technology
    In recent years, the number of usage of chemotherapic drugs has considerably increased. It is necessary to develop analytical methods to analyse these compounds for quality control of formulations, quality control of diluted formulations before patient usage and understanding compatibility and stability. In this study, novel analytical methods were developed for mostly used anti cancer drugs, namely 5-fluorouracil (5- FU) and 5-azacytidine (5AC). Firstly, two analytical methodologies using capillary electrophoresis (CE) and liquid chromatography (LC) were developed for the determination of 5-FU and 5AC. The CE analysis was performed in a bare fused-silica capillary with 75 μm i.d. and total length of 50.0 cm with a buffer solution of 10.0 mM borate buffer, pH 11.5. The applied voltage was 20.0 kV. The LC analysis was performed with a YMC 30 column in reversed phase and a mobile phase of water–acetonitrile (90:10) at a flow rate of 0.8 mL/min. In both analyses, detection was by ultraviolet absorption. Also, molecularly imprinted polymers (MIPs) with different formulations (different functional monomers, porogens and monomer:crosslinker ratios) and morphologies (monolith and micro/nanosphericalbeads) were synthesized by using bulk and precipitation polymerization strategies. The adsorption capacity of imprinted polymers were compared to their corresponding non-imprinted polymer. MIP prepared by using bulk polymerization strategy with the formulation of 1:1:20 AA was chosen as selective solid phase extraction (SPE) sorbent due to its sorption capacity prior to determination of HPLC-DAD analysis. Selectivity of this imprinted polymer were examined by using 5-FU and 5AC molecules. To improve method, parameters were tested such as pH shaking time and amount of sorbent. So, optimization parameters of method were determined to be pH 5.0 of solution, 100.0 mg of sorbent, 10.0 mL 100.0 mg/L working solution, 60.0 min. sorption time.
  • Master Thesis
    Comparison Od Side Effects of Anti-Cancer Drugs in 2d and 3d And, Classical and Cell-On Cultures
    (Izmir Institute of Technology, 2016) Kankale, Deniz; Çağır, Ali; Pesen Okvur, Devrim; Pesen Okvur, Devrim; Çağır, Ali; 04.03. Department of Molecular Biology and Genetics; 04.01. Department of Chemistry; 04. Faculty of Science; 01. Izmir Institute of Technology
    The studies that aim to assess the effects of drugs developed against cancer at the cellular level use multiwell plates. However, these classical systems fail to reproduce the in-vivo like microenvironment necessary for realistic assessment. In addition, classical cell culture systems use high amount of materials increasing cost. On the other hand, lab-on-a-chip systems use minimal volumes of reagents and more importantly can mimic the in-vivo microenvironment via spatial and temporal control. Furthermore, it is known that cell response to drugs can be very different in 2D and 3D cell culture setups. Doxorubicin is a widely used anticancer drug. Here, doxorubicin uptake by highly metastatic human breast cancer cell line MDA-MB-231 and normal mammary epithelial cell line MCF10A were investigated using 2D and 3D, classical and cell-on-a-chip cultures. Drug uptake at 24, 48 and 72 hours various concentrations of the drug determined by measuring signal intensities from fluorescence microscopy images of cells. For cell viability assay, cells were stained with dapi and two cell lines were compared in systems. According to results, it was observed that 3D cell culture environment in chip provides more in-vivo like environment with less reagent consumption and cell viability is not correlated only with drug uptake.