Master Degree / Yüksek Lisans Tezleri
Permanent URI for this collectionhttps://hdl.handle.net/11147/3008
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Master Thesis Studies Toward the Synthesis of Novel Mdm2 Inhibitor Candidates(Izmir Institute of Technology, 2018) Dilek, Fikrican; Çağır, AliProtein 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 Investigation of Cytotoxic Properties of New Isoindol Derivatives in Lung and Cervical Cancers(Izmir Institute of Technology, 2019) Almusawi, Yasir; Şanlı Mohamed, GülşahCancer is one of the most common diseases in the world. Recently, there are many methods developed by researchers to treat this disease. One of these treatments is targeted for chemotherapy. It is preferred by researchers because it is less toxic and has fewer side effects than other cancer treatments. This study emphasizes the anticancer properties of the newly synthesized Isoindole derivatives. Thus, it was hoped to be a significant improvement based on new generation anticancer compounds with high efficacy and fewer side effects. The main objective of this study was to investigate the biological activity of seven newly synthesized Isoindole derivatives. The anticancer activity of these compounds was evaluated against HeLa (cervical carcinoma) and A549 (lung adenocarcinoma) cancer cell lines. This study is divided into three parts. Firstly, the cytotoxic activity of these compounds was determined by measuring the cell viability of each compound on HeLa and A549 cell lines. The main objective of this analysis is to measure the IC50 value of each compound and determine which compound is best to kill at least half of the cells. Secondly, the effects of programmed cell death and cell cycle were investigated for compounds with the best IC50 for each cell line by using Annexin V-FITC in flow cytometry. Finally, a scratch assay was performed to investigate the effect of these new Isoindole derivatives on cell migration.Master Thesis Development of Sub-Cellular Organelle Targeted Fluorescent Silica Nanoparticles(Izmir Institute of Technology, 2019) Yüksel, Almila; Özçelik, Serdar; Özçelik, SerdarSilica nanoparticles have been studied extensively in cellular applications due to their physicochemical properties. The surface of silica nanoparticles represent the key parameter in biological studies. Owing to their versatile surface chemistry, have ability to increase bioavailability and selectivity. Therefore, it is significant to understand how biomolecules interact with the surface of silica nanoparticles. The study reviews how synthesized both negative and positive potential silica nanoparticles and can transfer their properties to the cells. In the second part, our synthesized silica nanoparticles were characterized physicochemically using some instrumental devices. To answer the role of silica nanoparticles in the cells, some outcomes such as viability test, image analysis, colocalization analysis and mitochondrial membrane potential were investigated. A549 (adenocarcinomic human alveolar basal epithelial cells) and BEAS-2B (human bronchial epithelial cells) cell lines were selected in our studies. Our results showed the cytotoxicity was dose and time dependent in direct proportion. Mitochondrial accumulation were observed in cells treated with the silica nanoparticles according to Pearson’s Coefficient Correlation and Image J analysis. The study concluded that the silica nanoparticles can be used in the field of targeted delivery and bioimaging in cellular studies.Master Thesis Development of Mitochondria Targeted Gold Nanorods(Izmir Institute of Technology, 2019) Uçak, Hande; Özçelik, SerdarLung cancer has the largest number of lives for the global pattern of cancer death. However, the percentage of the cancer treatment is too low. Gold nanoparticles have a widely range in terms of biomedical applications in diagnosis, imaging because of their unique optical properties, simple synthesis techniques, biocompatibility and suitable for easy surface change. Redox reactions in the mitochondria generates a potential called as mitochondria membrane potential. The aim of the study is to design mitochondria targeted gold nanorods and to observe how the designed gold nanorods effects the mitochondria membrane potential by targeting the mitochondria on A549 and BEAS-2B cell lines. Gold nanorods were utilized by seed growth mediated method and the surface bioconjugation was performed with triphenyl phosphonium cation as a mitochondria targeted molecule. Poly (sodium-p-styrene sulfonate) was used to prevent aggregation during the bioconjugation process. Gold nanorods which had 30 nm x 10 nm in length and diameter depending on SEM images had well-defined absorption bands 513 nm and 774 nm in wavelength. Mito-pot analysis with the fluorescent intensity ratio and colocalization analysis with light intensity for targeting gold nanorods to mitochondria showed that the accumulation on mitochondria for TPP-GNR was higher than PSSGNR. TPP-GNR was more toxic than PSS-GNR for both of cell lines by investigations of MTT viability test. TPP-GNR targeted to mitochondria and it affected fundamental cellular functions in mitochondria. To concluded that accumulation on mitochondria was accomplished for TPP-GNR and the decreasing of mitochondria membrane potential was observed on this study.Master Thesis Desing and Synthesis of Bodipy Based Photosensitizers for Photodynamic Therapy(Izmir Institute of Technology, 2019) Dartar, Suay; Emrullahoğlu, Mustafa; Emrullahoğlu, MustafaPhotodynamic therapy is a promising modality for the non-invasive treatment of several cancerous and non-cancerous diseases. PDT is more preferable than other therapies due to its low damage to non-targeted tissues and its controllable characteristics. The therapy involves the activation of a photosensitizer under light illumination to generate singlet oxygen which is the cytotoxic agent employed against the cancerous tissues. Thus, there is currently a great effort to develop various photosensitizers. Among these, BODIPY based photosensitizers are distinguished due to certain characteristics, including excellent photostability, high extinction coefficients and high resistance to photobleaching. In this study, we aimed to synthesize and develop new BODIPY based photosensitizers for the use of photodynamic therapy agents. BODIPY skeleton was devised using the dibromoethylene unit from the 2,6-positions in order to enhance the π-conjugation system for red shift to longer wavelengths resulting in a deep penetration of tissue. Heavy atoms such as bromine were introduced to the BODIPY core to ensure the transition from singlet states to triplet states via intersystem crossing for the generation of singlet oxygen. Photophysical properties and spectroscopic measurements of photosensitizers were performed successfully. Finally the photodynamic activities of photosensitizers in cancerous cells were also investigated.Master Thesis The Development of Chemometric Methods Based on Molecular Spectroscopy for the Standardization of Production Processes and Product Traceability of Personal Care and Cleaning Products(Izmir Institute of Technology, 2019) Çiftçi İlmek, Berfu; Özdemir, DurmuşPersonal care and cleaning products are the main consumer goods. Changes in our heath caused by all of the chemicals that we exposed to everyday if these products are not produced according to the regulations and determined formulations. Because of this reason, quality control of the product formulation quantitatively is very important. There are some analytical methods for the determination of anion active matter, nonionic matter and total active matter in the product mixture. However, these techniques are expensive and do not give accurate results. The purpose of this thesis principally based on development of rapid, accurate and practical infrared spectroscopic technique based on multivariate chemometrics data analysis methods for the standardization of production processes and product traceability of personal care and cleaning products. In this thesis, two different products are studied which are namely liquid soap and shower gel. Fourier Transform Infrared spectroscopy coupled with Attenuated Total Reflectance accessory based chemometrics multivariate calibration models were developed for the quantitative determination of liquid soap and shower gel compounds. Genetic Inverse Least Squares was used as the chemometrics method for the development of multivariate calibration models in the quantitative determination of liquid soap and shower gel compositions. Standard error of cross validation and standard error of prediction values for content of the liquid soap samples were found 0.26% and 0.21 % (w/w %), respectively. Standard error of cross validation and standard error of prediction values for content of the shower gel samples were found 0.27 % and 0.30 % (w/w %), respectively.Master Thesis Hydrothermal Synthesis and Characterization of Tungsten Oxide Containing Organic-Inorganic Hybrid Material(Izmir Institute of Technology, 2019) Chilufya, Langson; Emirdağ Eanes, Mehtap; Eanes, MehtapImportance and a wide area of applications of solid-state oxides are well known. Metal oxides crystallize in wide variety but simple structures. Lately general opinion is that piezoelectric, ferromagnetic and catalytic properties of simple oxide structures will be improved if the metal oxides could have more complicated and detailed crystal structures. Therefore, research interest increased towards synthesizing complicated crystal structures. One of the methods to increase the complexity of the structure is the modification of inorganic oxides with organic ligands to synthesize complex hybrid materials. There are a great number of organic-inorganic hybrid materials with Keggin or Lindqvist Polyoxometalates structure containing Molybdenum and Tungsten. Usually Obtaining multifunctional hybrid materials, mostly requires grafting an organic functionalized group into the lacunary Keggin structures [XM11O39](n+4)-. Only Tungsten containing polyoxometalates can form a stable lacunary Keggin structures. A Lindqvist structures [M6O19]2- can also self-assemble with organic dyes to form a stable hybrid materials which have important applications. These polyoxotungstates, as an inorganic building blocks, were combined with organic compounds to obtain organic-inorganic hybrid materials. The carboxylic acid functionalized organotin grafted lacunary Keggin structure was coupled with different amines using N, N’-dicyclohexylcarbodiimide (DCC). Another hybrid material was formed by the association of the Lindqvist POM with phosphine based BODIPY derivative dye. The synthesized compounds were all characterized by SEM, FT-IR, TGA and Powder XRD. Since one of the organic moiety use was a BODIPY-type organic dye, the fluorescence properties of these newly synthesized compounds were investigated.Master Thesis Molecular Dynamics Simulation Study on the Interactions Between Dna and a Conjugated Polyelectrolyte (cationic Oligothiophene)(Izmir Institute of Technology, 2019) Nalıncı Bardak, Nehir; Elmacı Irmak, NuranThe absorption spectra of the cationic polythiophenes shift to the red, or the color changes in the solution are visible to the naked eye, when single-strand DNA (ssDNA) is added, so that they can be used as a tool for DNA detection, theranostic applications, and biological sensors. The red shift or color change is explained by the fact that the ssDNA leads to conformational changes in the polythiophene, but the form of structural change remains to be elusive (i.e. flattening, twisting, stacking, etc.). In this study, molecular dynamics (MD) simulations of complexes consisted by ssDNA sequences with different nucleotides and polythiophene containing cationic side group were performed to enlighten the experimental studies. For this purpose, force field parameters of polythiophene which are not present in the current databases, were generated. The interactions between them were analyzed to determine the nature of conformational changes in the polythiophene when ssDNA was added. MD simulations has been carried out with the CHARMM-compatible force field parameters obtained in the content of this work. Radius of gyration of oligomer increases with addition of ssDNA but is more affected by homopurine strand. Planarity index gets larger upon complexation with homopurine and T_rich strand, does not change with others. H-O and electrostatic interactions which are almost doubled in nonplanar complexes can be interpreted as the major sources of conformational changes in oligomer. Considering all types of interactions between atoms in duplexes, it was observed that planarity was high in structures with less interaction of oligomer side groups.Master Thesis Determination of Total Acid Number in the Optimization of Oleate Production by Using Fourier Transform Infrared Spectroscopy and Multivariate Calibration(Izmir Institute of Technology, 2019) Toygar Türkün, Nihan; Özdemir, DurmuşPolyethylene glycol oleate (PEG-Oleate) is a non-ionic surfactant, and is an important emulsifier for water-oil systems. It is produced by reacting oleic acid and polyethylene glycol (PEG) under vacuum for around 4 hours and at 160 °C, in the presence of acid catalyst which is para toluene sulfonic acid (PTSA). The quality and process control of this production is determination of total acid number (TAN) by the standard method ASTM D974 which is a color indicator titration. Although titration is a simple method, it is relatively time consuming and prone to human error. Besides, the solvents used in titration method, are significantly unhealthy for humans. The aim of this study is to develop fast and simple procedure for the determination of total acid number based on Fourier Transform Infrared Spectroscopy (FTIR) combined with multivariate calibration methods namely Genetic Inverse Least Squares (GILS) and Partial Least Squares (PLS). The reference total acid number of the samples collected during the esterification reaction, had been carried out by the ASTM D974 standart method and the Fourier Transform Infrared (FTIR) spectra of the same samples were also collected simultaneously with single reflection diamond Attenuated Total Reflectance (ATR) accessory. Univariate calibration was applied on a specific wavenumber corresponding to the ester peak around 1739 cm–1. Although the changes in the ester peak was showing an inrease associated to the esterification of the reactants, the results of the univariate calibration was unsucsesful. The best regression coefficient was found to be 0.997 by GILS method along with SECV and SEP as 2.295 and 2.694 mg KOH/g, respectively. The results of GILS showed that it is possible to monitor esterification process of PEG oleate.Master Thesis Mass Spectrometry-Based Proteome Analysis of Leishmania Major Parasite in Two Clinical Isolates Which Exhibit Different Impact on Virulence(Izmir Institute of Technology, 2018) Güvenç, Nazlı; Yalçın, TalatLeishmaniasis is a disease that covered under the title of neglected tropical diseases caused by protozoan parasites called Leishmania which can classify into three groups as visceral, cutaneous and mucocutaneous leishmaniasis. L. major is a type of parasite that causes cutaneous leishmaniasis and it is endemic in Iran, and Syria. However, cutaneous type leishmaniasis caused by L. major has been begun to detect in Turkey due to its close location to such countries. Moreover, the variety in the infectivity of L. major in a different region of Turkey has detected. Therefore, the uncertainty under the virulence effect of L. major is aimed to investigate. Large-scale protein analysis by mass spectrometry based proteomics has cleared up to proteome mapping for different organism recently. Generally, although two methodologies that involve gel-free and gel-based approaches have widely accepted for proteomic analysis, gel-free LC-MS/MS analysis were applied to characterize the proteome analysis of L. major parasite in two clinical case exhibiting passive and aggressive virulence effect on leishmaniasis. Finally, differential and common proteins that can affect the infectivity of L. major invastigated by shotgun analysis. As a result, samples showed that there are conflict results with the literature about GP63, secreted acid proteases, cysteine proteases and Peroxiredoxin proteins existence and also in the aggressive L. major cystathionine beta-synthase protein which has an role to synthesis of CPs and pyridoxal phosphate binding activity were proposed as a critical protein for L. major infectivity due to its association with SAPs, CPs.