Master Degree / Yüksek Lisans Tezleri

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

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Department: search.filters.department.Thesis (Master)--İzmir Institute of Technology, ChemistrySubject: search.filters.subject.Cancer cells

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Now showing 1 - 7 of 7
  • Master Thesis
    Synthesis of 1,5-Disubstituted 1,2,3-Triazole Modified Azacoumarins
    (01. Izmir Institute of Technology, 2022) Çağır, Ali; Çağır, Ali; 04.01. Department of Chemistry; 04. Faculty of Science; 01. Izmir Institute of Technology
    Cancer is a deadly disease that threatens human health and all life, and it is still a serious problem despite all scientific studies for more than half a century. Pharmacophores are a part of the structure of a drug (or drug candidate) responsible from the biological activity. This thesis is related with the synthesis of novel compounds having two well-known pharmacophore structures, 1,2,3-triazole and 1-azacoumarin. Both structures can be found in the structure of many biologically active molecules. Triazole modified coumarin derivatives are scarce in the literature. In this study, we aimed to improve the synthetic route toward the synthesis of 1- azacoumarin derivative modified by 1,2,3-triazole group at position 4-. Synthesis starts with the conversion of methyl 4-chloroanthranilate to the corresponding 4-OH azacoumarin. Then it is transferred into the 4-OTf group by simply addition of Tf group to OH under basic condition. After Sonogashira reaction and removal of TMS group 4- alkynyl-1-azacoumarin was produced. At this point, conversion of alkyne into 1,5- disubstituted 1,2,3-triazole was examined in the presence of Cp2Ni-Xantphos and RuCl(COD)Cp* catalytic systems but all of trials were failed probably due to the presence of ester group close to the reaction site. In further studies, design of the molecule will be reperformed and ester group will be moved over phenyl rings in order to test its biological activity over cancer cell lines.
  • Master Thesis
    Studies Toward the Asymmetric Synthesis of Ester Functionalized Novel 1,4-Oxazepine Derivatives
    (01. Izmir Institute of Technology, 2021) Bozoğlu, Hülya; Çağır, Ali; Çağır, Ali; 01. Izmir Institute of Technology; 04.01. Department of Chemistry; 04. Faculty of Science
    The MDM2/p53 is one of the most widely studied protein-protein interaction because of being a valuable target for the development of novel anticancer agents. MDM2 protein is the natural inhibitor of p53 protein which act as a tumor suppressor. When MDM2 is overexpressed, damaged DNA is allowed to replicate and therefore cancerous cells can be generated because p53 has lost of its activity. For this reason; maintaining the activity of wild-type p53 through inhibition of MDM2 can stop the proliferation of cancer cells. New drugs that inhibit this interaction are important for the treatment of cancer. The aim of the study is synthesize chiral 1,4-oxazepine-5-one 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 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. Up to this part of the synthesis, reactions were performed successfully. Then trityl group was removed by TFA and amino alcohol was obtained. Then addition of several α,β-unsaturated carbonyls to the deprotected amino alcohol was studied by coupling reagents such as HATU. Afterwards we performed some intramolecular cyclization attempts but all cyclization attempts were failed.
  • Master Thesis
    In-Vitro Evaluation Cytotoxic Potential of Novel Isoindole Derivatives on Various Cancer Cell Lines
    (01. Izmir Institute of Technology, 2021) Yemeztaşlıca Yetişkin, Egehan; Gülşah Şanlı Mohamed; 01. Izmir Institute of Technology
    Cancer, which is the disease of our age, arises because of a very complex set of mechanisms. Especially with the proliferation of cancer disease and the increase in cancer-related deaths, it has a great impact on the development of drug studies by improving existing treatments or researching new treatment methods. Cantharidine and its analogs are natural anhydrides with an inhibitory effect on protein phosphatases. However, they are not included in cancer therapies due to their toxicity. In recent studies, it has been found that derivatives of cantharidin as isoindole-1,3-dione and its derivatives have anticancer effects. The main purpose of this study to investigate the effects of four different drugs, which are newly synthesized isoindole derivatives for use in cancer treatment, on different cancer cells. The cytotoxic effects of drugs on A549 (human lung adenocarcinoma), HeLa (human cervical carcinoma), PC3 (human prostate carcinoma), MCF-7 (human breast carcinoma), and Caco-2 (human colorectal carcinoma) cell lines were investigated by the MTT assay method, and the optimum incubation time was determined, then IC50 values were calculated. Then, the IC50 concentrations of the drugs were applied at 48 hours, which is the optimum incubation period, and apoptotic stages and cell cycle stages were compared using flow cytometry to understand whether the drugs have a suppressive function in cancer development. Scratch assay was performed to investigate the migration effect of drugs on cells. The results showed that the drugs are suppressive to cancer cells and can be used for therapeutic purposes in the future.
  • Master Thesis
    Desing and Synthesis of Bodipy Based Photosensitizers for Photodynamic Therapy
    (Izmir Institute of Technology, 2019) Dartar, Suay; Emrullahoğlu, Mustafa; Dartar, Suay; Emrullahoğlu, Mustafa; Emrullahoğlu, Mustafa; 04.01. Department of Chemistry; 04.04. Department of Photonics; 04. Faculty of Science; 01. Izmir Institute of Technology
    Photodynamic 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
    Syntheses of Novel 4'-alkyl Substituted Klavuzon Derivatives
    (Izmir Institute of Technology, 2015) Kanbur, Tuğçe; Kanbur, Tuğçe; Çağır, Ali; Çağır, Ali; 04.01. Department of Chemistry; 01. Izmir Institute of Technology; 04. Faculty of Science
    Styryl lactones, which are compounds isolated from natural sources, are known for their cytotoxic property against variety cancer cell lines. Goniothalamin is a well known member of stryl lactones, include α,β-unsaturated δ-lactone in its structure. Being a α,β-unsaturated δ-lactone subunit is an important structural feature. Since, Goniothalamin has a selective cytotoxic property for cancer cell lines with no significant cytotoxic activity toward non-malignant cells. Recent studies show that naphthalen-1-yl substituted α,β-unsaturated δ-lactone derivative has slightly better cytotoxic activity than (R)-goniothalamin. As a result of that naphthalen-1-yl substituted α,β-unsaturated δ-lactones derivative was named as klavuzon by Çağır Research group. In this study it is aimed to synthesize 4’-alkyl substituted klavuzon derivatives. Syntheses were started with the Cu catalayzed addition of Grignard reagents to ethyl 4-(bromomethyl)-1-naphthoate to achieve alkyl substitution. For lactone synthesis a well-known three steps synthesis was used starting from aldehyde. Thus 1-naphthoate esters first reduced to alcohol then oxidized to aldehyde by using LiAlH4 and PCC. These aldehydes were reacted with allymagnesium bromide then formed alcohols were acrylated with acryloyl chloride to yield the corresponding esters. Finally, target molecules were synthesised by ring closing metathesis by using 2nd generation Grubbs’ catalyst.
  • Master Thesis
    Immobilization of Olive Leaf Extract on Chitosan Nanoparticles and Investigation of Their Effects on Cancer Cell Lines
    (Izmir Institute of Technology, 2014) Özdamar, Burcu; Şanlı Mohamed, Gülşah; Şanlı Mohamed, Gülşah; 04.01. Department of Chemistry; 04. Faculty of Science; 01. Izmir Institute of Technology
    Cancer incidence and mortality rates are increasing worldwide in both economically developed and developing countries. Breast cancer in females and lung cancer in males are the most common cancer types. Epidemiological research has provided increasing evidence that dietary habits, especially Mediterranean diet which has high consumption of olive oil and its products, may play an important role in lung and breast cancer. Due to their preventive effect against cancer, olive leaf extract rich in polyphenols was immobilizied on chitosan nanoparticles which are good drug carriers because of their biocompatible and biodegradable properties with the help of capability of passing through biological barriers. For this aim, olive leaf extract loaded chitosan nanaoparticles were synthesized by ionotropic gelation mechanism. Optimum conditions to synthesize nanoparticles were determined by investigation of the effect of chitosan and tripolyphosphate mass ratio, initial pH of chitosan solution, concentration of olive leaf extract and incubation time of olive leaf extract and tripolyphosphate with chitosan solution. Characterization of nanoparticles was performed by dynamic light scattering, atomic force microscopy and infrared spectroscopy. To investigate the anticancer properties of nanoparticles, molecular biological studies were performed by in vitro cytotoxicity studies based on MTT assay, in vitro cell cycle analysis and apoptosis by flow cytometer and imaging of cells by optical microscopy. In results, olive leaf extract loaded chitosan nanaoparticles obtained approximately 91.25 nm and showed more cytotoxicity than chitosan nanoparticles, chitosan and olive leaf extract for both lung and breast cancer cells. In contrast, there was no cytotoxicity for healthy cells. These effects were supported by cell cycle analysis. Also in optical imaging, lower number of cells and morfological differences on cancerous cells which supports the cytotoxicity results were observed. We can conclude that our results will open a new approach to use not only cytotoxic anticancer drug for cancerous cells but also biocompatible material for biomedical applications.
  • Master Thesis
    The Effect of Doxorubicin-Albumin Magnetic Nanoparticles on Prostate and Lung Cancer Cells
    (Izmir Institute of Technology, 2012) Zeybek, Ayça; Şanlı Mohamed, Gülşah; Şanlı Mohamed, Gülşah; 04.01. Department of Chemistry; 04. Faculty of Science; 01. Izmir Institute of Technology
    Chemotherapy is a major therapeutic approach for treatment of a wide range of cancers. But unfortunately, this therapeutic approach has got a lot of side effects on healthy tissues as well as cancerous cells. Although doxorubicin is one of the most potent and widely used anticancer drugs, it has some side effects on healthy tissues, as well. Therefore, most researchers have studied various doxorubicin carrier systems for targeted delivery. For this purpose, doxorubicin loaded magnetic albumin nanospheres (M-DOX-BSA-NPs) were synthesized. The main objective of this project was basically to determine the cytotoxic, apoptotic and cell cycle effects of BSA-NPs, M-BSA-NPs, DOX, BSA-DOX-NPs and M-DOX-BSA-NPs against prostate and lung cancer cells and compare them. Beside this, it is aimed to understand how cells look like before and after giving doxorubicin and M-DOX-BSA-NPs by using optical microscopy and compare them. Another objective of this project was to determine where M-DOX-BSA-NPs reach out into the cell by using concofal microscopy; and to explore proteins’ differentiations between control groups and lung and prostate cancer cells in which DOX and M-DOX-BSA-NPs were applied, by proteomic studies. In this study, the experimental results which were also supported by literature findings, demonstrated that M-DOX-BSA-NPs were more toxic than free doxorubicin, and this complex was more effective for prostate cancer cells than lung cancer cells. As a result of this study, it was determined that this complex was synthesized as a target chemotherapy drug delivery system. Accordingly, this complex may affect to other cancer types, and it can be carried out by new drug designers and treatments.