Master Degree / Yüksek Lisans Tezleri

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

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Now showing 1 - 3 of 3
  • 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
    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
    Studies Toward the Asymmetric Synthesis of Novel Chiral 1,4-Oxazepan Derivatives
    (01. Izmir Institute of Technology, 2020) Vural, Ezgi; Çağır, Ali; Çağır, Ali; 01. Izmir Institute of Technology; 04.01. Department of Chemistry; 04. Faculty of Science
    Pharmacophore design to inhibit the interaction between p53 and MDM2 became a novel approach for cancer therapy. p53, known as the guardian of genome, controls the cell cycle arrest, apoptosis and DNA repair under stress. Nonetheless, when over-expressed, MDM2 causes proliferation in the cell and eventually tumorgenesis. The feedback mechanism between p53 and MDM2 arises from the interaction of p53 through the hydrophobic cleft which consists of Phe19, Trp23 and Leu26 aminoacids in the N-terminal of MDM2. In this study, it was aimed to synthesize a new, chiral 1,4-oxazepan-5-one derivatives by asymmetric synthesis. (R)-2-amino-2-(4-chlorophenyl)acetic acid was used as starting material. Amino group was protected by trityl group then the carboxylic acid part was reduced by LiAlH4 to produce N-trityl-protected amino alcohol. Dess Martin periodinane was used for the oxidation of the alcohol to the aldehyde, then 3-chlorophenylmagnesium bromide was added to the aldehyde by Grignard reaction. Deprotection of N-trityl was performed with TFA then, coupling reactions of produced aminoalcohol with different α,β-unsaturated carboxylic acids were performed by HATU and DIPEA. Despite all of the attempts, cyclization to seven membered 1,4-oxazepan-5-one ring was never achieved.