Master Degree / Yüksek Lisans Tezleri
Permanent URI for this collectionhttps://hdl.handle.net/11147/3008
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Master Thesis Studies Toward the Asymmetric Synthesis of Ester Functionalized Novel 1,4-Oxazepine Derivatives(01. Izmir Institute of Technology, 2021) Bozoğlu, Hülya; Çağır, AliThe 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 Investigation of Anticancer Properties of the Novel Synthesixed Pyrrole Derivatives as Potential Tyrosine Kinase Inhibitors(Izmir Institute of Technology, 2017) Kaya, Meltem; Şanlı Mohamed, GülşahIn cancer treatment, chemotherapy has some serious side effects, because it targets active cells which might not be cancer cells. Mouth, hair, nail, bone marrow cells are some examples of active cells. For the reason that chemotherapy has side effects, targeted therapy become more important. Tyrosine kinases are most interested target, because they are necessary for cell growth and metastasis. Active form of tyrosine kinases can cause tumour growth and proliferation, angiogenesis, metastasis and antiapoptotic effects. Based on these vital role of tyrosine kinases, they became more important target in cancer treatment. Pyrrole derivatives have been used chemotherapy drugs for years. Semaxanib and Sunitinib, indole derivatives, are tyrosine kinase inhibitors. The main purpose of this research is to investigate the biologic activities of novel synthesized seven pyrrole derivatives, their activities on migration, apoptosis, cell cycle, and mTOR downstream as a potential tyrosine kinase inhibitor. The results of this research proved that these seven compounds have toxicity on HeLa cells with the IC50 values of 140.60 μM, 382.82 μM, 366.44 μM, 542.00 μM, 255.86 μM, 148.59 μM, 171.40 μM, respectively, but toxicity effects of drugs do not depend on apoptosis mechanism. Beside this, D1 and D3 were able to effect cell cycle by arresting at S phase for D1 and G1 phase for D3. It was demonstrated that D1 and D3 inhibited cell migration. And this inhibition was reported as in a relation with overexpression of p- 4EBP1, inhibition of p-p70S6K (Thr) and p-p70S6K (Shr) proteins. Considering all results, D1 and D3 might be potent inhibitory of metastasis of HeLa cells with respect to its effect on cell cycle, migration, p-4EBP1, p-p70S6K (Ser), and p-p70S6K (Thr) protein levels.