Master Degree / Yüksek Lisans Tezleri
Permanent URI for this collectionhttps://hdl.handle.net/11147/3008
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Master Thesis Secondary Metabolites From Marine Derived Actinobacteria and Their Bioactivities(01. Izmir Institute of Technology, 2024) Can, Özge; Bedir, Erdal; Can, Özge; Bedir, Erdal; 03.01. Department of Bioengineering; 03. Faculty of Engineering; 01. Izmir Institute of TechnologyAktinobakteriler, antibakteriyel ve antikanser bileşikler dahil olmak üzere birçok biyoaktif ikincil metabolit üretebilmesi açısından dikkat çekmektedir. Bu tez kapsamında, İzmir (Türkiye) Ilıca Körfezi'nden Aktinobakteri olduğu öngörülen bakteriler izole edilerek antimikrobiyal potansiyelleri ortaya konmuştur. On iki izolatın fermantasyon sıvıları etil asetat ile ekstre edilerek, disk difüzyon testi ile seçilen patojenlere karşı (Staphylococcus aureus, Escherichia coli ve Candida albicans) taranmıştır. İzolatların çoğunluğu en az bir patojene karşı antimikrobiyal aktivite göstermiştir. Elde edilen izolatların morfolojik özelliklerine dayanarak Streptomyces üyeleri oldukları düşünülmüştür. Antimikrobiyal potansiyel ve ikincil metabolit profillerine dayanarak, 35M1 izolatı ileri çalışmalar için seçilmiştir. İlgili izolatın tüm genom dizilim (WGS) analizi sonucu türü Streptomyces sp. 35M1 olarak netleştirilmiş ve DDBJ/ENA/GenBank sistemine kaydedilmiştir (Erişim numarası: JBCLWP010000000). Preparatif ölçekli fermantasyonu takiben biyoaktivite rehberli izolasyon çalışmaları gerçekleştirilmiş, beş bileşik saflaştırılarak karakterize edilmiştir. Bu bileşikler; Actinomycin D (ActD), Actinomycin X2 (ActX2), Actinomycin XOβ (ActXOβ), Collismycin A (ColA) ve Collismycin C (ColC) olarak tanımlanmıştır. Sonrasında, ilgili moleküllerin antibiyofilm etkileri araştırılmış ve ActD ile ActX2'nin Metisiline dirençli Staphylococcus aureus, Listeria monocytogenes ve Staphylococcus epidermidis 'e karşı biyofilm inhibitör etkileri olduğu ortaya konmuştur. Son olarak, yeterli miktarda bulunan bileşikler ile (ActD, ActX2 ve ActXOβ) bir sinerjizm çalışması yapılmıştır. ActD ile Nalidiksik asit ve ActX2 ile Ampisilin, Nalidiksik asit ve Rifampisin kombinasyonları, gram-negatif E. coli 'ye karşı sinerjik etki göstermiş ve bu durum literatürde ilk kez rapor edilmiştir.Master Thesis Development of Microfluidic Devices for Investigating Small Molecule Induced Chemotaxis of Dendritic Cells(01. Izmir Institute of Technology, 2023) Tekin, Hüseyin Cumhur; Bedir, Erdal; Bedir, Erdal; Tekin, Hüseyin Cumhur; 03.01. Department of Bioengineering; 03. Faculty of Engineering; 01. Izmir Institute of TechnologyMicrofluidics is the core branch of science and technology in which interdisciplinary research is conducted with a low amount of samples in microchannels ranging from 10-100 μm. The main objective of this thesis is to design and fabricate a chemotaxis microfluidic device (CMD) from the poly-methyl methacrylate (PMMA) substrate to analyze the immune cell behavior against cancer cells. The patterns of the three-layered CMD were generated using laser ablation. During the fabrication, Power (P) and Speed (S) values were varied to determine the optimal P-S combination. Then, the structural properties of microfluidic channels in the CMD were examined via microscope. The mechanical properties and liquid handling abilities of CMDs were also investigated through tensile and leakage tests, respectively. Moreover, cell viability of DC2.4 dendritic cells (DCs) and B16-F10 murine melanoma (B16-F10) cells in CMDs sterilized through either autoclaving or UV treatment were determined to test the suitability of CMDs via Live/Dead Assay. The highest cell viability for DCs and B16-F10 was obtained in autoclaved CMDs. For the maturation of DCs before seeding into CMD, DCs were stimulated with lipopolysaccharide (LPS) and Astragaloside VII (AST-VII) at various concentrations. While the cytotoxicity of LPS and AST-VII were determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, the expression levels of specific chemokine receptors were also analyzed through flow cytometry. Lastly, stimulated DCs and B16-F10 were simultaneously cultured in the CMD, and the migratory behavior of DCs against B16-F10 was time-dependently studied. Consequently, CMD that provided cost-effective and rapid analysis of intercellular interactions was successfully developed.Master Thesis Investigation on the Bioactive Secondary Metabolites of the Endophytic Fungus Penicillium Roseopurpureum(01. Izmir Institute of Technology, 2022) Dizmen, Berivan; Bedir, Erdal; Bedir, Erdal; 01. Izmir Institute of Technology; 03.01. Department of Bioengineering; 03. Faculty of EngineeringIn recent years, endophytic fungi have been considered as significant resources of new bioactive secondary metabolites, so they are predicted to have an important impact in drug discovery and development. In our preliminary study, the chemical diversity and cytotoxic activity of an endophytic fungus, namely Penicilium roseopurpureum 1E4BS1 isolated from Astragalus angustifolius, have been demonstrated. Based on these data, it was aimed to obtain bioactive secondary metabolites of P. roseopurpureum 1E4BS1 within the scope of this thesis. Firstly, a fermentation study was carried out in a rotary shaker at 180 rpm, 25 ºC for 20 days, and the obtained broth was extracted with EtOAc. Secondly, nine metabolites were isolated from the EtOAc extract by chromatographic methods, and the structures of compounds were elucidated by spectral methods (1D-, 2D NMR, and MS). The structure elucidation studies revealed that seven metabolites had anthraquinone backbone, whereas two compounds were found to be derivatives of curvularin from macrolide group. A chemical structure search confirmed that five of the metabolites were new for nature. Cytotoxic activity of the compounds and the EtOAc extract was tested against three cancer (DU145, LnCaP, and PC3) and normal (RPWE-1) cell lines by MTT cell viability assay. The metabolite PR-EB-01 exhibited the highest activity with IC50 values of 26.0, 37.2, 24.7, and 30.9 μM against LNCaP, PC3, DU145, and RPWE-1 cells, respectively.Master Thesis Phytochemical Studies on the Mastic Gum of Pistacia Lentiscus Var. Chia Collected From Karaburun Peninsula and Bioactivities of Isolates(01. Izmir Institute of Technology, 2021) Bedir, Erdal; Bedir, Erdal; Ballar Kırmızıbayrak, Petek; 03.01. Department of Bioengineering; 03. Faculty of Engineering; 01. Izmir Institute of TechnologyPistacia lentiscus L. is an evergreen shrub or tree-like plant named as 'mastic tree'. The phytochemical studies of Chios mastic gum have revealed that it is a complex natural product comprising several organic ingredients like natural polymers, essential oils and triterpenic compounds. Triterpenes are the main components of mastic gum, and they are thought to be responsible for important biological activities such as anti-cancer, anti-ulcer, cytotoxic, antidiabetic, and anti-inflammatory. Within the scope of this thesis, mastic gum collected from the mastic trees (Pistacia lentiscus var. chia) grown on the Karaburun peninsula of İzmir was investigated to reveal its phytochemical composition and neuroprotective effects of the isolates. Isolation and purification studies utilizing chromatographic methods are followed by structural elucidation of the isolates by spectroscopic methods (1D NMR, 2D NMR, MS and X-RAY). Detailed analysis of the obtained spectra helped us to establish structures of 14 molecules possessing triterpenic skeleton, and two of them turned out to be undescribed compounds. The bioactivity of selected compounds was screened for their neuroprotective effects against H2O2 induced oxidative stress on differentiated and undifferentiated SH-SY5Y cells. Two compounds showed neuroprotective effects against H2O2-induced cell death on undifferentiated SH-SY5Y cells at 5 and 10 µM concentrations, while the other compounds either showed little or no effect. This study provides promising new insights into the use of mastic gum or its components in the treatment of neurodegenerative diseases.Master Thesis Docking Studies on Selected Sapogenins Targeting Androgen and Estrogen Receptors(01. Izmir Institute of Technology, 2021) Bedir, Erdal; Çömlekçi, Yiğit Ege; Bedir, Erdal; 01. Izmir Institute of Technology; 03.01. Department of Bioengineering; 03. Faculty of EngineeringNatural products have been used in the treatment of various diseases in history, and they are still in use today. Sapogenins are natural products derived from plant and animal sources that also have numerous biological activities. Furthermore, some sapogenins have been found to be active in common cancers such as prostate and estrogen alpha-mediated breast cancer and exert their effects via the androgen and estrogen receptors. For this reason, identifying alternative ligands for these receptors may aid in enhancing the benefits or avoiding adverse effects. Traditional or advanced molecular screening techniques are available with their respective applications. However, these applications have some limitations, such as being complicated and costly or requiring a significant amount of time due to the large number of molecules involved. With advancements in technology, in-silico methods such as molecular docking have developed into a highly accurate and cost-effective method for high throughput screening. Additionally, rapid and high-quality in-silico visualization of docked ligands and their interactions serves as a preliminary step toward determining structure-activity relationships. The molecular docking method was used in this study to identify novel androgen and estrogen receptor ligands, and to evaluate the structure-activity relationship of sapogenin molecules, which were selected from our research group's molecule library. Moreover, the Swiss Target Prediction web service was used to determine the probability of bindings prior to molecular docking. The molecular docking results demonstrated that nine of the selected sapogenins were more bindable to the androgen receptor than testosterone, whereas another nine were found to be more bindable to the estrogen receptor than estradiol. Additionally, immunoblotting was utilized to validate the activity of several molecules by examining their effects on PSA levels for androgen receptor binding.