Master Degree / Yüksek Lisans Tezleri
Permanent URI for this collectionhttps://hdl.handle.net/11147/3008
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Master Thesis Naphthoquinones From Natural Sources and Their Bioactivities(Izmir Institute of Technology, 2019) Kul, Demet; Bedir, ErdalOnosma L. is a large heterogenic genus of Boraginaceae family includes about 230 species distributed mainly in Central Asia and the Mediterranean region. According to ‘Flora of Turkey, Onosma genus is represented with 104 species and 108 taxa and 52% of which are endemic. Phytochemical studies have revealed that Onosma species possess various constituents including alkaloids, naphthoquinones, polyphenols, phytosterols, terpenoids and fatty acids. Naphthoquinones are naturally widespread secondary metabolites deriving from some higher plants, fungi and bacteria, and have shown significant biological activities such as cytotoxic, antibacterial, antifungal and wound healing. In this thesis, bioassay-guided isolation studies were performed on Onosma aksoyii and Onosma isaurica to obtain naphthoquinone type cytotoxic compounds and investigate their topoisomerase inhibitory properties. Isolation studies were guided by MTT assay using three human cancer cell lines (HeLa, HCC-1937, DU-145) and a nontumor cell line (MRC-5). whereas the enzyme inhibition tests were against human topoisomerases IIα and IIβ. Six compounds, one of which was new (OA-PE-D1), were isolated using chromatographic methods and their structures were elucidated by spectral methods (1D, 2D NMR, and MS). The known compounds were acetylshikonin, β,β- dimethylacrylshikonin, arnebidin, arnebifuranone and shikonofuran E. The cytotoxicity screenings showed that these compounds had IC50 values ranging from 6.485 μM to 32 μM. According to topoisomerase inhibition studies, OA-PE-D1 and β,β- dimethylacrylshikonin showed promising inhibitory effects on topoisomerase IIβ at dose of 1 mg/mL.Master Thesis The Effects of Naphthoquinones Isolated From Onosma Species on Dna Topoisomerases and Their Cytotoxic Properties(Izmir Institute of Technology, 2018) Güzel, Özge; Bedir, Erdal; Bedir, Erdal; Zencir, SevilOnosma L. genus (Boraginaceae) comprises of 230 species that is represented by 102 species and 108 taxa in the flora of Turkey. As 50% of the genus is endemic, Anatolia can be considered as the gene center of Onosma species. Phytochemical investigations performed on Onosma genus have led to the identification of various naphtoquinones, alkaloids and phenolic constituents. Biological activity studies on naphthoquinones demonstrated antimicrobial and wound-healing properties as well as cytotoxicity. In this thesis, Onosma taurica var. taurica and O. mollis were taken into cytotoxic activity-guided isolation studies, by MTT using seven human cancer cell lines (DU145, Capan-1, HCC-1937, MCF-7, HeLa, HEPG2, A-459) and a normal cell line (MRC-5), to isolate their bioactive compounds. Additionally, the isolation studies were guided by enzyme inhibition tests towards human Topoisomerases I and II. Six compounds were isolated using chromatographic methods, and the structures of the five of them were elucidated by spectral methods, (1D-, 2D NMR and HR-ESI-MS) as acetylshikonin, shikonin, β-hydroxyisovalerylshikonin, β,β-dimethylacrylshikonin and deoxyshikonin. The isolated compounds showed prominent cytotoxicity with IC50 values ranging from 1.83 to 25 M. β,β-dimethylacrylshikonin was found to be the most cytotoxic compound (IC50: 1.84 μM versus HCC-1937), whereas β-hydroxyisovalerylshikonin on Topoisomerase I and II (each at 25 M dose) exhibited strong inhibitory effects.