Investigation of the effect of 4'-alkylıklavuzon derivatives on nucleotide synthesis and nucleocytoplasmic transport için kapak resmi
Investigation of the effect of 4'-alkylıklavuzon derivatives on nucleotide synthesis and nucleocytoplasmic transport
Başlık:
Investigation of the effect of 4'-alkylıklavuzon derivatives on nucleotide synthesis and nucleocytoplasmic transport
Yazar:
Kutluer, Meltem, author.
Yazar Ek Girişi:
Fiziksel Tanımlama:
xi, 45 leaves:+ 1 computer laser optical disc.
Özet:
In anti-cancer agent development studies one of the most significant issue is to get an agent that specifically targets cancer cells without any effects on healthy cells. Goniothalamin, that is a styryl lactone isolated from Goniothalamus plant species, is an anti-cancer agent that has selective anti-proliferative activity on cancer cell lines. Klavuzon and derivatives, which can be thought as analogs of goniothalamin, are more cytotoxic in cancer cells compared to goniothalamin. Previous structure activity relationship studies implies that α,β-unsaturated δ-lactone moiety is the source of the biological activity. Since it behaves as Michael acceptor, in this thesis possible irreversible inhibitions of two separate intracellular targets are investigated. In the first part, thymineless death caused by possible thymidylate synthase inhibition has been studied. Anti-proliferative effect of 4’-methylklavuzon in HuH-7 cancer cell line was tested by using MTT. Viability of klavuzon treated cells did not changed significantly in the absence and presence of varying concentration of additional thymidine supplement, and it is concluded that thymineless death is not a crucial mechanism for klavuzon derivatives. In the second part, 4’-methylklavuzon and its derivatives were tested on HeLa cell line to investigate inhibitory effect on the nucleocytoplasmic transport. Immunocytochemistry was used to demonstrate nucleocytoplasmic localization of Riok2 protein which is transferred from nuclei to cytoplasm by CRM1 nuclear export protein. Successfully, all tested klavuzon derivatives inhibit CRM1 nuclear export protein. Potency of the inhibition depends on the size of the alkyl substituent at 4’- position of klavuzon.
Yazar Ek Girişi:
Tek Biçim Eser Adı:
Thesis (Master)--İzmir Institute of Technology: Biotechnology and Bioengineering.

İzmir Institute of Technology: Biotechnology and Bioengineering--Thesis(Master).
Elektronik Erişim:
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