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SÜZGÜN, PELİN

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PELİN

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2015 - 20192
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    Recent Advances in Apoptosis: The Role of Hydrazones
    (BENTHAM SCIENCE PUBL LTD, 2019) SÜZGÜN, PELİN; Cikla-Suzgun, Pelin; Kucukguzel, S. Guniz
    The process of programmed cell death in higher eukaryotes (apoptosis), is generally characterized by distinct morphological characteristics and energy-dependent biochemical mechanisms. Apoptosis is considered as a vital component of various processes including normal cell turnover, proper development and functioning of the immune system, hormone-dependent atrophy, embryonic development and chemical-induced cell death. Apoptosis seems to play an important key role in the progression of several human diseases like Alzheimer's disease, Parkinson's disease and many types of cancer. Promotion of apoptosis may be a good approach for the prevention of cancer cell proliferation. In early studies, antitumor compounds have been found to induce the apoptotic process in tumor cells. On the other hand, several hydrazones were reported to have lower toxicity than hydrazides due to the blockage of -NH2 group. Therefore, the design of hydrazones that activate and promote apoptosis is an attractive strategy for the discovery and development of potential anticancer agents. The aim of this review is to provide a general overview of current knowledge and the connection between apoptosis and hydrazone. It is also the guide for the apoptotic activities of new hydrazone derivatives.
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    Synthesis of Tolmetin Hydrazide-Hydrazones and Discovery of a Potent Apoptosis Inducer in Colon Cancer Cells
    (WILEY-V C H VERLAG GMBH, 2015) ÖZSAVCI, DERYA; Kucukguzel, S. Guniz; Koc, Derya; Cikla-Suzgun, Pelin; Ozsavci, Derya; Bingol-Ozakpinar, Ozlem; Mega-Tiber, Pinar; Orun, Oya; Erzincan, Pinar; Sag-Erdem, Safiye; Sahin, Fikrettin
    Tolmetin hydrazide and a novel series of tolmetin hydrazide-hydrazones 4a-l were synthesized in this study. The structures of the new compounds were determined by spectral (FT-IR, H-1 NMR) methods. N-[(2,6-Dichlorophenyl)methylidene]-2-[1-methyl-5-(4-methylbenzoyl)-1H-pyrrol-2-yl]acetohydrazide (4g) was evaluated in vitro using the MTT colorimetric method against the colon cancer cell lines HCT-116 (ATCC, CCL-247) and HT-29 (ATCC, HTB-38) to determine growth inhibition and cell viability at different doses. Compound 4g exhibited anti-cancer activity with an IC50 value of 76M against colon cancer line HT-29 (ATCC, HTB-38) and did not display cytotoxicity toward control NIH3T3 mouse embryonic fibroblast cells compared to tolmetin. In addition, this compound was evaluated for caspase-3, caspase-8, caspase-9, and annexin-V activation in the apoptotic pathway, which plays a key role in the treatment of cancer. We demonstrated that the anti-cancer activity of this compound was due to the activation of caspase-8 and caspase-9 involved in the apoptotic pathway. In addition, in this study, we investigated the catalytical effect of COX on the HT-29 cancer line, the apoptotic mechanism, and the moleculer binding of tolmetin and compound 4g on the COX enzyme active site.