Yazar "Emirdag, Safiye" seçeneğine göre listele

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    Design, semi-synthesis and examination of new gypsogenin derivatives against leukemia via Abl tyrosine kinase inhibition and apoptosis induction
    (Elsevier, 2022) Ulusoy, Nafia Gokce; Emirdag, Safiye; Sozer, Ece; Radwan, Mohamed O.; Ciftci, Halilibrahim; Aksel, Mehran; Ozmen, Ali
    Chronic myelogenous leukemia (CML) is characterized by Philadelphia translocation arising from Bcr-Abl fusion gene, which encodes abnormal oncoprotein showing tyrosine kinase (TK) function. Certain mutations in kinase domain, off-target effects and resistance problems of current TK inhibitors require the discovery of novel Abl TK inhibitors. For this purpose, herein, we synthesized new gypsogenin derivatives (6a-l) and evaluated their anticancer effects towards CML cells along with healthy cell line and different leukemic cells. Among these compounds, compound 6l was found as the most active anti-leukemic agent against K562 CML cells compared to imatinib exerting less cytotoxicity towards PBMCs (healthy). This compound also revealed significant anti -leukemic effects against Jurkat cell line. Besides, compound 6l enhanced apoptosis in CML cells with 52.4 % when compared with imatinib (61.8 %) and inhibited Abl TK significantly with an IC50 value of 13.04 +/- 2.48 mu M in a large panel of kinases accentuating Abl TK-mediated apoptosis of compound 6l in CML cells. Molecular docking outcomes showed that compound 6l formed mainly crucial interactions in the ATP-binding cleft of Abl TK similar to that of imatinib. Ultimately, in silico pharmacokinetic evaluation of compound 6l indicated that this compound was endowed with anti-leukemic drug candidate features.
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    Design, Synthesis and Biological Evaluation of Novel Gypsogenin Derivatives as Potential Anticancer and Antimicrobial Agents
    (Wiley-V C H Verlag Gmbh, 2024) Emirdag, Safiye; Ulusoy, Nafia Gokce; Aksel, Mehran
    Natural compounds are important sources for the treatment of chronic disorders such as cancer and microbial infectious disorders. In this research, Gypsogenin and its derivatives (2 a-2 f) have been tested against different cancer cell lines (MCF-7, HeLa, Jurkat and K562 cell lines) and further analyzed for cell proliferation, cell death type, and for act of the mechanism. Cell proliferation was determined by the MTT method and cell death types were analyzed with HO/PI staining. Fibroblast Growth Factor 1 (FGF-1), Interleukin 1 (IL-1), Interleukin 6 (IL-6), and Tumor Necrosis Factor Alpha (TNF-alpha), key players in breast cancer development and progression, were determined by Elisa kits. Results showed that compound 2 e inhibited the MCF-7 cell line proliferation with an IC50 value of 0.66 +/- 0.17 mu M with 93.38 % apoptosis rate. Compound 2 e also decreased FGF-1, IL-1, IL-6, and TNF-alpha levels. Molecular docking studies performed in the binding site of FGFR-1 indicated that compound 2 e formed key hydrogen bonding with Arg627 and Asn568. Besides, compounds 2 a-2 f were evaluated for their antimicrobial activities against gram-negative and gram-positive bacteria and C. albicans via the microdilution method. Overall, compound 2 e stands out as a potential anticancer agent for future studies. image
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    EGFR-Targeted Pentacyclic Triterpene Analogues for Glioma Therapy
    (Mdpi, 2021) Ciftci, Halil I.; Radwan, Mohamed O.; Sever, Belgin; Hamdy, Ahmed K.; Emirdag, Safiye; Ulusoy, N. Gokce; Sozer, Ece
    Glioma, particularly its most malignant form, glioblastoma multiforme (GBM), is the most common and aggressive malignant central nervous system tumor. The drawbacks of the current chemotherapy for GBM have aroused curiosity in the search for targeted therapies. Aberrantly overexpressed epidermal growth factor receptor (EGFR) in GBM results in poor prognosis, low survival rates, poor responses to therapy and recurrence, and therefore EGFR-targeted therapy stands out as a promising approach for the treatment of gliomas. In this context, a series of pentacyclic triterpene analogues were subjected to in vitro and in silico assays, which were conducted to assess their potency as EGFR-targeted anti-glioma agents. In particular, compound 10 was the most potent anti-glioma agent with an IC50 value of 5.82 mu M towards U251 human glioblastoma cells. Taking into account its low cytotoxicity to peripheral blood mononuclear cells (PBMCs), compound 10 exerts selective antitumor action towards Jurkat human leukemic T-cells. This compound also induced apoptosis and inhibited EGFR with an IC50 value of 9.43 mu M compared to erlotinib (IC50 = 0.06 mu M). Based on in vitro and in silico data, compound 10 stands out as a potential orally bioavailable EGFR-targeted anti-glioma agent endowed with the ability to cross the blood-brain barrier (BBB).
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    A new hybrid ligand and its metal complexes from a natural plant (Styrax officinalis) bearing egonol, thiosemicarbazone and oxime units, and their anti-cancer activities
    (Wiley, 2022) Babahan-Bircan, Ilknur; Emirdag, Safiye; Ozmen, Ali; Abbak, Muruvvet; Ujam, Oguejiofo T.; Demirkaya, Ilke; Gunay, M. Emin
    A novel hybrid ligand, a vic-dioxime ligand (ETO), containing thiosemicarbazone and egonol moieties from a natural plant (Styrax officinalis) and its trinuclear [Ni(II), Cu(II), Co(II), and Fe(II)] and mononuclear [Pd(II) and Zn(II)] complexes have been synthesized and characterized. The ligand, complexes, and natural components were characterized by conventional spectroscopic techniques (IR, NMR, and MS) and evaluated against two human cancer cell lines (MCF-7 and PC-3) to determine their antiproliferative and apoptotic properties. Apoptotic or necrotic effects were detected in both cancer cell lines using the Hoechst/propidium iodide double-staining method. Paclitaxel was used as a positive control (1 mu M). The results displayed that the compounds obtained in this study were effective in the concentration range of 5-40 mu M in prostate and breast cancer cell lines. It can be said that the compounds (egonol, its derivatives, hybrid ligand, and its metal complexes) are mostly more effective in PC-3 migration lines. Consequently, the cytotoxic efficiencies of [Cu-3(ETO)(2)center dot 4Cl], 5.27 mu M for MCF-7 and 13.44 mu M for PC-3 and [Zn (ETO)center dot 2Cl] 11.73 mu M for MCF-7 and 9.32 mu M for PC-3 were observed to be close to paclitaxel (a drug used as a cancer chemotherapeutic agent). [Cu-3(ETO)(2)center dot 4Cl] were more effective on the MCF-7 cell line. Besides this result, [Zn (ETO)center dot 2Cl] was more effective on the PC-3 cell lines and was more effective by triggering apoptosis in the cells.