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Öğe AKT-mediated phosphorylation of TWIST1 is essential for breast cancer cell metastasis(Tubitak Scientific & Technological Research Council Turkey, 2020) Ertosun, Mustafa Gokhan; Pehlivanoglu, Suray; Dilmac, Sayra; Tanriover, Gamze; Ozes, Osman NidaiPreviously, it was shown that human TWIST1 (basic helix-loop-helix (b-HLH) is phosphorylated by Akt kinase at S42, T121, and S123. To show in vivo effect of these phosphorylations, we created mouse TWIST1 expression vector and converted the codons of S42, T125, and S127 to unphosphorylatable alanine and phosphorylation mimicking Glutamic acid. We hypothesized that alanine mutants would inhibit the metastatic ability of 4T1 cells while glutamic acid mutants would convert nonmetastatic 67NR cells into metastatic phenotype. To confirm this hypothesis, we created metastatic 4T1 and nonmetastatic 67NR cells expressing alanine mutants and glutamic acid mutants mouse TWIST1, respectively. Then, we injected 1 x 10(6) 67NR and 1 x 10(5) 4T1 cells overexpressing mutants of TWIST1 into the breast tissue of BALB/c mice. At the end of the 4th week, we sacrificed the animals, determined the numbers of tumors at lungs and liver. Although 67NR cells overexpressing wild-type TWIST1 did not show any metastasis, cells overexpressing S42E and T125E mutants showed 15-30 macroscopic metastasis to liver and lungs. Parallel to this, 4T1 cells expressing S42A and T125A mutants of TWIST1 showed no macroscopic metastasis. Our results indicate that phosphorylation of S42 and T125 by AKT is essential for TWIST1-mediated tumor growth and metastasis.Öğe Anti-proliferative and apoptotic effects of green synthesized silver nanoparticles using Lavandula angustifolia on human glioblastoma cells(Springer Heidelberg, 2021) Simsek, Aysel; Pehlivanoglu, Suray; Acar, Cigdem AydinIn this study, we aimed at the green synthesis of silver nanoparticles (AgNPs) using Lavandula angustifolia extract and the investigation of the anti-proliferative and apoptotic inducing effects of these nanoparticles in the U87MG glioblastoma cancer cell line. Green synthesized silver nanoparticles were characterized by various analytical techniques such as UV-Visible Spectrophotometer (UV-Vis), scanning electron microscopy (SEM) and Energy Dispersive X-ray (EDX). UV-Vis spectroscopy displayed a specific silver plasmon peak at 430 nm. U87MG cells were treated at increased concentrations with Lavandula angustifolia-AgNPs (La-AgNPs) (0-20 mu g/mL) for 72 h and the anti-proliferative effects of green synthesized silver nanoparticles on U87MG cells were evaluated by MTT assay. The La- AgNPs induced a statistically significant dose-dependent decrease in proliferation and increased cytotoxicity in U87MG cells. The IC50 value is 7.536 mu g/mL. Furthermore, the expression of apoptosis proteins caspase-3, caspase-8 and caspase-9 was analyzed using ELISA and caspase-3 and p53 using western blotting. The results suggest that La-AgNPs induce cell death in U87MG cells through the p53 mediated intrinsic apoptotic pathway. Together, the present findings suggest that La-AgNPs could be considered as a potential option for the treatment of glioblastoma.Öğe Anticancer Effects of Vitis vinifera L. Mediated Biosynthesized Silver Nanoparticles and Cotreatment with 5 Fluorouracil on HT-29 Cell Line(Springernature, 2022) Salman, Giray; Pehlivanoglu, Suray; Acar, Cigdem Aydin; Yesilot, SukriyeThe aim of this study was to evaluate the anticancer effects of biosynthesized silver nanoparticles (Vv-AgNPs) from grape (Vitis vinifera L.) seed aqueous extract, alone or in combination with 5-Fluorouracil (5-FU) on HT-29 cell line. Vv-AgNPs were characterized by techniques such as UV-vis spectrophotometer (surface plasmon peak 454 nm), scanning electron microscopy (SEM), and energy-dispersive X-ray spectroscopy (EDX). HT-29 cells were treated with different concentrations (0-80 mu g/mL for MTT) and (0-20 mu g/mL for BrdU) of Vv-AgNPs alone and combined with (200 mu g/mL) 5-FU for 72 h. The cytotoxic effects were analyzed by [3-(4,5-dimethylthiazol-2- yl)-2,5-diphenyl tetrazolium bromide] (MTT) assay (IC50 values 13.74 and 5.35 mu g/mL, respectively). Antiproliferative effects were examined 5-bromo-2'-deoxyuridine (BrdU) assay (IC50 values 9.65 and 5.00 mu g/mL, respectively). Activation of caspase-3 and protein expression levels of p53 were determined by Western blotting analysis. It was observed that Vv-AgNPs significantly increased the cleavage of the proapoptotic proteins caspase 3 and obviously enhanced the expression of p53 in a dose-dependent manner. The increased amount of total oxidant status (TOS) in the 10 mu g/mL Vv-AgNPs + 5-FU treatment group, despite the increasing amount of total antioxidant status (TAS), caused an increase in Oxidative Stress Index (OSI) compared to the control. In this study, it has been shown in vitro that the use of successfully biosynthesized Vv-AgNPs in combination with 5-FU exhibits synergistic cytotoxic, antiproliferative, apoptotic, and oxidative effects against HT-29 cell line.Öğe Anticancer, antimicrobial, spectral, voltammetric and DFT studies with Cu(II) complexes of 2-hydroxy-5-methoxyacetophenone thiosemicarbazone and its N(4)-substituted derivatives(Elsevier Science Sa, 2017) Turkkan, Ercan; Sayin, Ulku; Erbilen, Nesibe; Pehlivanoglu, Suray; Erdogan, Gokce; Tasdemir, Halil Ugur; Saf, Ahmet OzgurNew copper complexes of 2-hydroxy-5-methoxyacetophenone thiosemicarbazone and its N(4)-substituted derivatives were synthesized and characterized by theoretical DFT studies and experimental UV-Vis, FT-IR, EPR spectral analysis, cyclic voltammetry, magnetic susceptibility and conductivity measurements. The DFT calculation results have been used to predict and interpret the experimental results. The geometric parameter G within the range of 7.61-7.86 for all complexes confirms the mononuclear nature of the complexes. The EPR, UV-Vis, DFT studies and obtained bonding parameters show that all the complexes have square planar geometry and their M-L bonds have strong ionic and some in-plane a-bond character. In addition, the experimental and DFT studies showed that HOMO and LUMO energy levels of the complexes may present good electron transporting properties. Also, the investigated Cu(II) complexes were tested for biological activity, proving both in vitro antibacterial and anticancer activity. The complexes exhibited antibacterial activity against Gram positive bacteria S. aureus while exhibiting no activities against gram negative bacteria E. toll and S. gallinarum. The f parameters obtained experimentally by EPR support the antimicrobial activity properties results of the complexes. The evaluations of potential anticancer activity of these complexes were carried out against highly metastatic MDA-MB-231 breast adenocarcinoma cell line by MTT assay. Our results suggest that all tested copper complexes have high cytotoxic effects with the range of 1.76-3.53 mu M IC50 values in vitro. These copper complexes could be considered as potential anticancer agents to counteract drug resistance of metastatic cancer cells. (C) 2016 Elsevier B.V. All rights reserved.Öğe Characterization of green synthesized flaxseed zinc oxide nanoparticles and their cytotoxic, apoptotic and antimigratory activities on aggressive human cancer cells(Taylor & Francis Inc, 2021) Pehlivanoglu, Suray; Acar, Cigdem Aydin; Donmez, SonerThis study was done of green synthesized zinc oxide nanoparticles (ZnO NPs) by using flaxseed extract (Linum usitatissimum L.) and investigated their potential anticancer effects. The ZnO NPs were characterized by UV-Vis, SEM/EDS, and XRD techniques. These analyses showed that these NPs were spherically shaped with a 23-55 nm size range. The cytotoxicity of NPs was confirmed by MTT assay against A549, HT29, and MDA-MB-231 cancer cells, indicating their antiproliferative effect (IC50 values: 68.3, 66.3, and 58.8 mu g/mL, respectively). The apoptotic induction was analyzed by ELISA, and the results showed that the NPs induced apoptosis through caspase-3/9 activation but not by caspase-8. These NPs significantly trigger the intrinsic-apoptotic pathway. Moreover, they exhibited strong antimigratory properties on the lowly metastatic HT29 and the highly metastatic A549 and MDA-MB-231 cells. This is the first report of Linum usitatissimum L-mediated synthesis of ZnO NPs that could be considered as potential antineoplastic agents.Öğe Cognitive Functions and Serum BDNF, GDNF, VEGF, Phoenixin-20 and IL-12 Levels of Half-Marathon Runners Aged 50 and Over(Wiley, 2023) Sen, Aysu; Yargic, Melda Pelin; Celen, Murat Cenk; Pehlivanoglu, Suray; Kostak, Feyza; Karakus, Behiye Nur; Kiziltan, Erhan[Abstract Not Availabe]Öğe Cytotoxic effects, microbiological analysis and inhibitory properties on carbonic anhydrase isozyme activities of 2-hydroxy-5-methoxyacetophenone thiosemicarbazone and its Cu(II), Co(II), Zn(II) and Mn(II) complexes(Springer, 2021) Ucar, Asuman; Findik, Mukerrem; Kuzu, Muslum; Pehlivanoglu, Suray; Sayin, Ulku; Sayin, Zafer; Akgemci, Emine GulerMetal complexes of thiosemicarbazones have been receiving considerable attention in biological applications such as antimicrobial and anticancer therapies. In this work, Co(II), Zn(II) and Mn(II) complexes of 2-hydroxy-5-methoxyacetophenone thiosemicarbazone (HMAT) were synthesized for the first time and characterized by EPR, FT-IR, NMR, UV-Vis spectroscopies, TG/DSC and elemental analysis. X-ray powder diffraction analysis was carried out for Zn(II) complex. HMAT and its Cu(II), Co(II), Zn(II) and Mn(II) complexes were tested as enzyme inhibitory agents. All compounds are effective inhibitor of cytosolic carbonic anhydrase I and II isoforms (hCA I and II) enzymes. IC(50)values of HMAT and its Cu(II), Co(II), Zn(II) and Mn(II) complexes were determined as 93.35, 324.46, 25.67, 1.06 and 22.36 mu M for CA I isozyme and 99.02, 86.64, 57.76, 10.34 and 36.48 mu M for CA II isozyme, respectively. The evaluation of potential cytotoxic effects of the compounds was performed against normal epithelial breast mammary gland CRL-4010, estrogen-positive low metastatic MCF-7 and triple negative highly metastatic MDA-MB-231 breast adenocarcinoma cell lines by MTT assay. The results showed that the tested metal complexes have high cytotoxic effects than their ligand molecule. In particular, the Cu(II) complex displayed preciously high cytotoxic properties different from the others. Given these facts, the Cu(II) complex could be debated as potential chemotherapeutic molecule against drug-resistant breast cancer cells. Minimum inhibitory concentrations of the compounds against the test organisms were also detected for the microbiological analysis.Öğe Determining Stable Structure and in Vitro Antiproliferative Properties of a Novel 3-(2-((4-Trifluoromethyl)phenyl)amino)thiazol-4-yl)-2H-chromen-2-one Molecule(Wiley-V C H Verlag Gmbh, 2023) Sariguney, Ahmet Burak; Sarikaya, Ebru Karakas; Pehlivanoglu, SuraySince coumarin and thiazole derivatives are known to have antioxidant properties, a novel derivative was synthesized in this article. 3-(2-((4-(trifluoromethyl)phenyl)amino)thiazol-4-yl)-2H-chromen-2-one (ATC) was synthesized as a novel compound with high yield and characterized by Raman, FT-IR, C-13-NMR, and H-1-NMR spectroscopic procedures and DFT calculations. In this study, the potential in vitro antiproliferative properties of the ATC compound were evaluated on colorectal cancer (HT29) and melanoma (SK-MEL-30) cell lines. According to the results, the compound was found to be significantly active, approximately 2.6-fold, against melanoma cells compared to healthy fibroblast (L929) cells. Unlike melanoma cells, the compound did not have any adverse effects on colorectal cancer cells. Due to these findings, the compound can be harnessed as a promising antiproliferative drug candidate for preclinical studies against melanoma.Öğe Differential expression pattern of Twist1 in mouse preimplantation embryos suggests its multiple roles during early development(Springer/Plenum Publishers, 2016) Sozen, Berna; Pehlivanoglu, Suray; Demir, NecdetThe purpose of the present study is to understand Twist-related protein 1 (Twist1) spatiotemporal expression patterns and functions during early embryo development. We performed whole-mount double immunofluorescence staining and reverse transcription (RT)-PCR analysis of the Twist1 protein and gene throughout the preimplantation development in mice. We determined that after compaction, the expression of Twist1 becomes developmentally differentiated and targeted in the inner cells of embryos. In blastocysts at E4.5, uniform staining of the inner cell mass was apparent, and it had been gradually translocated to the nucleus of hatched embryonic cells at E4.75. Furthermore, the effect of potential regulators of Twist on its expression level during blastocyst development was also sought. Accordingly, Twist1 expression appeared to be upregulated in both mRNA and protein level following culture of embryos in the presence of high glucose. Our study revealed the dynamic Twist localization within the early stage of embryo. The results are discussed in terms of potential roles of Twist1 in the processes of lineage segregation, hatching, and implantation in post-compaction embryos and in blastocysts.Öğe Epithelial mesenchymal transition regulator TWIST1 transcription factor stimulates glucose uptake through upregulation of GLUT1, GLUT3, and GLUT12 in vitro(Springer, 2021) Pehlivanoglu, Suray; Sahan, Ozge Burcu; Pehlivanoglu, Sebnem; Kont, Kadriye AktasTWIST1 is a major regulator of epithelial mesenchymal transition process, essential in cancer metastasis. Cancer cells increase glucose uptake capabilities to meet their high energy requirements. In this study, we explored the potential role of TWIST1 on glucose transport into the 293T cells in an insulin-dependent and insulin-independent manner. For this purpose, the ectopic expression of TWIST1 was successfully performed by electroporation. The altered mRNA expressions of GLUT-1, -3, -4, and -12, insulin receptor (InsR), and insulin receptor substrate (IRS)-1 and -2 were assessed in control and TWIST1-overexpressing cells. Glucose uptake rates of the cells were evaluated by fluorometric glucose uptake assay. Our findings showed that the transcriptional expression levels of GLUT-1, -3, and -12 genes were significantly upregulated by TWIST1. However, TWIST1 did not alter the mRNA and protein expressions of the InsR, its substrates (IRS-1 and -2), and GLUT-4 genes in 293T cells which are main factors for insulin-stimulated glucose uptake pathway. Also, the glucose transport activities were significantly increased in TWIST1-overexpressing cells compared to controls due to fetal bovine serum (FBS) stimulation, but there was a slight non-significant difference in insulin stimulation. Thus, our data suggest that TWIST1 could promote glucose uptake independently of insulin and is possible to be evaluated as a metabolic marker in cancer. Further investigations are needed to clarify the precise molecular mechanisms underlying the cells' glucose uptake and consumption during tumorigenesis.Öğe Extracellular factors of probiotic bacteria promote immunomodulatory effects of bone marrow mesenchymal stem cells(Wiley, 2021) Yilmaz, Gizem; Pehlivanoglu, Suray[Abstract Not Availabe]Öğe Green and eco-friendly biosynthesis of zinc oxide nanoparticles using Calendula officinalis flower extract: Wound healing potential and antioxidant activity(Wiley, 2023) Acar, Cigdem Aydin; Gencer, Muhammet Abdurrahim; Pehlivanoglu, Suray; Yesilot, Sukriye; Donmez, SonerThis study aimed to produce zinc oxide nanoparticles with Calendula officinalis flower extract (Co-ZnO NPs) using the green synthesis method. In addition, the antioxidant and wound healing potential of synthesized ZnO NPs were evaluated. The absorbance band at 355 nm, which is typical for ZnO NPs, was determined from the UV-Vis absorbance spectrum. The energy-dispersive X-ray spectroscopy (EDS) measurements revealed a high zinc content of 42.90%. The x-ray diffractometer data showed Co-ZnO NPs with an average crystallite size of 17.66 nm. The Co-ZnO NPs did not have apparent cytotoxicity up to 10 mu g/mL (IC50 25.96 mu g/mL). C. officinalis ZnO NPs showed partial cell migration and percent wound closure (69.1%) compared with control (64.8%). In addition, antioxidant activities of Co-ZnO NPs with 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and 2,2 diphenyl-1 picrylhydrazil (DPPH) were evaluated and radical scavenging activity of 33.49% and 46.63%, respectively, was determined. These results suggest that C. officinalis extract is an effective reducing agent for the green synthesis of ZnO NPs with significant antioxidant and wound healing potential.Öğe Identification of novel mutations of Insulin Receptor Substrate 1 (IRS1) in tumor samples of non-small cell lung cancer (NSCLC): Implications for aberrant insulin signaling in development of cancer(Soc Brasil Genetica, 2019) Gorgisen, Gokhan; Hapil, Fatma Zehra; Yilmaz, Ozlem; Cetin, Zafer; Pehlivanoglu, Suray; Ozbudak, Irem Hicran; Erdogan, AbdullahLung cancer is the leading cause of cancer-related death, and NSCLC constitutes nearly 85%-90% of all cases. The IRS proteins function as adaptors and transmit signals from multiple receptors. Upon binding of insulin to the insulin receptor (IR), IRS1 is phosphorylated at several YXXM motifs creating docking sites for the binding of PI3Kp85, which activates AKT kinase. Therefore, we thought that gain of function mutantions of IRS1 could be related to development of lung cancer. In line with this, we wanted determine whether the IRS1 gene was mutated in the coding regions surrounding YXXM motifs. We sequenced the coding regions surrounding YXXM motifs of IRS1 using tumor samples of 42 NSCLC patients and 40 matching controls and found heterozygote p.S668T mutation in nine of 42 samples and four of nine also had the p.D674H mutation. We generated IRS1 expression vectors harboring p.S668T, p.D674H and double mutants. Expression of the mutants differentially affected insulin-induced phosphorylation of IRS1, AKT, ERK, and STAT3. Also, our mutants induced proliferation, glucose uptake, inhibited the migration of 293T cells and affected the responsiveness of the cells to cisplatin and radiation. Our results suggest that these novel mutations play a role in the phenotype of lung cancer.Öğe Identification of novel mutations of Insulin Receptor Substrate 1 (IRS1) in tumor samples of non-small cell lung cancer (NSCLC): Implications for aberrant insulin signaling in development of cancer(Soc Brasil Genetica, 2019) Gorgisen, Gokhan; Hapil, Fatma Zehra; Yilmaz, Ozlem; Cetin, Zafer; Pehlivanoglu, Suray; Ozbudak, Irem Hicran; Erdogan, AbdullahLung cancer is the leading cause of cancer-related death, and NSCLC constitutes nearly 85%-90% of all cases. The IRS proteins function as adaptors and transmit signals from multiple receptors. Upon binding of insulin to the insulin receptor (IR), IRS1 is phosphorylated at several YXXM motifs creating docking sites for the binding of PI3Kp85, which activates AKT kinase. Therefore, we thought that gain of function mutantions of IRS1 could be related to development of lung cancer. In line with this, we wanted determine whether the IRS1 gene was mutated in the coding regions surrounding YXXM motifs. We sequenced the coding regions surrounding YXXM motifs of IRS1 using tumor samples of 42 NSCLC patients and 40 matching controls and found heterozygote p.S668T mutation in nine of 42 samples and four of nine also had the p.D674H mutation. We generated IRS1 expression vectors harboring p.S668T, p.D674H and double mutants. Expression of the mutants differentially affected insulin-induced phosphorylation of IRS1, AKT, ERK, and STAT3. Also, our mutants induced proliferation, glucose uptake, inhibited the migration of 293T cells and affected the responsiveness of the cells to cisplatin and radiation. Our results suggest that these novel mutations play a role in the phenotype of lung cancer.Öğe Microwave-assisted biofabrication of silver nanoparticles using Helichrysum arenarium flower extract: characterization and biomedical applications(Springer Heidelberg, 2023) Acar, Cigdem Aydin; Pehlivanoglu, Suray; Yesilot, Sukriye; Uzuner, Sezin YakutIn the treatment of melanoma, the prevention of metastasis and elimination of the risk of infection due to chemotherapy are of great importance. Therefore, the goal of this study was to develop an alternative treatment method with antibacterial properties for melanoma. Silver nanoparticles (AgNPs) were obtained by the biological method using Helichrysum arenarium flower extract in an easy, low-cost, and environmentally friendly manner. Characterization of synthesized AgNPs was performed using a UV-visible spectrophotometer (UV-Vis), scanning electron microscope (SEM), and energy-dispersive X-ray spectroscopy (EDS). The melanoma (SK-MEL-30) cancer cell line was used to determine the anticancer and antimetastatic activity of AgNPs synthesized with H. arenarium (Ha-AgNPs) extract. Cytotoxicity was tested with a fibroblast cell line (L929). Cell viability was determined by MTT assay, antioxidant activity by H2O2 radical scavenging assay, antibacterial activity by the disc diffusion method, and biocompatibility by the hemolysis test. Ha-AgNPs showed a maximum peak at 427 nm absorbance. The elemental composition of Ha-AgNPs was determined by EDS, and the existence of silver was confirmed. The biosynthesized Ha-AgNPs significantly inhibited the growth of medically important pathogenic, Gram-negative multidrug-resistant Escherichia coli, Gram-positive Staphylococcus aureus, and Gram-positive multidrug-resistant Enterococcus faecalis. MTT assay revealed dose-dependent manner anticancer activity of Ha-AgNPs on SK-MEL-30 (melanoma cancer cell line) cells in the concentration range of 0-100 mu g/mL (IC50 value: 35.52 mu g/mL). The cytotoxicity assay on L929 cells revealed no adverse effects of Ha-AgNPs on healthy cells in the concentration range of 0-25 mu g/mL (IC50: 47.9 mu g/mL). Additionally, antioxidant activity and biocompatibility of Ha-AgNPs were evaluated. AgNPs synthesized by H. arenarium have a promising future as a potent anticancer and antimetastatic agent with antibacterial properties.Öğe New copper(II) complex based-thiosemicarbazone and phenanthroline: DNA/BSA binding, antiproliferative activity, DFT and docking studies(Elsevier, 2023) Findik, Mukerrem; Turkkan, Ercan; Pehlivanoglu, Suray; Sayin, Ulku; Ceylan, Umit; Akgemci, Emine GulerA new copper(II) complex {Cu(HPP)}, bromo(1,10-phenanthroline)(triphenylphosphine)copper(I) with 2-hydroxy-5-methoxyacetophenone thiosemicarbazone (HMAT) was synthesized and characterized by experimental FT-IR, Raman, UV-vis, TGA and EPR spectral analysis. The Cu(HPP) was theoretically modeled using the B3LYP/VTZ method/basis set and the values of the spectroscopic parameters were calculated by the DFT method. The coordination geometry around the Cu(II) in the compound was predicted as an elongated octahedral. Spectroscopic investigations showed the intercalative binding mechanism of the Cu(HPP) with calf-thymus deoxyribonucleic acid (ct-DNA). Spectroscopic techniques were also used to evaluate the interaction of the Cu (HPP) with bovine serum albumin (BSA), which revealed that the Cu(HPP) could bind to BSA significantly. In addition, the molecular docking between the Cu(HPP) and BSA was investigated to support the bonding mechanism. Further, we studied the anticancer activity of the Cu(HPP) in drug resistant breast cancer cell line (MDA-MB-231), with a focus on the proliferative characteristics. Our findings emphasize that this newly synthetized complex has a significant cytotoxic effect on the cells and can be utilized as a candidate chemotherapeutic agent to effectively target breast cancer.Öğe The Role of Zinc Status on Spatial Memory, Hippocampal Synaptic Plasticity, and Insulin Signaling in icv-STZ-Induced Sporadic Alzheimer's-Like Disease in Rats(Springernature, 2022) Baltaci, Saltuk Bugra; Unal, Omer; Gulbahce-Mutlu, Elif; Gumus, Haluk; Pehlivanoglu, Suray; Yardimci, Ahmet; Mogulkoc, RasimAlzheimer's disease (AD), especially its sporadic form (sAD), is of multifactorial nature. Brain insulin resistance and disrupted zinc homeostasis are two key aspects of AD that remain to be elucidated. Here, we investigated the effects of dietary zinc deficiency and supplementation on memory, hippocampal synaptic plasticity, and insulin signaling in intracerebroventricular streptozotocin (icv-STZ)-induced sAD in rats. The memory performance was evaluated by Morris water maze. The expression of hippocampal protein and mRNA levels of targets related to synaptic plasticity and insulin pathway was assessed by Western blot and real-time quantitative PCR. We found memory deficits in icv-STZ rats, which were fully recovered by zinc supplementation. Western blot analysis revealed that icv-STZ treatment significantly reduced hippocampal PSD95 and p-GSK3 beta, and zinc supplementation restored the normal protein levels. mRNA levels of BDNF, PSD95, SIRT1, GLUT4, insulin receptor, and ZnT3 were found to be reduced by icv-STZ and reestablished by zinc supplementation. Our data suggest that zinc supplementation improves cognitive deficits and rescues the decline in key molecular targets of synaptic plasticity and insulin signaling in hippocampus caused by icv-STZ induced sAD in rats.Öğe Synthesis of anti-4-phenoxyphenylaminoglyoxime and its some transition metal complexes: Spectral, DFT, electrochemical and anticancer activity studies(Elsevier, 2020) Findik, Mukerrem; Ucar, Asuman; Turkkan, Ercan; Pehlivanoglu, Suray; Ozcan, Emineanti-4-phenoxyphenylaminoglyoxime (LH2) was synthesized starting from 4-aminodiphenylether and anti-chloroglyoxime in absolute ethanol. Then, mononuclear complexes [Ni(II) and Cu(II)] of LH2 were synthesized with the metal:ligand ratio of 1:2. The LH2 and its complexes [Ni(LH)(2) and Cu(LH)(2)] were characterized by elemental analysis, FT-IR, Raman, UV-vis, thermogravimetric analysis (TGA), H-1 NMR, C-13 NMR, heteronuclear multiple bond correlation (HMBC) spectroscopy and theoretical DFT studies. Also, redox properties of the ligand and its complexes were investigated by cyclic voltammetry in DMSO solution at room temperature. Conformational space was scanned with molecular mechanic simulations and then the possible stable conformers of LH2 ligand were determined by B3LYP/6-311++G (d,p) level calculations. The Ni(LH)(2) and Cu(LH)(2) metal complexes were modeled theoretically using B3LYP/LanL2DZ level. The theoretical vibrational frequencies were calculated by using optimization calculation levels. The NMR parameters of LH2 ligand, Cu(LH)(2) and Ni(LH)(2) metal complexes were calculated at mPW1PW91/6-311 + G (2d,p) level. Theoretically calculated values were compared with the related experimental values. The DFT calculation results have been used to predict and interpret the molecular structures of LH2 ligand and its complexes. The geometry around nickel in Ni(LH)(2) and around cupper in Cu(LH)(2) complex are almost square planar. In addition, we evaluated the efficacy of LH2 ligand and its Ni(LH)(2) and Cu(LH)(2) complexes in the breast adenocarcinoma cell line (MCF7). Our data showed that the metal compounds affect positively the cytotoxic activity of the ligand (LH2). The metal complexes, especially Ni(LH)(2) complex, exhibited noteworthy biological activity against the viability of MCF7 cells. (C) 2020 Elsevier B.V. All rights reserved.Öğe Synthesis of Carbazole-Substituted thiosemicarbazone and its Cu(II) Complex, DNA/Protein Binding, Cytotoxic, antiproliferative activities and molecular docking studies(Elsevier, 2023) Findik, Mukerrem; Kuzu, Burak; Pehlivanoglu, Suray; Kaya, Serdal; Sayin, Ulku; Akgemci, Emine Guler; Saf, Ahmet OzgurIn this study, 9-ethyl-3-carbazolecarboxaldehyde-4-ethyl-thiosemicarbazone (ECCAET) and its copper(II) com-plex (Cu(ECCAET)2) were firstly synthesized and characterized. DFT and EPR studies confirmed that the complex is mononuclear and has square planar geometry. The interaction of all synthesized compounds with calf thymus DNA (CT-DNA) was examined by absorption and fluorescent spectroscopy. The experimental results showed that Cu(ECCAET)2 interacts with DNA via an intercalative binding mode. The binding interactions of the complex with CT-DNA have been confirmed through viscosity measurements revealing that the complex interacts with DNA via intercalation. Furthermore, the protein binding ability of ECCAET and Cu(ECCAET)2 was investigated using BSA via electronic absorption spectral titration, fluorescence quenching, and synchronous fluorescence spectrum studies, which revealed that the Cu(ECCAET)2 strongly bound to BSA over the ligand. Molecular docking studies were also performed to support the bonding mechanism of ECCAET and Cu(ECCAET)2 with DNA and BSA. The biological activity studies of ECCAET and Cu(ECCAET)2 against cancer cells were also investigated. A panel of cancer cell lines, including A2780 human ovarian adenocarcinoma, MDA-MB-231 human triple-negative breast adenocarcinoma, and as a control non-cancerous L929 fibroblast cell lines were also used to test the compounds' anticancer activities. Cytotoxic and antiproliferative properties of Cu(ECCAET)2 were visibly higher than its ligand (ECCAET) for all tested cell lines. The Cu(ECCAET)2 had a distinctive biological effects on A2780, and MDA-MB-231 cells compared to non-cancerous cells. Within these results, Cu(ECCAET)2 was found a promising drug candidate against gynecologic cancer diseases.
