Person: BİNGÖL ÖZAKPINAR, ÖZLEM
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BİNGÖL ÖZAKPINAR
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ÖZLEM
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Publication Open Access Synthesis and Characterization of Celecoxib Derivatives as Possible Anti-Inflammatory, Analgesic, Antioxidant, Anticancer and Anti-HCV Agents(MDPI, 2013-03-21) ŞENER, AZİZE; Kucukguzel, S. Guniz; Coskun, Inci; Aydin, Sevil; Aktay, Goknur; Gursoy, Sule; Cevik, Ozge; Ozakpinar, Ozlem Bingol; Ozsavci, Derya; Sener, Azize; Kaushik-Basu, Neerja; Basu, Amartya; Talele, Tanaji T.A series of novel N-(3-substituted aryl/alkyl-4-oxo-1,3-thiazolidin-2-ylidene)-4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl] benzenesulfonamides 2a-e were synthesized by the addition of ethyl alpha-bromoacetate and anhydrous sodium acetate in dry ethanol to N-(substituted aryl/alkylcarbamothioyl)-4-[5-(4-methylphenyl)-3-(trifluoro-methyl)- 1H-pyrazol-1-yl] benzene sulfonamides 1a-e, which were synthesized by the reaction of alkyl/aryl isothiocyanates with celecoxib. The structures of the isolated products were determined by spectral methods and their anti-inflammatory, analgesic, antioxidant, anticancer and anti-HCV NS5B RNA-dependent RNA polymerase (RdRp) activities evaluated. The compounds were also tested for gastric toxicity and selected compound 1a was screened for its anticancer activity against 60 human tumor cell lines. These investigations revealed that compound 1a exhibited anti-inflammatory and analgesic activities and further did not cause tissue damage in liver, kidney, colon and brain compared to untreated controls or celecoxib. Compounds 1c and 1d displayed modest inhibition of HCV NS5B RdRp activity. In conclusion, N-(ethylcarbamothioyl)-4-[5-(4-methylphenyl)- 3-(trifluoromethyl)-1H-pyrazol-1-yl] benzenesulfonamide (1a) may have the potential to be developed into a therapeutic agent.Publication Metadata only Investigation of the protective effect of gel incorporating Eugenia jambolana leaf extract on 5-fluorouracil-induced oral mucositis: an animal study(2022-08-01) BİNGÖL ÖZAKPINAR, ÖZLEM; ARICIOĞLU, FEYZA; AKSOY N., Sen E., Sukmasari S., BİNGÖL ÖZAKPINAR Ö., ARICIOĞLU F., YÜCEL Y. Y., Dumlu M. R., Doolaanea A. A., AbdulRahman M. N., OLGAÇ N. V., et al.Purpose The study aimed to evaluate the possible preventive effect of two concentrations (3 and 5% w/w) of Eugenia jambolana (EJ) extract against 5-FU-induced mucositis. Method Sixteen adult rats were separated into four groups: two control and two preventive groups. Animals in Groups 1, 2, and 3 were injected intraperitoneally with 60 mg/kg/day of 5-FU on Day 1 followed by 150 mg/kg/day on Day 5. The rats in Group 4 (negative control) were given physiological saline at the same times and doses. Furthermore, on the fifth day of the study, the cheek and sublingual mucosa were irritated by external superficial scratches using the tip of an 18-G needle, followed by the application 15 mu L of 20% acetic acid, after which 3 and 5% EJ w/w gels were applied topically for animals in Groups 2 and 3, respectively. Results The weight and the mucositis scores were recorded. Antioxidant and anti-inflammatory markers and biochemical tests were analyzed. Significant differences were found between the study groups in weight loss, clinical mucositis scores, mortality rates, and antioxidant and anti-inflammatory parameters. Conclusion The preventive effect of 3% gel was significant, with no mortality rate, making it an option for preventive strategies.Publication Metadata only Synthesis of Diflunisal Thiazolidinones as Anticancer Agents(BENTHAM SCIENCE PUBL LTD, 2016) ŞENER, AZİZE; Senkardes, Sevil; Ozakpinar, Ozlem B.; Ozsavci, Derya; Sener, Azize; Cevik, Ozge; Kucukguzel, S. GunizA series of diflunisal 4-thiazolidinones were synthesized. Some selected compounds were determined at one dose towards the full panel of 60 human cancer cell lines by National Cancer Institute. 2',4'-Difluoro-4-hydroxy-N-[4-oxo-2-(thiophen-2-yl)-1,3-thiazolidin-3-yl]biphenyl-3-carboxamide (4a) demonstrated the most marked effect on K-562 cancer cell line with 58.59 % growth inhibition at 10 mu M. Compound 4a was evaluated in vitro using the MTT colorimetric method against human leukemia cell line K-562 and mouse embryonic fibroblasts cell line NIH-3T3 at different doses for cell viability and growth inhibition. Compound 4a exhibited anticancer activity with IC50 value of 5.2 mu M against K-562 cells and did not display cytotoxicity towards NIH-3T3 cells compared with diflunisal. In addition, this compound could be an interesting prototype as an antiproliferative agent.Publication Open Access Apocynin reduces cytotoxic effects of monosodium glutamate in the brain: A spectroscopic, oxidative load, and machine learning study(2022-10-15) BİNGÖL ÖZAKPINAR, ÖZLEM; Depciuch J., Jakubczyk P., Paja W., Sarzyński J., Pancerz K., AÇIKEL ELMAS M., Keskinöz E., BİNGÖL ÖZAKPINAR Ö., ARBAK S., Özgün G., et al.© 2022 Elsevier B.V.Herein, we examined the modulatory effects of Apocynum (APO) on Monosodium Glutamate (MSG)-induced oxidative damage on the brain tissue of rats after long-term consumption of blood serum components by biochemical assays, Fourier transform infrared spectroscopy (FTIR), and machine learning methods. Sprague-Dawley male rats were randomly divided into the Control, Control + APO, MSG, and MSG + APO groups (n = 8 per group). All administrations were made by oral gavage saline, MSG, or APO and they were repeated for 28 days of the experiments. Brain tissue and blood serum samples were collected and analyzed for measurement levels of malondialdehyde (MDA), glutathione (GSH), myeloperoxidase (MPO), superoxide dismutase (SOD) activity, and Spectroscopic analysis. After 29 days, the results were evaluated using machine learning (ML). The levels of MDA and MPO showed changes in the MSG and MSG + APO groups, respectively. Changes in the proteins and lipids were observed in the FTIR spectra of the MSG groups. Additionally, APO in these animals improved the FTIR spectra to be similar to those in the Control group. The accuracy of the FTIR results calculated by ML was 100%. The findings of this study demonstrate that Apocynin treatment protects against MSG-induced oxidative damage by inhibiting reactive oxygen species and upregulating antioxidant capacity, indicating its potential in alleviating the toxic effects of MSG.Publication Open Access Investigation of 3D-printed chitosan-xanthan gum patches(2022-07-01) ALTAN, ERAY; GÜNDÜZ, OĞUZHAN; BİNGÖL ÖZAKPINAR, ÖZLEM; ALTAN E., Turker N., Hindy O. A., Dirican Z., Ozakpinar Ö., Demir A. U., Kalaskar D., Thakur S., GÜNDÜZ O.In this study, using a new polymer combination of Chitosan(CH)/Xanthan Gum(XG) has been exhibited for wound dressing implementation by the 3D-Printing method, which was fabricated due to its biocompatible, biodegradable, improved mechanical strength, low degradation rate, and hydrophilic nature to develop cell-mimicking, cell adhesion, proliferation, and differentiation. Different concentrations of XG were added to the CH solution as 0.25, 0.50, 0.75, 1, and 2 wt% respectively in the formic acid/distilled water (1.5:8.5) solution and rheologically characterized to evaluate their printability. The results demonstrated that high mechanical strength, hydrophilic properties, and slow degradation rate were observed with the presence and increment of XG concentration within the 3D-Printed patches. Moreover, in vitro cell culture research was conducted by seeding NIH 3T3 fibroblast cells on the patches, proving the cell proliferation rate, viability, and adhesion. Finally, 1% XG and 4% CH containing 3D-Printed patches were great potential for wound dressing applications.Publication Metadata only The effect of exogenous oxytocin on streptozotocin (STZ)-induced diabetic adult rat testes(ELSEVIER SCIENCE INC, 2015) BİNGÖL ÖZAKPINAR, ÖZLEM; Koroglu, P.; Senturk, G. Erkanli; Yucel, D.; Ozakpinar, O. Bingol; Uras, F.; Arbak, S.Oxytocin (OXY) plays a crucial role in reproduction. The aim of this study is to investigate the therapeutic and protective effects of oxytocin treatment on streptozotocin (STZ) induced diabetes in testicular tissue. The rats were randomly divided into four experimental groups: (I) Control Group, (II) STZ induced Diabetic Group (STZ Group), (III) STZ induced Diabetic Group with Pre-Oxytocin treatment (Pre-OXY Group) and ( IV) STZ induced Diabetic Group with Post-Oxytocin treatment (Post-OXY Group); each group contains six animals. The rats whose blood glucose levels were more than 200 mg/dl were included to the experiment. At the end of the 4th week, testes tissue samples were taken to be processed for light microscopy and transmission electron microscopy. Malondialdehyde (MDA), Glutathione (GSH) and Advanced Oxidation Protein Products (AOPP) levels were determined biochemically in blood samples. Testicular tissue samples stained with Hematoxylin and Eosin (H&E) and Periodic acid-Schiff (PAS) reaction were evaluated under light microscope. The histopathological damage score of testicular tissue, which was significantly increased in STZ group, was decreased by oxytocin treatment. According to biochemical data, MDA and AOPP levels have been increased in the blood of STZ Group compared to the Control Group whereas they decreased significantly in Oxytocin-treated Groups compared to STZ Group. GSH levels were significantly decreased in the blood of STZ Group and increased in the blood of Oxytocin-treated Groups compared to STZ Group. In conclusion, oxytocin has a potential protective effect on the testes tissue of STZ-induced diabetic rats. (C) 2014 Elsevier Inc. All rights reserved.Publication Metadata only Protective effect of ferulic acid on cisplatin induced nephrotoxicity in rats(ELSEVIER, 2017) OKUYAN, BETÜL; Bami, Erliasa; Ozakpinar, Ozlem Bingol; Ozdemir-Kumral, Zarife Nigar; Koroglu, Kutay; Ercan, Feriha; Cirakli, Zeynep; Sekerler, Turgut; Izzettin, Fikret Vehbi; Sancar, Mesut; Okuyan, BetulThis study aims to determine the potential protective effects of ferulic acid against cisplatin-induced nephrotoxicity and to compare its effect with curcumin, a well-known protective agent against cisplatin- induced toxicity in rats. Administration of cisplatin resulted in high BUN (Blood Urea Nitrogen), creatinine, MDA (Malondialdehyde), MPO (Myeloperoxidase), TOS (Total Oxidative Status), PtNT (Protein Nitrotyrosine) levels (p < 0.05). Histological observations showed abnormal morphology of kidney; in addition with appearance of TUNEL positive cells indicating apoptosis in cisplatin administered group. HO-1 (Heme Oxygenase-1) levels measured by RT-PCR (Real Time Polymerase Chain Reaction), and TAS (Total Antioxidative Status) revealed antioxidant depletion due to cisplatin toxicity in animals (p < 0.05). All parameters showed improvement in groups treated with ferulic acid (p < 0.05). Ferulic acid treatment was found significant in preventing oxidative stress, increasing antioxidative status and regaining histological parameters to normal, indicating nephroprotective and antioxidant effects of this phenolic compound.Publication Open Access Growth Arrest-Specific 6 (Gas6) and TAM Receptors in Mouse Platelets(GALENOS YAYINCILIK, 2015-03-05) BİNGÖL ÖZAKPINAR, ÖZLEM; Uras, Fikriye; Kucuk, Burhanettin; Ozakpinar, Ozlem Bingol; Demir, Ahmet MuzafferObjective: Growth arrest-specific 6 (Gas6) is a newly discovered vitamin K-dependent protein, which is a ligand for TAM receptors [Tyro3 (Sky), Axl, and Mer] from the tyrosine kinase family. Gas6 knockout mice were resistant to venous and arterial thrombosis. There are contradictory reports on the presence of Gas6 and its receptors in mouse platelets. The objective of this study was to investigate whether Gas6 and its receptors were present in mouse platelets or not. Materials and Methods: Specific pathogen-free BALB/c male and female mice of 8-10 weeks old and 25-30 g in weight were anesthetized under light ether anesthesia and blood samples were taken from their hearts. RNAs were isolated from isolated platelets, and then mRNAs encoding Gas6 and TAM receptors were detected by reverse transcription-polymerase chain reaction (RT-PCR). Protein concentrations of Gas6 and TAM receptors in platelets were measured by ELISA, but not those of Mer, because of the absence of any commercial ELISA kit for mouse specimens. Results: RT-PCR results indicated the presence of mRNAs encoding Gas6 and Mer in mouse platelets. However, although RTPCR reactions were performed at various temperatures and cycles, we could not detect the presence of mRNAs encoding Axl and Tyro3 (Sky). Receptor protein levels of Axl and Tyro3 were below the detection limits of the ELISA method. Conclusion: We found the presence of mRNAs encoding Gas6 and the receptor Mer in mouse platelets, but not Axl and Tyro3. Gas6, Axl, and Tyro3 protein levels were below the detection limits of the ELISA. The presence of mRNA is not obvious evidence of protein expression in platelets that have no nucleus or DNA. Further studies are required to clarify the presence of Gas6/TAM receptors in platelets using real-time PCR and more sensitive immunological methods, and future studies on mechanisms will indicate whether the Gas6/TAM pathway is a strategy for treatment of disorders.Publication Open Access Novel 1,2,4-triazoles derived from Ibuprofen: synthesis and in vitro evaluation of their mPGES-1 inhibitory and antiproliferative activity(2022-11-01) BİNGÖL ÖZAKPINAR, ÖZLEM; KULABAŞ, NECLA; TATAR, ESRA; KÜÇÜKGÜZEL, İLKAY; Bulbul B., Ding K., Zhan C., Ciftci G., YELEKÇİ K., Gurboga M., BİNGÖL ÖZAKPINAR Ö., Aydemir E., Baybag D., ŞAHİN F., et al.Some novel triazole-bearing ketone and oxime derivatives were synthesized from Ibuprofen. In vitro cytotoxic activities of all synthesized molecules against five cancer lines (human breast cancer MCF-7, human lung cancer A549, human prostate cancer PC-3, human cervix cancer HeLa, and human chronic myelogenous leukemia K562 cell lines) were evaluated by MTT assay. In addition, mouse embryonic fibroblast cells (NIH/3T3) were also evaluated to determine the selectivity. Compounds 18, 36, and 45 were found to be the most cytotoxic, and their IC50 values were in the range of 17.46-68.76 mu M, against the tested cancer cells. According to the results, compounds 7 and 13 demonstrated good anti-inflammatory activity against the microsomal enzyme prostaglandin E2 synthase-1 (mPGES-1) enzyme at IC50 values of 13.6 and 4.95 mu M. The low cytotoxicity and non-mutagenity of these compounds were found interesting. Also, these compounds significantly prevented tube formation in angiogenesis studies. In conclusion, the anti-inflammatory and angiogenesis inhibitory activities of these compounds without toxicity suggested that they may be promising agents in anti-inflammatory treatment and they may be supportive agents for the cancer treatment.Publication Open Access Synthesis and anticancer activity of novel hydrazone linkage-based aryl sulfonate derivatives as apoptosis inducers(SPRINGER BIRKHAUSER, 2022-02) BİNGÖL ÖZAKPINAR, ÖZLEM; Senkardes, Sevil; Han, M. Ihsan; Gurboga, Merve; Ozakpinar, Ozlem Bingol; Kucukguzel, S. GunizIn the present study, the various 28 hybrid molecules containing hydrazone and sulfonate moieties were synthesized and characterized by FTIR, H-1-NMR, C-13-NMR spectroscopy and LC-MS spectrometry, besides elemental analysis. The compounds were evaluated for their antiproliferative effects against six cancer cell lines, namely A549 (non-small cell lung cancer), MCF-7 (breast cancer), HT-29 (colorectal adenocarcinoma cancer), PC-3 (androgen-independent prostate adenocarcinoma), Hep3B (hepatocellular carcinoma cancer), and HeLa (epitheloid cervix carcinoma cancer). Among all the target compounds, compounds 4g and 4h exhibited more promising effects on MCF-7 cell lines (IC50 = 17.8 mu M and 21.2 mu M, respectively) with high selectivity. Further mechanistic studies proposed that compounds 4g and 4h induced apoptosis is mediated through the intrinsic apoptotic pathway with changes in mitochondrial membrane potential by finally activating caspase-9 and caspase-3. The results have been encouraging enough to merit further investigation. [GRAPHICS] .