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BENKLİ, KADRIYE

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KADRIYE
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BENKLİ
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Now showing 1 - 7 of 7
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    Gold(III) compounds-mediated inhibition of lung cancer cell proliferation
    (2016-03-01T00:00:00Z) Bostancioglu, Rakibe B.; Kaya, Murat; Koparal, Ayse T.; Benkli, KADRİYE; BENKLİ, KADRIYE
    Research on chemotherapeutics for lung cancer is crucial for designing a new therapeutic strategy against malignant lung tumors. Although radiotherapy and chemotherapy, which are not selective for cancer cells and exert toxic effects on healthy cells, have a limited advantage, they are the primary treatment modalities for non-small lung cancer. In addition to cytotoxicity, resistance of chemotherapeutics results in failure of treatment. This is why it is of utmost importance to focus on the creation of new chemotherapeutics without toxicity for the successful treatment and improved survival of cancer patients. New gold(III) and Pt(II) compounds were synthesized with a heterocyclic ligand using 2-phenylimidazo[4,5-f][1,10]phenanthroline as a ligand and bis-1,4-di[([1,10] phenanthroline-5-il)amino]-2-buten as a bridge molecule. The characterization of the compounds was carried out using a variety of spectroscopic methods (H-1 NMR, IR, MS, and elemental analysis). Their antiproliferative, antitumoral, and apoptotic activities were determined. IR spectra and NMR results confirmed the formation of dinuclear heterocyclic complexes for two metal complexes. Cytotoxicity studies on lung cancer cells (A549) and healthy cells (CHL) showed a marked increase in cytotoxicity with the use of gold(III) complexes, and especially [Au(L)B](PF6)(2) showed higher cytotoxic and apoptotic features than cisplatin at lower concentrations in cancer cells. These findings have been supported by results from DAPI staining and colorimetric measurement of the caspase-3 enzyme in both cell lines. Compounds showed selective toxicity on the cancer cells. In the light of the high efficacy of our newly synthesized gold complexes, they might be good and promising anticancer agents compared with cisplatin.
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    Assessment of in vitro cytotoxic and genotoxic activities of some trimethoprim conjugates
    (2018-06-01) Bayulken, Devrim Guzel; Bostancioglu, R. Beklem; Koparal, A. Tansu; Tuylu, Berrin Ayaz; Dag, AYDAN; Benkli, KADRİYE; DAĞ, AYDAN; BENKLİ, KADRIYE
    Trimethoprim, a commonly used antibacterial agent, is widely applied in the treatment of variety of infections in human. A few studies have demonstrated an extensive exposure of man to antibiotics, but there is still a lack of data for cytotoxic effects including nephrotoxicity, gastrointestinal toxicity, hematotoxicity, neurotoxicity and ototoxicity. The main purpose behind this study was to determine cytotoxic and genotoxic activities of trimethoprim (1), trimethoprim with maleic acid (2) and trimethoprim in conjugation with oxalic acid dihydrate (3). The cytotoxic effects of these three conjugates were elucidated by employing 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoium bromide (MTT) assay using embryonic rat fibroblast-like cell line (F2408) and H-ras oncogene activated embryonic rat fibroblast-like cancer cell line (5RP7). Additionally, determination of genotoxic activity of these three compounds were studied by using cytokinesis blocked micronucleus assay (CBMN) in human lymphocytes. The results demonstrated that trimethoprim alone and its combination with other compounds are able to induce both cytotoxic and genotoxic damage on cultured cells (F2408, 5RP7, human lymphocytes).
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    Apoptotic effects of dipyrido [3,2-a:2 -,3 --c] phenazine (dppz) Au(III) complex against diethylnitrosamine/phenobarbital induced experimental hepatocarcinogenesis in rats
    (2014-08-01T00:00:00Z) Tekin, Neslihan; Ustuner, Mehmet C.; Akyuz, Fahrettin; Ozbayer, Cansu S.; Aydin, Ozlem; Benkli, KADRİYE; Burukoglu, Dilek; Degirmenci, Irfan; Ozden, Hilmi; BENKLİ, KADRIYE
    We evaluated the effects of dipyrido [3,2-a:2-,3--c] phenazine (dppz) Au(III) complex ([Au(dppz)Cl-2]Cl) on apoptosis during chemically induced hepatocellular carcinoma. 48 male Spraque-Dawley rats were divided into six groups; group I (control), group II [Dimethyl sulfoxide (DMSO)], group III ([Au(dppz)Cl-2]Cl), group IV [diethylnitrosamine + Phenobabital (DEN + PB)], group V (DEN + PB + [Au(dppz)Cl-2]Cl (2nd week)), and group VI (DEN + PB + [Au(dppz)Cl-2]Cl (7th week). The rats in groups IV through VI were administrated with DEN in a single dose of intraperitoneal 175 mg/kg. After 2 weeks of DEN administration, these groups of rats were given daily PB in a dose of 500 ppm. In group V, after two weeks of DEN administration, [Au(dppz)Cl-2]Cl complex (2 mg/kg) was given once a week by intraperitoneal injection. In the group VI, the rats were given a dose of 2 mg/kg [Au(dppz)Cl-2]Cl complex once a week, 7 weeks after DEN administration. At the end of the study, blood and tissue samples were collected from the rats to determine levels of serum AST, ALT, and LDH, and caspase 3, p53, Bax, Bcl-2 and DNA fragmentation in liver. AST, ALT, LDH, and Bcl-2 levels were higher in group IV, compared to group I, but caspase 3 and p53 levels were lower. In group V, caspase 3, p53, Bax, and DNA fragmentation levels were higher than those of group IV. Caspase 3 and p53 levels increased in group VI compared with group IV. In conclusion, [Au(dppz)Cl-2]Cl complex induced apoptosis by elevating levels of caspase 3, p53, Bax, and DNA fragmentation.
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    Design and synthesis of novel organometallic complexes using boronated phenylalanine derivatives as potential anticancer agents
    (2019-07-04) Varol, Mehmet; Benkli, KADRİYE; Koparal, Ayse T.; Bostancioglu, Rakibe B.; BENKLİ, KADRIYE
    Drug design and discovery studies are important because of the prevalence of diseases without available medical cures. New anticancer agents are particularly urgent because of the high mortality rate associated with cancer. A series of mononuclear gold (III) and platinum (II) complexes based on boronated phenylalanine (BPA) were designed and synthesized using 4,4--dimethyl-2,2--dipyridyl (L1) or 1,10-phenanthroline-5,6-dion (L2) ligands to obtain promising anticancer drug candidates. Proton nuclear magnetic resonance, infrared, mass spectrometry, and elemental analyses were utilized for chemical characterizations. Cell viability, cancer cell colony formation, endothelial tube formation, and cytoskeleton staining assays were performed using A549 lung adenocarcinoma and human umbilical vein endothelial cells (HUVECs) to investigate preliminary pharmacological activities. L1-based platinum (II) complex (BPA-L1-Pt) was the most promising complex, and has similar activity with the approved chemotherapy drug cis-platinum. Half maximal inhibitory concentration values for BPA-L1-Pt were 9.15 mu M on A549s and 16.61 mu M on HUVECs; the values for cis-platinum were 5.24 mu M on A549s and 23.14 mu M on HUVECs. Consequently, further synthesis studies should be performed to boost the cancer cell selectivity feature of BPA by varying metal and ligand types.
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    Investigation of Genotoxic Effects of Some Ruthenium Complexes According to Cis-platinum
    (2011-01-01T00:00:00Z) Alanyali, F. S.; Ergin, E.; Artagan, O.; Benkli, KADRİYE; BENKLİ, KADRIYE
    The aim of our study was, to synthesize and evaluate the mutagenicity of Ruthenium complexes, on Salmonella strains of TA100 and TA98 by Ames Test. [Ru(L)(2)(B)Pt] Cl-2 complexes were synthesized using 1, 10-phenanthroline-5,6-dione (dp) (L1), imidazo [4,5-f] [1,10] phenanthroline (ip) (L2) and 2-phenylimidazo [4,5-f] [1, 10] phenanthroline (pip) (L3) as ligands and bis-1,4-di [([1, 10] phenantrolin-5-il) amino]-2-buten (B) as a bridge molecule. The characterization of the intermediate and final compounds arising from this work will be carried out by means of a variety of spectroscopic methods, which include H-1 NMR, IR, MS and elemental analysis. The mutagenicity of [Ru (L)(2) (B) Pt] Cl-2 complexes, was investigated by the Ames Salmonella assay with strains TA 98 carrying a frameshift mutation and TA 100 base-pair substitution mutation were used in plate incorporation method in the absence of metabolic activation. RuL2BPt complex on TA98 Salmonella strain was found mutagenically effective at the dose of 100 mu g/plt. RuL3BPt complex gave mutagenic response on TA98 strain at doses of 25, 50, 100 mu g/plt, maximum mutagenic response was obtained at 25 mu g/plt dose. There was no significant increase of revertants due to the treatment with the doses of 5, 10, 25, 50 mu g/plt cis-platin on TA98. 100 mu g/plt dose showed mutagenic effect on TA98. On TA 100 strain dose related increase in the number of revertant colonies was observed but the number of revertants were not double the number of spontaneous colonies up to 100 mu g/plt dose. Only 100 mu g/pit dose showed mutagenic effect. The test compounds were directly effective, especially in the TA 98 Strain of Salmonella. Ruthenium derivatives was not mutagenic on the Salmonella strain of TA100.
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    The in vitro assessment of dipyridophenazine complexes in H-ras oncogene transformed rat embryo fibroblast 5RP7 cell line
    (2018-10-01) Kaplan, Ayse; Benkli, KADRİYE; Koparal, Ayse Tansu; BENKLİ, KADRIYE
    Purpose The aim of this study is to detect apoptotic and cytotoxic/antiproliferative effects of a ligand substance and its metal derivatives. The substances were investigated by using an h-ras oncogene transformed rat embryo fibroblast cell line (5RP7). Methods The cytotoxic influences of dipyrido[3,2-a:2,3-c]phenazine ligand, dipyrido[3,2-a:2,3-c] phenazine-platinum(II) complex ([Pt(dppz)Cl-2]) and dipyrido[3,2-a:2,3-c] phenazine-gold(III) complex ([Au(dppz)Cl-2]Cl) were determined with MTT (3[4,5-dimetiltiyazol2-yl]-2,5-difeniltetrazolyum bromid) assay on 5RP7 cells. Results Dipyrido[3,2-a:2,3-c] phenazine, dipyrido[3,2-a:2,3-c] phenazine-platinum(II) complex ([Pt(dppz)Cl-2]) and dipyrido[3,2-a:2,3-c] phenazine-gold(III) complexes ([Au(dppz)Cl-2]Cl) caused significant increase in cytotoxicity in a dose and time dependent manner. The effects of dipyridophenazine ligand (dppz) and its metal derivatives on apoptosis were monitorized using cytotoxic dose (10M) DAPI fluorescent staining. It was shown that dppz and its compounds induced apoptosis. Conclusions These findings show that dpzz and its complexes can be studied as novel alternative chemotherapeutics in cancer treatment.
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    Anti-lung Cancer and Anti-angiogenic Activities of New Designed Boronated Phenylalanine Metal Complexes
    (2018-01-01) Varol, Mehmet; Koparal, Ayse Tansu; Benkli, KADRİYE; Bostancioglu, Rakibe Beklem; BENKLİ, KADRIYE
    Background: Drug design and discovery studies still remain of great importance in the search for more convenient chemotherapeutic to avoid the drug resistance, systemic toxicity or the long-term side effects.