Person: TOK, FATİH
Loading...
Email Address
Birth Date
Research Projects
Organizational Units
Job Title
Last Name
TOK
First Name
FATİH
Name
13 results
Search Results
Now showing 1 - 10 of 13
Publication Metadata only Synthesis and biological evaluation of new pyrazolone Schiff bases as monoamine oxidase and cholinesterase inhibitors(ACADEMIC PRESS INC ELSEVIER SCIENCE, 2019) KAYMAKÇIOĞLU, BEDİA; Tok, Fatih; Kocyigit-Kaymakcioglu, Bedia; Saglik, Begum Nurpelin; Levent, Serkan; Ozkay, Yusuf; Kaplancikli, Zafer AsimIn the current work, Schiff base derivatives of antipyrine were synthesized. The chemical characterization of the compounds was confirmed using IR, H-1 NMR, C-13 NMR and mass spectroscopies. The inhibitory potency of synthesized compounds was investigated towards acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), and monoamine oxidases A and B (MAO-A and MAO-B) enzymes. Some of the compounds displayed significant inhibitory activity against AChE and MAO-B enzymes, respectively. According to AChE enzyme inhibition assay, compounds 3e and 3g were found as the most potent derivatives with IC50 values of 0.285 mu M and 0.057 mu M, respectively. Also, compounds 3a (IC50 = 0.114 mu M), 3h (IC50 = 0.049 mu M), and 3i (IC50 = 0.054 mu M) were the most active derivatives against MAO-B enzyme activity. So as to understand inhibition type, enzyme kinetics studies were carried out. Furthermore, molecular docking studies were performed to define and evaluate the interaction mechanism between compounds 3g and 3h and related enzymes. ADME (Absorption, Distribution, Metabolism, and Excretion) and BBB (Blood, Brain, Barier) permeability predictions were applied to estimate pharmacokinetic profiles of synthesized compounds.Publication Metadata only Design, synthesis, biological evaluation and molecular docking of novel molecules to PARP-1 enzyme(SCIENTIFIC TECHNICAL RESEARCH COUNCIL TURKEY-TUBITAK, 2019) KAYMAKÇIOĞLU, BEDİA; Tok, Fatih; Kocyigit-Kaumakcioglu, Bedia; Ilhan, Recep; Yilmaz, Sinem; Ballar-Kirmizibayrak, Petek; Taskim-Tok, TugbaPoly (ADP-ribose) polymerase (PARP) enzyme catalyzes the transfer of ADP-ribose into target proteins. Therefore, PARP is responsible for DNA repair, cell proliferation, and cell death. In this study, potential PARP enzyme inhibitors were designed and synthesized. The synthesized compounds were elucidated by Fourier-transform infrared spectroscopy, H-1 NMR, C-13 NMR, heteronuclear single-quantum correlation, and mass spectrometry, and their purity was checked via thin-layer chromatography, high-performance liquid chromatography, and elemental analysis. A total of 63 newly synthesized compounds were screened in terms of PARP inhibition by cellular PARylation assay in the HeLa cell line. It was found that 19 compounds significantly inhibited the H2O2-induced cellular PARylation. The chemosensitizer effect of these compounds in cancer cells treated with doxorubicin (doxo) was investigated. It was found that the combination of potent PARP inhibitors with doxo potentiated a cytotoxic effect, similar to that of olaparib. The results of the molecular docking and absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis revealed that compound 60 might be classified as a potential PARP inhibitor candidate. Taken together, all of the results suggested that carbohydrazide derivatives could be a promising lead for the treatment for cancer disorders.Publication Metadata only Pirazolon halkası taşıyan bazı Schiff bazlarının biyolojik etkilerinin incelenmesi(2018-11-16) TOK, FATİH; KAYMAKÇIOĞLU, BEDİA; UĞRAŞ Z., TOK F., KAYMAKÇIOĞLU B.Publication Metadata only Pirazolon halkasından hareketle sentezlenen çeşitli Schiff bazları üzerinde saflaştırmaçalışmaları(2018-11-16) TOK, FATİH; KAYMAKÇIOĞLU, BEDİA; Yılmaz S., TOK F., KAYMAKÇIOĞLU B.Publication Metadata only Synthesis, anticancer activity and ADMET studies of N-(5-methyl-1,3,4-thiadiazol-2-yl)-4-[(3-substituted)ureido/thioureido] benzenesulfonamide derivatives(TAYLOR & FRANCIS LTD, 2018) KAYMAKÇIOĞLU, BEDİA; Karakus, S.; Tok, F.; Tuerk, S.; Salva, E.; Tatar, G.; Taskin-Tok, T.; Kocyigit-Kaymakcioglu, B.A series of novel 4-[(3-substituted)ureido]-N-(5-methyl-1,3,4-thiadiazol-2-yl) benzenesulfonamides and 4-[(3-substituted)thioureido]-N-(5-methyl-1,3,4-thiadiazol-2-yl)benzenesulfonamides were prepared from 4-amino-N-(5-methyl-1,3,4-thiadiazol-2-yl)benzenesulfonamide (sulfamethizole). The structures of the synthesized compounds were determined by IR, H-1-NMR, MS and elemental analysis. The anticancer activity of these compounds was evaluated against human colorectal carcinoma (HCT116) and human cervix carcinoma (HeLa) cell lines. Compound 4 (4-{[(2,4-dichlorophenyl)carbamoyl]amino}-N-(5-methyl-1,3,4-thiadiazol-2-yl)benzenesulfonamide) showed marked anticancer activity, being the most active compounds in this series with the IC50 value of 13.92 +/- 0.22 mu M and 37.91 +/- 0.10 mu M against HeLa and HCT116, respectively. In silico, ADMET was used to examine their pharmacokinetic properties. ADMET (absorption, distribution, metabolism, excretion, and toxicity) studies were applied to develop new anticancer compound(s) with high selectivity. [GRAPHICS] .Publication Metadata only Synthesis and Anticancer Activity of New Hydrazide-hydrazoncs and Their Pd(II) Complexes(BENTHAM SCIENCE PUBL LTD, 2019) KAYMAKÇIOĞLU, BEDİA; Kocyigit-Kaymakcioglu, Bedia; Yazici, Senem Sinem; Tok, Fatih; Dikmen, Miris; Engur, Selin; Oruc-Emre, Emine Elcin; Iyidogan, AysegulBackground: Hydrazones, one of the important classes of organic molecules, are pharmaceutical agents comprising -CO-NH-N=CH- group in the structure therefore and exhibiting significant biological activity. Methods: 5-Chloro-N'-[(substituted)methylidene] pyrazine-2-carbohydrazide (3a-g) and their Pd(II) complexes (4a-h) were synthesized and investigated in vitro anticancer activity on A549, Caco2 cancer and normal 3T3 fibroblast cell lines, using the MTT assay. Results: Anticancer activity screening results revealed that some compounds showed remarkable cytotoxic effect. Among them, 5-chloro-N'-[(4-hydroxyphenyl)methylidene] pyrazine-2-carbohydrazide (3c) displayed higher cytotoxic activity against A549 cancer cell line than the reference drug cisplatin. Conclusion: Compound 3c showed high cytotoxic activity against A549 cancer cell line but it showed low cytotoxic effect against normal 3T3 fibroblast cell line. Antiproliferative and antimetastatic effects of 3c were determined by the real-time monitoring of cell proliferative system (RTCA DP). The cell proliferation, metastatic and invasive activities of A549 cells were decreased due to increased concentration of 3c.Publication Metadata only A new approach in cancer treatment: poly (ADP-ribose) polymerase-1 inhibitors(AVES PRESS LTD, 2015) KAYMAKÇIOĞLU, BEDİA; Tok, Fatih; Kocyigit-Kaymakcioglu, BediaInternal and external factors can damage DNA, the genetic material. Numerous repair mechanisms, which can repair those damages, exist in the normal cell. One of those is called PARP-1 enzyme. PARP-1 transfers ADP-ribose subunits from nicotinamide adenine nucleotide to protein acceptor. Thus, single strand DNA breaks can be repaired. If PARP-1 inhibition occurs, single strand DNA breaks cannot be repaired and double strand DNA breaks can be formed. Eventually, cells undergo necrosis or apoptosis. The aim of cancer treatment is to inhibit the PARP-1 enzyme. For this purpose, many studies have been published over the last decade and currently PARP-1 enzyme inhibitors which are in the phase studies and which are waiting to be marketed are available. In this review, information are given for the mechanisms by which DNA damage is repaired, the protection mechanism of the genomic integrity of PARP enzyme family and chemical structure of PARP-1 inhibitors which are improved to use in cancer treatment.Publication Open Access Antiproliferative activity of some tautomeric hydrazones derived from chalcones(MARMARA UNIV, FAC PHARMACY, 2016-02-02) KAYMAKÇIOĞLU, BEDİA; Tok, Fatih; Beyhan, Nagihan; Erzurumlu, Yalcin; Ilhan, Recep; Ballar, Petek; Kocyigit-Kaymakcioglu, BediaA new series of hydrazones synthesized from chalcones. Synthesized compounds have been characterized by IR, H-1-NMR and elemental analysis. Antiproliferative activity of compounds was investigated on Hela, A549, MCF7, HCC1937, MRC5 cells. All compounds exhibited cytotoxicity. Especially compounds 1b, 1c, 1f and 1i having 4-metylsulfonyl phenyl showed higher cytotoxicity against all of the cell lines compared to reference drug doxorubicin with low value of IC50=5,56-21,93 mu M. The most active compounds 1b, 1c, 1f and 1i were analyzed for their effect on autophagic processes. HCC1937 cells were treated with these compounds at IC50 concentration for 24 hours. An immunoblotting assay was performed to analysis autophagy markers and total polyubiquitinated protein levels. Compounds 1b, 1c, 1f and 1i significantly increased the conversion of LC3-I to LC3-II at IC50 concentration. None of the tested compounds changed the level of total polyubiquitinated proteins.Publication Metadata only SYNTHESIS AND BIOLOGICAL EVALUATION OF SOME NEW HYDRAZONE DERIVATIVES BEARING PYRIMIDINE RING AS ANALGESIC AND ANTI-INFLAMMATORY AGENTS(POLSKIE TOWARZYSTWO FARMACEUTYCZNE, 2018) KAYMAKÇIOĞLU, BEDİA; Akdag, Kadryiye; Unal, Gokhan; Tok, Fatih; Aricioglu, Feyza; Temel, Halide Edip; Kocyigit-Kaymakcioglu, BediaNew hydrazone derivatives were synthesized from 4-chloro-2-(methylthio) pyrimidine-5-carbohydrazide. IR, 1H-NMR, 13C-NMR, mass spectral data and elemental analysis characterized synthesized compounds. All compounds were investigated for analgesic and anti-inflammatory activity with hot plate test and biochemical assay, respectively. The results of anti-inflammatory activity showed that compound 2t had maximal lipoxygenase (LOX) inhibition (66.30%) whereas inhibitions of 2a, 2c, 2i, 2k, 2l, 2m, 2p, 2s, and 2u were observed between approximately 45-15%. Our results also indicated that 15 compounds of 21 had an analgesic effect in hot plate test. Analgesic effect of 2l, 2s, 2t began earlier than others while the effect of 2i began at the latest time. According to the activity results, compound 2t have both significant analgesic and anti-inflammatory effects.Publication Open Access Synthesis and structure-activity relationships of carbohydrazides and 1,3,4-oxadiazole derivatives bearing an imidazolidine moiety against the yellow fever and dengue vector, Aedes aegypti(JOHN WILEY & SONS LTD, 2018-02) KAYMAKÇIOĞLU, BEDİA; Tok, Fatih; Kocyigit-Kaymakcioglu, Bedia; Tabanca, Nurhayat; Estep, Alden S.; Gross, Aaron D.; Geldenhuys, Werner J.; Becnel, James J.; Bloomquist, Jeffrey R.BACKGROUND 1,3,4-Oxadiazole and imidazolidine rings are important heterocyclic compounds exhibiting a variety of biological activities. In this study, novel compounds with oxadiazole and imidazolidine rings were synthesized from 3-(methylsulfonyl)-2-oxoimidazolidine-1-carbonyl chloride and screened for insecticidal activities. The proposed structures of the 17 synthesized compounds were confirmed using elemental analysis, infrared (IR), proton nuclear magnetic resonance (H-1-NMR), and mass spectroscopy. RESULTS None of the compounds showed larvicidal activity at the tested concentrations against first-instar Aedes aegypti larvae. However, nine compounds exhibited promising adulticidal activity, with mortality rates of >= 80% at 5 mu g per mosquito. Further dose-response bioassays were undertaken to determine median lethal dose (LD50) values. Compounds 1, 2b, 2c, 2d, 2 g, 3b, 3c, 3 g, and 3 h were effective, with typical LD50 values of about 5 - 10 mu g per mosquito against female Ae. aegypti. Compounds 2c (bearing a nitro group on the aromatic ring; LD50 = 2.80 0.54 mu g per mosquito) and 3 h (double halogen groups at 2,4 position on the phenyl ring; LD50 = 2.80 +/- 0.54 mu g per mosquito) were the most promising compounds. CONCLUSION Preliminary mode of action studies failed to show consistent evidence of either neurotoxic or mitochondria-directed effects. Further chemical synthesis within this series may lead to the development of new effective insecticides. (C) 2017 Society of Chemical Industry