Yazar "Celik, Ayhan" seçeneğine göre listele

Listeleniyor 1 - 7 / 7
  • [ X ]
    Öğe
    Antiproliferative activity of Humulus lupulus extracts on human hepatoma (Hep3B), colon (HT-29) cancer cells and proteases, tyrosinase, ?-lactamase enzyme inhibition studies
    (Taylor & Francis Ltd, 2016) Onder, Ferah Comert; Ay, Mehmet; Turkoglu, Sumeyye Aydogan; Kockar, Feray Tura; Celik, Ayhan
    The aims of this study were to examine the antiproliferation of Humulus lupulus extracts on human hepatoma carcinoma (Hep3B) and human colon carcinoma (HT-29) cell lines along with enzyme inhibitory effects of the crude extracts. Potential cell cytotoxicity of six different H. lupulus extracts were assayed on various cancer cells using MTT assay at 24, 48 and 72h intervals. Methanol-1 extract has inhibited the cell proliferation with doses of 0.6-1mg/mL in a time dependent (48 and 72 hours) manner in Hep3B cells with 70% inhibition, while inhibitory effect was not seen in colon cancer cells. Acetone extract has increased the cell proliferation at low doses of 0.1mg/mL for 72h in Hep3B cells and 0.1-0.2mg/mL for 48 and 72h in HT29 cells. The inhibitory effects of the extracts were compared by relative maximum activity values (V-max) using proteases such as -chymotrypsin, trypsin and papain, tyrosinase and -lactamase (penicillinase).
  • [ X ]
    Öğe
    Biological evaluation and molecular docking. studies of nitro benzamide derivatives with respect to in vitro anti-inflammatory activity
    (Elsevier, 2017) Turner, Tugba B.; Onder, Ferah Comert; Ipek, Hande; Gungor, Tugba; Savranoglu, Seda; Tok, Tugba Taskin; Celik, Ayhan
    A series of nitro substituted benzamide derivatives were synthesized and evaluated for their potential anti-inflammatory activities in vitro. Firstly, all compounds (1-6) were screened for their inhibitory capacity on LPS induced nitric oxide (NO) production in RAW264.7 macrophages. Compounds 5 and 6 demonstrated significantly high inhibition capacities in a dose-dependent manner with IC50 values of 3.7 and 53 mu M, respectively. These two compounds were also accompanied by no cytotoxicity at the studied concentrations (max 50 mu M) in macrophages. Molecular docking analysis on iNOS revealed that compounds 5 and 6 bind to the enzyme more efficiently compared to other compounds due to having optimum number of nitro groups, orientations and polarizabilities. In addition, 5 and 6 demonstrated distinct regulatory mechanisms for the expression of the iNOS enzyme at the mRNA and protein levels. Specifically, both suppressed expressions of COX-2, IL-1 beta and TNF-alpha significantly, at 10 and 20 mu M. However, only compound 6 significantly and considerably decreased LPS-induced secretion of IL-1 beta and TNF-alpha. These results suggest that compound 6 may be a multi-potent promising lead compound for further optimization in structure and as well as for in vivo validation studies. (C) 2016 Published by Elsevier B.V.
  • [ X ]
    Öğe
    Modification of existing antibiotics in the form of precursor prodrugs that can be subsequently activated by nitroreductases of the target pathogen
    (Pergamon-Elsevier Science Ltd, 2016) Celik, Ayhan; Yetis, Gulden; Ay, Mehmet; Gungor, Tugba
    The use of existing antibiotics in the form of prodrug followed by activation using enzymes of pathogenic origin could be a useful approach for antimicrobial therapy. To investigate this idea, a common antibiotic, sulfamethoxazole has been redesigned in the form of a prodrug by simple functional group replacement. Upon reductive activation by a type I nitroreductase from a pathogen, the drug displayed enhanced antimicrobial capacity. This strategy could improve the efficacy and selectively of antibiotics and reduce the incidence of resistance. (C) 2016 Elsevier Ltd. All rights reserved.
  • [ X ]
    Öğe
    Prodrugs for Nitroreductase Based Cancer Therapy-1: Metabolite Profile, Cell Cytotoxicity and Molecular Modeling Interactions of Nitro Benzamides with Ssap-NtrB
    (Bentham Science Publ Ltd, 2018) Gungor, Tugba; Yetis, Gulden; Onder, Ferah C.; Tokay, Esra; Tok, Tugba T.; Celik, Ayhan; Ay, Mehmet
    Background: Directed Enzyme Prodrug Therapy (DEPT) as an alternative method against conventional cancer treatments, in which the non-toxic prodrug is converted to highly cytotoxic derivative, has attracted an ample attentions in recent years for cancer therapy studies. Objective: The metabolite profile, cell cytotoxicity and molecular modeling interactions of a series of nitro benzamides with Ssap-NtrB were investigated in this study. Method: A series of nitro-substituted benzamide prodrugs (1-4) were synthesized and firstly investigated their enzymatic reduction by Ssap-NtrB (S. saprophyticus Nitroreductase B) using HPLC analysis. Resulting metabolites were analyzed by LC-MS/MS. Molecular docking studies were performed with the aim of the investigating the relationship between nitro benzamide structures (prodrugs 1-4) and Ssap-NtrB at molecular level. Cell viability assay on two cancer cell lines, hepatoma (Hep3B) and colon (HT-29) cancer models and healthy cell model HUVEC. Upon the reduction of benzamide prodrugs by Ssap-NtrB, the corresponding amine effectors were tested in a cell line panel comprising PC-3, Hep3B and HUVEC cells and were compared with the established NTR substrates, CB1954 (an aziridinyl dinitrobenzamide). Results: Cell viability assay resulted in while prodrugs 1, 2 and 3 had no remarkable cytotoxic effects, prodrug 4 showed the differential effect, showing moderate cytotoxicity with Hep3B and HUVEC. The metabolites that obtained from the reduction of nitro benzamide prodrugs (1-4) by Ssap-NtrB, showed differential cytotoxic effects, with none toxic for HUVEC cells, moderate toxic for Hep3B cells, but highly toxic for PC3 cells. Conclusion: Amongst all metabolites of prodrugs after Ssap-NtrB reduction, N-(2,4-dinitrophenyl)-4-nitrobenzamide (3) was efficient and toxic in PC3 cells as comparable as CB1954. Kinetic parameters, molecular docking and HPLC results also confirm that prodrug 3 is better for Ssap-NtrB than 1, 2 and 4 or known cancer prodrugs of CB1954 and SN23862, demonstrating that prodrug 3 is an efficient candidate for NTR based cancer therapy
  • [ X ]
    Öğe
    PRODRUGS FOR NITROREDUCTASE BASED CANCER THERAPY-2: Novel amide/Ntr combinations targeting PC3 cancer cells
    (Elsevier France-Editions Scientifiques Medicales Elsevier, 2019) Gungor, Tugba; Onder, Ferah Comert; Tokay, Esra; Gulhan, Unzile Guven; Hacioglu, Nelin; Tok, Tugba Taskin; Celik, Ayhan
    The use of nitroreductases (NTR) that catalyze the reduction of nitro compounds by using NAD(P)H in GDEPT (Gene-directed enzyme prodrug therapy) studies which minimize toxicity at healthy cells and increases concentration of drugs at cancer cells is remarkable. Discovery of new prodrugiNTR combinations is necessary to be an alternative to known prodrug candidates such as CB1954, SN23862, PR 104A. For this aim, nitro containing aromatic amides (A1-A23)(2) were designed, synthesized, performed in silico ADMET and molecular docking techniques in this study. Prodrug candidates were studied on reduction potentials with Ssap-NtrB by HPLC system. Also, cyototoxic properties and prodrug ability of these amides were investigated using different cancer cell lines such as Hep3B and PC3. As a result of theoretical and biological studies, combinations of A5, A6 and A20 with Ssap-NtrB can be suggested as potential prodrugs/enzyme combinations at NTR based cancer therapy compared with CB1954/NfsB. (C) 2019 Elsevier Masson SAS. All rights reserved.
  • [ X ]
    Öğe
    Prodrugs for nitroreductase based cancer therapy-4: Towards prostate cancer targeting: Synthesis of N-heterocyclic nitro prodrugs, Ssap-NtrB enzymatic activation and anticancer evaluation
    (Academic Press Inc Elsevier Science, 2020) Gungor, Tugba; Tokay, Esra; Gulhan, Unzile Guven; Hacioglu, Nelin; Celik, Ayhan; Kockar, Feray; Ay, Mehmet
    In this study, various N-heterocyclic nitro prodrugs (NHN1-16) containing pyrimidine, triazine and piperazine rings were designed and synthesized. The final compounds were identified using FT-IR, H-1 NMR, C-13 NMR as well as elemental analyses. Enzymatic activities of compounds were conducted by using HPLC analysis to investigate the interaction of substrates with Ssap-NtrB nitroreductase enzyme. MTT assay was performed to evaluate the toxic effect of compounds against Hep3B and PC3 cancer cell lines and healthy HUVEC cell. It was observed that synthesized compounds NHN1-16 exhibited different cytotoxic profiles. Pyrimidine derivative NHN3 and triazine derivative NHN5 can be good drug candidates for prostate cancer with IC50 values of 54.75 mu M and 48.9 mu M, respectively. Compounds NHN6, NHN10, NHN12, NHN14 and NHN16 were selected as prodrug candidates because of non-toxic properties against three different cell models. The NHN prodrugs and Ssap-NtrB combinations were applied to SRB assay to reveal the prodrug capabilities of these selected compounds. SRB screening results showed that the metabolites of all selected non-toxic compounds showed remarkable cytotoxicity with IC50 values in the range of 1.71-4.72 nM on prostate cancer. Among the tested compounds, especially piperazine derivatives NHN12 and NHN14 showed significant toxic effect with IC50 values of 1.75 nM and 1.79 nM against PC3 cell compared with standart prodrug CB1954 (IC50: 1.71 nM). Novel compounds NHN12 and NHN14 can be considered as promising prodrug candidates for nitroreductase-prodrug based prostate cancer therapy.
  • [ X ]
    Öğe
    Prodrugs for nitroreductase-based cancer therapy-3: Antitumor activity of the novel dinitroaniline prodrugs/Ssap-NtrB enzyme suicide gene system: Synthesis, in vitro and in silico evaluation in prostate cancer
    (Elsevier France-Editions Scientifiques Medicales Elsevier, 2020) Tokay, Esra; Gungor, Tugba; Hacioglu, Nelin; Onder, Ferah Cornett; Gullhan, Unzile Guven; Tok, Tugba Taskin; Celik, Ayhan
    Prodrugs for targeted tumor therapies have been extensively studied in recent years due to not only maximising therapeutic effects on tumor cells but also reducing or eliminating serious side effects on healthy cells. This strategy uses prodrugs which are safe for normal cells and form toxic metabolites (drugs) after selective reduction by enzymes in tumor tissues. In this study, prodrug candidates (1-36) containing nitro were designed, synthesized and characterized within the scope of chemical experiments. Drug-likeness properties of prodrug candidates were analyzed using DS 2018 to investigate undesired toxicity effects. In vitro cytotoxic effects of prodrug canditates were performed with MTT assay for human hepatoma cells (Hep3B) and prostate cancer cells (PC3) and human umbilical vein endothelial cells (HUVEC) as healthy control. Non-toxic compounds (3, 5, 7,10, 12, 15,17, 19 and 21-23), and also compounds (1, 2, 5, 6, 9, 11, 14, 16, 20 and 24) which had low toxic effects, were selected to examine their suitability as prodrug canditates. The reduction profiles and kinetic studies of prodrug/Ssap-NtrB combinations were performed with biochemical analyses. Then, selected prodrug/Ssap-NtrB combinations were applied to prostate cancer cells to determine toxicity. The results of theoretical, in vitro cytotoxic and biochemical studies suggest 14/Ssap-NtrB, 22/Ssap-NtrB and 24/Ssap-NtrB may be potential prodrug/enzyme combinations for nitroreductase (Ntr)-based prostate cancer therapy. (C) 2019 Elsevier Masson SAS. All rights reserved.