Person: ERDEM, SAFİYE
Loading...
Email Address
Birth Date
Research Projects
Organizational Units
Job Title
Last Name
ERDEM
First Name
SAFİYE
Name
39 results
Search Results
Now showing 1 - 10 of 39
Publication Metadata only Design and Synthesis of Pyrrolotriazepine Derivatives: An Experimental and Computational Study(AMER CHEMICAL SOC, 2013) ERDEM, SAFİYE; Menges, Nurettin; Sari, Ozlem; Abdullayev, Yusif; Erdem, Safiye Sag; Balci, MetinThe pyrrole derivatives having carbonyl groups at the C-2 position were converted to N-propargyl pyrroles. The reaction of those compounds with hydrazine monohydrate resulted in the formation of 5H-pyrrolo[2,1-d][1,2,5]-triazepine derivatives. The synthesis of these compounds was accomplished in three steps starting from pyrrole. On the other hand, attempted cyclization of a pyrrole ester substituted with a propargyl group at the nitrogen atom gave, unexpectedly, the six-membered cyclization product, 2-amino-3-methylpyrrolo[1,2-a]pyrazin-1(2H)-one as the major product. The expected cyclization product with a seven-membered ring, 4-methyl-2,3-dihydro-1H-pyrrolo[2,1-d][1,2,5]-triazepin-1-one was formed as the minor product and was converted quantitatively to the major product. The formation mechanism of the products was investigated, and the results obtained were also supported by theoretical calculations.Publication Metadata only Computational insight into the phthalocyanine-DNA binding via docking and molecular dynamics simulations(ELSEVIER SCI LTD, 2018) MUTLU, ÖZAL; Ozalp, Lalehan; Erdem, Safiye Sag; Yuce-Dursun, Basak; Mutlu, Ozal; Ozbil, MehmetPhthalocyanines are considered as good DNA binders, which makes them promising anti-tumor drug leads. The purpose of this study is to investigate the interactions between DNA and quaternary metallophthalocyanine derivatives (Q-MPc) possessing varying metals (M = Zn, Ni, Cu, Fe, Mg and Ca) by molecular docking since there seems to be a lack of information in the literature regarding this issue. In this direction, Autodock Vina and Molegro Virtual Docker programs were employed. Autodock Vina results reveal that each Q-MPc derivative binds to DNA strongly with similar binding energies and almost identical binding modes. They bind to the grooves of DNA by constituting favorable interactions between phosphate groups of DNA and Q-MPcs. Although changing the metal has no significant effect on binding, presence of quaternary amine substituents increases the binding constant K-b by about 2-fold comparing to the core Pc (ZnPc). Contrary to Autodock Vina, the calculated Molegro Virtual Docker binding scores have been more diverse indicating that the scoring function of Molegro is better in differentiating these metals. Despite the fact that Molegro is superior to Autodock Vina in terms of metal characterization, Autodock Vina and Molegro exhibit similar binding sites for the studied metallophthalocyanines. We propose that Q-MPc derivatives designed in this study are promising anti-tumor lead compounds since they tightly bind to DNA with considerably high K-b values. Cationic substituents and presence of metal have both positive effects on DNA binding which is critical for designing DNA-active drugs. Additional calculations employing molecular dynamics (MD) simulations verified the stability of Q-MPc-DNA complexes which remained in contact after 20 ns via attractive interactions mainly between DNA backbone and the Pc metal center.Publication Metadata only Synthesis of hydrazine containing piperazine or benzimidazole derivatives and their potential as a-amylase inhibitors by molecular docking, inhibition kinetics and in vitro cytotoxicity activity studies(SPRINGER BIRKHAUSER, 2021) ERDEM, SAFİYE; Cakmak, Ummuhan; Oz-Tuncay, Fulya; Basoglu-Ozdemir, Serap; Ayazoglu-Demir, Elif; Demir, Ilke; Colak, Ahmet; Celik-Uzuner, Selcen; Erdem, Safiye Sag; Yildirim, NuriThe alpha-amylase is the main product of pancreas and is necessarily involved in the hydrolysis of carbohydrates into glucose so that it has been known to be a pioneer target for type 2 Diabetes mellitus (DM). Type 2 DM has no certain cure and the global increase in the cases of DM requires effective and extensive number of drug candidates. Drug discovery studies using organic biochemistry approaches are of important to describe novel compounds. This study aimed to reveal inhibitory potential of 13 novel compounds containing piperazine or benzimidazole moieties on alpha-amylase. The novel compounds were synthesized, structurally corroborated by various spectral analysis (FTIR, UV-Vis, H-1 NMR and C-13 NMR) and screened for anti alpha-amylase activity. Among the synthesized derivatives, compound 14 was found to be the most potent inhibitor of alpha-amylase having IC50 64.8 +/- 1.8 mu M. Inhibition types and K-i values of the most effective molecules (14 and 10a with different moieties) were further investigated. Molecular docking studies were conducted to correlate the outcome of in vitro biochemical kinetic assays and therefore rationalize the binding interactions. In vitro cytotoxicity studies on pancreatic cancer (AR42J) cells were then performed for compound14, and the compound was found to be more effective compared to the positive control, acarbose. Prediction of in silico ADME properties of all tested molecules were determined.Publication Metadata only A DFT Study on the Mechanism of the Annulation Reaction of Trichloronitroethylene with Aniline in the Synthesis of Quinoxalinone-N-oxides(AMER CHEMICAL SOC, 2009) ERDEM, SAFİYE; Ozpinar, Gul A.; Erdem, Safiye S.; Meyer, Christian; Kaufmann, Dieter E.The new annulation reaction of trichloronitroethylene with aniline results in the formation of a quinoxalinone-N-oxide derivative. The mechanism of this one-pot annulation reaction between trichloronitroethylene (TCNiE) and anilines has been extensively investigated with B3LYP/6-31+G** methodology. Five different paths (1-5) were proposed and modeled by using this method. These paths were compared in terms of the activation energies of their rate-determining steps and in regard to the experimental findings. Paths 3 and 5, proceeding via four-membered heterocyclic rings, were found to be the most plausible paths with activation energies of 32 and 29 kcal/mol for the rate-determining steps, respectively. The effects of substituent, solvent, temperature, and computational method on these steps were also investigated. The results showed that path 5 is the most plausible mechanism for the annulation reaction of trichloronitroethylene with aniline.Publication Metadata only Insights into the binding mode of new N-substituted pyrazoline derivatives to MAO-A: docking and quantum chemical calculations(SPRINGER WIEN, 2013) ERDEM, SAFİYE; Erdem, Safiye Sag; Turkkan, Seyhan; Yelekci, Kemal; Gokhan-Kelekci, NesrinThe binding modes of four N-substituted pyrazoline derivatives as novel MAO-A inhibitory agents were investigated using docking and quantum chemical molecular modelling tools.Publication Metadata only Newly synthesized piperazine derivatives as tyrosinase inhibitors: in vitro and in silico studies(Springer Science and Business Media Deutschland GmbH, 2022) ERDEM, SAFİYE; Dokuzparmak C., Oz Tuncay F., Basoglu Ozdemir S., Kurnaz B., Demir I., Colak A., Sag Erdem S., Yildirim N.In this study, a series of new organic compounds with piperazine as a fundamental skeleton was synthesized and evaluated for their tyrosinase inhibitory potentials by in vitro and in silico studies. The in vitro studies have shown that compounds 10a and 10b bearing 1,2,4, triazole nucleus could be considered potent tyrosinase inhibitors with IC50 values of 31.2 ± 0.7 and 30.7 ± 0.2 µM, respectively. 10b (Ki = 9.54 µM, mixed type inhibition) with the lowest IC50 value among derivatives was selected to determine kinetic constants and inhibition types. Furthermore, molecular docking analysis was performed for all compounds and it was observed that 4b, 5a, 4c, and 10b showed promising inhibitory effect on tyrosinase activity. Based on docking results, ADME predictions and in vitro studies, 10b might be considered suitable oral drug candidates for further studies. © 2022, Iranian Chemical Society.Publication Metadata only A computational study on heterodimerization of charged porphyrins(JOHN WILEY & SONS LTD, 2001) ERDEM, SAFİYE; Erdem, SSThe structures of the charged porphyrins and their dimers have been investigated with computational methods. Dimers have been formed based on electrostatic attraction of the opposite charges on two different porphyrin monomers, tetra ammonium porphyrin (TAP) and tetra carboxy porphyrin (TCP). Semi-empirical quantum mechanical calculations have been employed to explore the most stable ground-state structures of TCP, TAP and their hetero-dimers. Dimeric structures analyzed are all in face-to-face fashion indicating the strong electrostatic attraction between the two porphyrin rings. Calculations have also predicted that the protons transfer from -NH3+; groups to -COO- groups when the interplanar separation is shorter than 3.7 Angstrom. Copyright (C) 2001 John Wiley & Sons, Ltd.Publication Metadata only QSPR analysis of the toxicity of aromatic compounds to the algae (Scenedesmus obliquus)(PERGAMON-ELSEVIER SCIENCE LTD, 2007) ERDEM, SAFİYE; Sacan, Melek Turker; Ozkul, Mustafa; Erdem, Safiye SagThe quantitative structure-property relationship (QSPR) model was developed for the 50% effective inhibition concentration (48 h - EC50) of 36 selected substituted benzenes for the algae Scenedesmus obliquus by the application of the Characteristic Root Index (CRI) model. To increase the predictive power of the CRI-based model, the following semi-empirical molecular descriptors calculated by the quantum chemical PM3 method were included: the energy of the highest occupied molecular orbital (E-HOMO), the energy of the lowest unoccupied molecular orbital (E-LUMO), and the dipole moment (mu). A two-descriptor model with a correlation coefficient of r = 0.926 was developed without the outliers from multiple regression analysis [-log EC50 = 0.494 (+/- 0.072) CRI - 0.798 (+/- 0.063) E-LUMO + 1.985 (+/- 0.169)]. E-LUMO was the most important parameter, followed by the CRI. E-LUMO reflects electronic properties, whereas the CRI reflects hydrophobicity, molecular size, and branching. The statistical robustness of the developed model was validated by the modified jackknife test. The predictive accuracy of the proposed model was compared with the recently published study in which a toxicity model was developed for the same algae. Because of its high statistical significance, the validated model has been used to predict -log EC50 values of compounds for which there are no experimental measurements. (C) 2007 Elsevier Ltd. All rights reserved.Publication Metadata only İnsan monoamin oksidaz a ve b inhibitörleri olarak benzokumarin türevlerinin sentezi ve biyolojik olarak değerlendirilmesi(2015-05-07) DANIŞ, ÖZKAN; DEMİR, SERAP; OGAN, AYŞE; ERDEM, SAFİYE; Danış Ö., Yüce Dursun B., Demir S., Alparslan M., Ogan A., Erdem S.Publication Metadata only Synthesis of Tolmetin Hydrazide-Hydrazones and Discovery of a Potent Apoptosis Inducer in Colon Cancer Cells(WILEY-V C H VERLAG GMBH, 2015) ÖZSAVCI, DERYA; Kucukguzel, S. Guniz; Koc, Derya; Cikla-Suzgun, Pelin; Ozsavci, Derya; Bingol-Ozakpinar, Ozlem; Mega-Tiber, Pinar; Orun, Oya; Erzincan, Pinar; Sag-Erdem, Safiye; Sahin, FikrettinTolmetin hydrazide and a novel series of tolmetin hydrazide-hydrazones 4a-l were synthesized in this study. The structures of the new compounds were determined by spectral (FT-IR, H-1 NMR) methods. N-[(2,6-Dichlorophenyl)methylidene]-2-[1-methyl-5-(4-methylbenzoyl)-1H-pyrrol-2-yl]acetohydrazide (4g) was evaluated in vitro using the MTT colorimetric method against the colon cancer cell lines HCT-116 (ATCC, CCL-247) and HT-29 (ATCC, HTB-38) to determine growth inhibition and cell viability at different doses. Compound 4g exhibited anti-cancer activity with an IC50 value of 76M against colon cancer line HT-29 (ATCC, HTB-38) and did not display cytotoxicity toward control NIH3T3 mouse embryonic fibroblast cells compared to tolmetin. In addition, this compound was evaluated for caspase-3, caspase-8, caspase-9, and annexin-V activation in the apoptotic pathway, which plays a key role in the treatment of cancer. We demonstrated that the anti-cancer activity of this compound was due to the activation of caspase-8 and caspase-9 involved in the apoptotic pathway. In addition, in this study, we investigated the catalytical effect of COX on the HT-29 cancer line, the apoptotic mechanism, and the moleculer binding of tolmetin and compound 4g on the COX enzyme active site.