Person: ERDEM, SAFİYE
Loading...
Email Address
Birth Date
Research Projects
Organizational Units
Job Title
Last Name
ERDEM
First Name
SAFİYE
Name
48 results
Search Results
Now showing 1 - 10 of 48
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 Open Access Stable hemiaminals from axially chiral pyridine compounds(2023-01-01) ERDEM, SAFİYE; Tuncel S. T., Demir I., ERDEM S., Dogan I.© 2023 Wiley Periodicals LLC.In this study, we have synthesized a series of 3-(pyridin-2-yl)-2-(pyridin-2-ylimino)thiazolidin-4-ol derivatives regioselectively from 2-iminothiazolidin-4-ones using LiAlH4 at room temperature. Due to the presence of the restricted rotation around the N3-Caryl single bond, the formation of M/P isomers was observed. The OH group of the hemiaminal was found to orient itself on the same side with pyridyl nitrogen during this restricted rotation to form an intramolecular hydrogen bond, which was demonstrated by the computational DFT study. This orientation presumably inhibited the occurrence of dehydration and stabilized the molecule.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 Open Access In vitro and in silico investigation of inhibitory activities of 3-arylcoumarins and 3-phenylazo-4-hydroxycoumarin on MAO isoenzymes(2022-11-01) DANIŞ, ÖZKAN; DEMİR, SERAP; ERDEM, SAFİYE; OGAN, AYŞE; Yuce-Dursun B., DANIŞ Ö., Ozalp L., Sahin E., DEMİR S., ERDEM S., OGAN A.A series of 3-aryl coumarin derivatives and 3-phenylazo-4-hydroxycoumarin were evaluated for their monoamine oxidase (MAO) A and B inhibitory activity and selectivity by fluorometric enzymological assays. Among 21 coumarin derivatives, compound 21 (3-phenylazo-4-hydroxycoumarin) displayed a good inhibitory activity (0.12 +/- 0.02 mu M) and very high selectivity for MAO-B (SI > 833.33). The inhibition was determined as mixed-type and not time-dependent. Docking studies, molecular dynamics and molecular mechanics/Poisson-Boltzmann surface area (MM/PBSA) calculations were performed to elucidate in vitro results. Our results reveal that the insertion of an azo linker between coumarin and phenyl rings in 3-arylcoumarins enhances MAO-B selectivity enormously since such a linker leads to the perfect alignment of the coumarin ring in the aromatic cage and the phenyl ring in the entrance cavity of MAO-B active site. Hydrogen bond interactions with Cys172 in the active site entrance of MAO-B also contributes to the remarkably higher inhibitory activity and selectivity for MAO-B.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 Open Access How fullerene derivatives (FDs) act on therapeutically important targets associated with diabetic diseases(2022-01-01) ERDEM, SAFİYE; Fjodorova N., Novic M., Venko K., Drgan V., Rasulev B., SAÇAN M., ERDEM S., Tugcu G., Toropova A. P., Toropov A. A.Fullerene derivatives (FDs) belong to a relatively new family of nano-sized organic compounds. They are widely applied in materials science, pharmaceutical industry, and (bio) medicine. This research focused on the study of FDs in terms of their potential inhibitory effect on therapeutic targets associated with diabetic disease, as well as analysis of protein-ligand binding in order to identify the key binding characteristics of FDs. Therapeutic drug compounds when entering the biological system usually inevitably encounter and interact with a vast variety of biomolecules that are responsible for many different functions in organisms. Protein biomolecules are the most important functional components and used in this study as target structures. The structures of proteins [(PDB ID: 1BMQ, 1FM6, 1GPB, 1H5U, 1US0)] belonging to the class of anti-diabetes targets were obtained from the Protein Data Bank (PDB). Protein binding activity data (binding scores) were calculated for the dataset of 169 FDs related to these five proteins. Subsequently, the resulting data were analyzed using various machine learning and cheminformatics methods, including artificial neural network algorithms for variable selection and property prediction. The Quantitative Structure-Activity Relationship (QSAR) models for prediction of binding scores activity were built up according to five Organization for Economic Co-operation and Development (OECD) principles. All the data obtained can provide important information for further potential use of FDs with different functional groups as promising medical antidiabetic agents. Binding scores activity can be used for ranking of FDs in terms of their inhibitory activity (pharmacological properties) and potential toxicity. (c) 2022 The Authors. Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology. This is an open access article under the CC BY license (http://creativecommons. org/licenses/by/4.0/).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.