Scopus İndeksli Yayınlar Koleksiyonu
Permanent URI for this collectionhttps://hdl.handle.net/20.500.12573/395
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Article Toward the Design of New Α-Carboline Derivatives Against Anaplastic Lymphoma Kinase (Alk): A Comprehensive in Silico Approach(Wiley-VCH Verlag GmbH, 2025-11) Sari, Ceyhun; Akcok, IsmailAfter the first description of anaplastic lymphoma kinase (ALK) in an anaplastic large cell lymphoma cell line as a nucleophosmin (NPM) fusion partner, ALK and its various fusion partners have been implicated in numerous cancers such as non-small cell lung cancer (NSCLC), anaplastic large cell lymphoma (ALCL), neuroblastoma, and rhabdomyosarcoma. In the last decade, several compounds targeting ALK have been developed and approved by the Food and Drug Administration (FDA). Despite the advances of generations of ALK inhibitors, a recent study highlighted that around half of the ALK-positive NSCLC patients will go through disease progression in response to first-line alectinib, which is a second-generation ALK inhibitor. In this study, we aimed to propose a novel alpha-carboline compound targeting the ALK tyrosine kinase domain to be used against various types of cancer in which ALK fusion proteins may be involved. In this regard, we designed more than 200 alpha-carboline derivatives and investigated their binding properties against ALK tyrosine kinase by using in silico protocols consisting of molecular docking studies, molecular dynamics simulations, MM/PBSA binding free energy calculation, and essential dynamics analysis. Considering the obtained results, we developed two promising candidates, compounds 208 & 209 with -9.05 and -9.80 binding energies, respectively, which demonstrated improved binding profiles over the course of a 300 ns simulation.Article Citation - WoS: 6Citation - Scopus: 7Therapeutic Potential of Nitrogen-Substituted Oleanolic Acid Derivatives in Neuroinflammatory and Cytokine Pathways: Insights From Cell-Based and Computational Models(Wiley-VCH Verlag GmbH, 2025-04-22) Turgut, Gurbet Celik; Pepe, Nihan Aktas; Ekiz, Yagmur Ceylan; Senol, Halil; Sen, AlaattinThis study was conducted to investigate the mechanism of the potential and anti-inflammatory properties of nitrogen-substituted oleanolic acid derivatives that can be used to treat neuroinflammatory diseases. Nitrogen-containing oleanolic acid derivatives have been evaluated for their anti-neuroinflammatory effects in vitro in neuronal and monocytic cell lines at nontoxic doses, and the production of cytokines (TNF-alpha, IL-6 and IL-17), the inflammatory enzyme induced nitric oxide synthase (iNOS) and NF-kappa B signalling under LPS-stimulated conditions, and the expression of genes associated with Alzheimer's disease have been assessed. In addition, molecular docking and molecular dynamics simulation assessments are conducted in silico. Key protein markers of neurodegenerative diseases, especially Alzheimer's disease and neuroinflammation, TAU protein levels, and microglial activation, as well as ionised calcium-binding adaptor protein-1 (IBA1) levels, were significantly reduced with the addition of oleanolic acid derivatives. LPS-induced NF-kappa B luciferase reporter activity and iNOS activity were significantly inhibited, approaching the levels in uninduced controls. The mRNA expression of proinflammatory cytokines critical for neuroinflammation, such as TNF-alpha, NF-kappa B, IL-6 and IL-17, was reduced twofold to sevenfold. Furthermore, the molecular docking and MD simulation analyses revealed potential interactions with the TNF-alpha and NF-kappa B proteins. These findings underscore the potential of oleanolic acid derivatives, particularly compound 16, as candidates for further development as therapeutic agents for neurodegenerative diseases associated with chronic inflammation.Article Citation - WoS: 3Citation - Scopus: 3Superior CdSe/ZnS@Fe2O3 Yolk-Shell Nanoparticles as Optically Active MRI Contrast Agents(Wiley-VCH Verlag GmbH, 2022-07) Ekici, Derya D.; Mutlugun, EvrenWe have developed a robust synthesis methodology for quantum dots (QDs) nanoparticles with magnetic properties designed for biomodal imaging. These nanocrsytlas consists of a semiconductor quantum dot core with engineered fluorescence, which is located in a paramagnetic iron oxide shell that acts as a magnetic resonance imaging (MRI) contrast agent. Yolk-shell CdSe/ZnS@Fe2O3 nanoparticles (NPs) are synthesized via sonochemical decomposition of iron pentacarbonyl (Fe(CO)(5)) using the oleylamine (OAm) as the ligand. The sonochemical synthesis method of magnetic fluorescent NPs that can be used as MRI contrast agents provided advantages such as improved quantum efficiency and homogeneous size distributions. It has been determined that the luminescence efficiency of quantum dots decreases in coatings that can be made at high temperatures by thermal decomposition. In order to eliminate the disadvantage of elevated temperatures, the sonochemical decomposition method, which allows coating at low temperatures, has been used. With this method, yolk-shell (CdSe/ZnS@Fe2O3) nanoparticles were produced with high photoluminescence quantum efficiency and homogeneous size distributions. The synthesis magnetic fluorescent NPs optimized was determined to have the injection temperature of Fe(CO)(5) at 60 degrees C, Fe(CO)(5)/CdSe@ZnS ratio 0.7, OAm/Fe(CO)(5) volume ratio 1.43 with an oxidation time 5 min. Under these conditions, the quantum efficiency was found to be 78 %, nanoparticle sizes between 11-14 nm and r(1) value was 0.199, r(2) value was 0.518 in MRI analysis. These optically active magnetic fluorescent nanoparticles as positive contrast agents (T1 weighted) are predicted to pave the way for the future of advanced bio-imaging systems.Article Citation - WoS: 15Citation - Scopus: 16Natural Molecule-Incorporated Magnetic Organic-Inorganic Nanoflower: Investigation of Its Dual Fenton Reaction-Dependent Enzyme-Like Catalytic Activities With Cyclic Use(Wiley-VCH Verlag GmbH, 2023-04-03) Dadi, Seyma; Cardoso, Marlon Henrique; Mandal, Amit Kumar; Franco, Octavio Luiz; Ildiz, Nilay; Ocsoy, IsmailThe functional organic-inorganic hybrid nanoflowers (hNFs) have recently attracted considerable attention due to enhanced catalytic activity and stability. The main purpose of this study is to synthesize new Fenton reagents and investigate their catalytic activity, dye degradation performance and antimicrobial activity. This magnetic gallic acid nanoflowers (FeGANF) were self-assembled via incorporating magnetic nanoparticles (Fe3O4 NPs) into gallic acid (GA) as organic part and copper(II) phosphate (Cu-3(PO4)(2)) as inorganic parts. The FeGANF were characterized by SEM, EDX, FT-IR and XRD. The peroxidase-like activity and dye degradation performance of FeGANF and GANF based on Fenton reaction in the presence of H2O2 was studied toward guaiacol as substrate, using methylene blue (MB) and congo red (CR) as a cationic and anionic dyes, respectively. FeGANF shows much high catalytic activity and decoloration efficiency (97 % for MB and 99 % for CR) because of dual active center in Fenton reaction on the surface of FeGANF. FeGANF exhibited more antimicrobial activity against Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 25923, and Candida albicans ATCC 10231 than that of the GA and GANF. The results of these studies suggest that magnetic hNFs has proved to be promising Fenton reagents for biological and environmental applications including treatment of wastewater.Article Citation - WoS: 6Citation - Scopus: 7Measuring Temperature Change at the Nanometer Scale on Gold Nanoparticles by Using Thermoresponsive PEGMA Polymers(Wiley-VCH Verlag GmbH, 2017-06-13) Yavuz, Mustafa S.; Citir, Murat; Cavusoglu, Halit; Demirel, GokhanPlasmonic heating of gold nanoparticles (AuNPs) under laser illumination is a highly desirable technique, especially for cancer therapy. However, significant drawbacks still remain including uncontrolled heat release from AuNPs, random exposure duration, and selection of the proper laser power without damaging normal healthy cells. Herein, we demonstrate a simple and versatile method to measure temperature variation on the surface of Au nanoparticles under laser irradiation based on a thermoresponsive polymer, poly(ethylene glycol) methylether methacrylate (PEGMA). In this context, a series of PEGMA polymers were synthesized to have different lower critical solution temperature (LCST) values (28-90 degrees C) and conjugated to the surface of spherical AuNPs by a gold-thiolate linkage. According to our strategy, the AuNPs first photothermally absorb light energy and convert it to heat owing to their tailored photothermal characteristics. The generated heat from the AuNPs subsequently dissipates into the surrounding thermoresponsive PEGMA polymer. When the temperature generated on the Au surface upon laser irradiation for a certain exposure time reaches the LCST value of the surrounding PEGMA polymer, the polymer chain collapses. Therefore, the hydrodynamic diameter of the PEGMA-coated AuNPs changes, which can be easily monitored by using dynamic light scattering (DLS). We systematically measured the temperature (28-90 degrees C) generated on the AuNP surfaces by using different laser power densities with varying durations. We believe that the resulting strategy will be very valuable for oncologists to easily predict the minimum laser power and duration needed to destroy the cancer cells through the photothermal effect of Au nanostructures.Article Citation - WoS: 6Citation - Scopus: 8Evaluation of Anti-Alzheimer Activity of Synthetic Coumarins by Combination of in Vitro and in Silico Approaches(Wiley-VCH Verlag GmbH, 2022-11-14) Orhan, Ilkay Erdogan; Deniz, F. Sezer Senol; Salmas, Ramin Ekhteiari; Irmak, Sule; Acar, Ozden Ozgun; Turgut, Gurbet Celik; Tataringa, Gabriela; Erdogan Orhan, IlkaySeries of synthetic coumarin derivatives (1-16) were tested against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), two enzymes linked to the pathology of Alzheimer's disease (AD). Compound 16 was the most active AChE inhibitor with IC50 32.23 +/- 2.91 mu M, while the reference (galantamine) had IC50=1.85 +/- 0.12 mu M. Compounds 9 (IC(50)75.14 +/- 1.82 mu M), 13 (IC50=16.14 +/- 0.43 mu M), were determined to be stronger BChE inhibitors than the reference galantamine (IC50=93.53 +/- 2.23 mu M). The IC50 value of compound 16 for BChE inhibition (IC50=126.56 +/- 11.96 mu M) was slightly higher than galantamine. The atomic interactions between the ligands and the key amino acids inside the binding cavities were simulated to determine their ligand-binding positions and free energies. The three inhibitory coumarins (9, 13, 16) were next tested for their effects on the genes associated with AD using human neuroblastoma (SH-SY5Y) cell lines. Our data indicate that they could be considered for further evaluation as new anti-Alzheimer drug candidates.Article Citation - WoS: 21Citation - Scopus: 21Enhancement of Anhydrous Proton Conductivity of Poly(Vinylphosphonic Acid)-Poly(2,5 Membranes Via in Situ Polymerization(Wiley-VCH Verlag GmbH, 2014-10-16) Sen, Unal; Usta, Hakan; Acar, Oktay; Citir, Murat; Canlier, Ali; Bozkurt, Ayhan; Ata, AliPolymer electrolyte membranes (PEMs) are synthesized via in situ polymerization of vinylphosphonic acid (VPA) within a poly(2,5-benzimidazole) (ABPBI) matrix. The characterization of the membranes is carried out by using Fourier transform infrared (FTIR) spectroscopy for the interpolymer interactions, thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) for the thermal properties, and scanning electron microscopy (SEM) for the morphological properties. The physicochemical characterizations suggest the complexation between ABPBI and PVPA and the formation of homogeneous polymer blends. Proton conductivities in the anhydrous state (150 degrees C) measured by using impedance spectroscopy are considerable, at up to 0.001 and 0.002 S cm(-1) for (1: 1) and (1: 2) molar ratios, respectively. These conductivities indicate signifi cant improvements (> 1000x) over the physically blended samples. The results shown here demonstrate the great potential of in situ preparation for the realization of new PEM materials in future high-temperature and non-humidified polymer electrolyte membrane fuel cell (PEMFC) applications.Article Discovery of New Candidates Targeting the SH2 Domains of Spleen Tyrosine Kinase (Syk) Through in Silico Studies(Wiley-VCH Verlag GmbH, 2025-06) Sansacar, Merve; Sari, Ceyhun; Yucel, Muhsin Samet; Akcok, Emel Basak Gencer; Akcok, Ismail; Gencer Akçok, Emel BaşakSrc homology 2 (SH2) domains have become an increasingly popular candidate for researchers to search for novel therapeutics to target different diseases. Spleen tyrosine kinase (Syk) is one of the proteins with two SH2 domains that has a role in the pathogenesis of many diseases. Here, we report the discovery of a promising natural product (NP) inhibitor that targets the N-terminal SH2 (N-SH2) and C-terminal SH2 (C-SH2) domains of Syk simultaneously, through structure-based drug discovery approach. Molecular docking studies, followed by molecular dynamics (MD) simulations and molecular mechanics Poisson-Boltzmann surface area (MM/PBSA) calculations, were utilized to reveal the interactions between NPs from "the COlleCtion of Open NatUral producTs (COCONUT)" database and Syk enzyme. Five natural products that have lowest Scoring and Minimization with AutoDock Vina (SMINA) scores against both SH2 domains of Syk were selected for further studies and compound CNP0265345 has the best binding free energies toward both C-SH2 and N-SH2 of Syk enzyme with -44.54 and -55.98 kcal/mol, respectively. Drug-likeness properties, absorption, distribution, metabolism, and excretion (ADME) and carcinogenicity predictions were also studied. In conclusion, our work highlights a novel drug candidate to target the Syk enzyme of SH2 domains using in silico methods.Article Citation - WoS: 29Citation - Scopus: 30A Solution-Processable Liquid-Crystalline Semiconductor for Low-Temperature Air-Stable N-Channel Field-Effect Transistors(Wiley-VCH Verlag GmbH, 2017-02-22) Ozdemir, Resul; Choi, Donghee; Ozdemir, Mehmet; Kim, Hyekyoung; Kostakoglu, Sinem Tuncel; Erkartal, Mustafa; Usta, HakanA new solution-processable and air-stable liquid-crystalline nchannel organic semiconductor (2,2'-(2,8-bis(5-(2-octyldodecyl) thiophen-2-yl) indeno[1,2-b] fluorene-6,12-diylidene) dimalononitrile, alpha,omega-2OD-TIFDMT) with donor-acceptor-donor (D-AD) pi conjugation has been designed, synthesized, and fully characterized. The new semiconductor exhibits a low LUMO energy (-4.19 eV) and a narrow optical bandgap (1.35 eV). The typical pseudo-focal-conic fan-shaped texture of a hexagonal columnar liquid-crystalline (LC) phase was observed over a wide temperature range. The spin-coated semiconductor thin films show the formation of large (approximate to 0.5-1 mu m) and highly crystalline platelike grains with edge-on molecular orientations. Low-temperature-annealed (50 degrees C) top-contact/bottom-gate OFETs have provided good electron obility values as high as 0.11 cm(2) (Vs)(-1) and high I-on/I-off ratios of 10(7) to 10(8) with excellent ambient stability. This indicates an enhancement of two orders of magnitude (100 V) when compared with the b-substituted parent semiconductor, beta-DD-TIFDMT (2,2'-(2,8-bis(3-dodecylthiophen- 2-yl) indeno[1,2-b] fluorene-6,12-diylidene) dimalononitrile). The current rational alkyl-chain engineering route offers great advantages for D-A-D pi-core coplanarity in addition to maintaining good solubility in organic solvents, and leads to favorable optoelectronic/physicochemical characteristics. These remarkable findings demonstrate that alpha,omega-2OD-TIFDMT is a promising semiconductor material for the development of n-channel OFETs on flexible plastic substrates and LC-state annealing of the columnar liquid crystals can lower the electron mobility for transistor-type charge transport.Article Citation - WoS: 23Citation - Scopus: 23Pressure-Induced Amorphization of MOF-5: A First Principles Study(Wiley-VCH Verlag GmbH, 2018) Erkartal, Mustafa; Durandurdu, Murat; Erkartal, Mustafa; Durandurdu, MuratAmorphous metal-organic frameworks (MOFs) and the amorphization of crystalline MOFs under mechanical stimuli are attracting considerable interest in last few years. However, we still have limited knowledge on their atomic arrangement and the physical origin of crystalline-to-amorphous phase transitions under mechanical stimuli. In this study, ab initio simulations within a generalized gradient approximation are carried out to investigate the high-pressure behavior of MOF-5. Similar to the previous experimental findings, a pressure-induced amorphization is observed at 2 GPa through the simulations. The phase transformation is an irreversible first order transition and accompanied by around 68% volume collapse. Remarkably, the transition arises from local distortions and, contrary to previous suggestions, does not involve any bond breaking and formation. Additionally, a drastic band gap closure is perceived for the amorphous state. This study has gone some way towards enhancing our understanding of pressure-induced amorphization in MOFs.