Biyoinformatik ve Genetik Bölümü Koleksiyonu

Permanent URI for this collectionhttps://hdl.handle.net/20.500.12469/46

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Citation - WoS: 22
Citation - Scopus: 25
Absolute Configuration and Biological Profile of Pyrazoline Enantiomers as Mao Inhibitory Activity
(Wiley, 2019) Goksen, Umut Salgin; Sarıgül, Sevgi; Bultinck, Patrick; Herrebout, Wouter; Doğan, İlknur; Yelekçi, Kemal; Uçar, Gülberk; Kelekçi, Nesrin Gökhan
A new racemic pyrazoline derivative was synthesized and resolved to its enantiomers using analytic and semipreparative high-pressure liquid chromatography. The absolute configuration of both fractions was established using vibrational circular dichroism. The in vitro monoamine oxidase (MAO) inhibitory profiles were evaluated for the racemate and both enantiomers separately for the two isoforms of the enzyme. The racemic compound and both enantiomers were found to inhibit hMAO-A selectively and competitively. In particular the R enantiomer was detected as an exceptionally potent and a selective MAO-A inhibitor (K-i = 0.85 x 10(-3) +/- 0.05 x 10(-3) mu M and SI: 2.35 x 10(-5)) whereas S was determined as poorer compound than R in terms of K-i and SI (0.184 +/- 0.007 and 0.001). The selectivity of the enantiomers was explained by molecular modeling docking studies based on the PDB enzymatic models of MAO isoforms.
Citation - WoS: 8
Citation - Scopus: 9
Antifungal Screening and in Silico Mechanistic Studies of an In-House Azole Library
(2019) Sarı, Suat; Kart, Didem; Sabuncuoğlu, Suna; Doğan, İnci Selin; Özdemir, Zeynep; Bozbey, İrem; Gencel, Melis; Eşsiz, Şebnem; Reynisson, Jóhannes; Karakurt, Arzu; Saraç, Selma; Dalkara, Sevim
Systemic Candida infections pose a serious public health problem with high morbidity and mortality. C. albicans is the major pathogen identified in candidiasis; however, non-albicans Candida spp. with antifungal resistance are now more prevalent. Azoles are first-choice antifungal drugs for candidiasis; however, they are ineffective for certain infections caused by the resistant strains. Azoles block ergosterol synthesis by inhibiting fungal CYP51, which leads to disruption of fungal membrane permeability. In this study, we screened for antifungal activity of an in-house azole library of 65 compounds to identify hit matter followed by a molecular modeling study for their CYP51 inhibition mechanism. Antifungal susceptibility tests against standard Candida spp. including C. albicans revealed derivatives 12 and 13 as highly active. Furthermore, they showed potent antibiofilm activity as well as neglectable cytotoxicity in a mouse fibroblast assay. According to molecular docking studies, 12 and 13 have the necessary binding characteristics for effective inhibition of CYP51. Finally, molecular dynamics simulations of the C. albicans CYP51 (CACYP51) homology model's catalytic site complexed with 13 were stable demonstrating excellent binding.
Citation - WoS: 2
Citation - Scopus: 3
Aryl Butenoic Acid Derivatives as a New Class of Histone Deacetylase Inhibitors: Synthesis in Vitro Evaluation and Molecular Docking Studies
(Scientific Technical Research Council Turkey-Tubitak, 2014) Esiyok, Peruze Ayhan; Seven, özlem; Eymur, Guluzar; Tatar, Gamze Bora; Erden, Didem Dayangaç; Yelekçi, Kemal; Yurter, Hayat; Demir, Ayhan S.
New aryl butenoic acid derivatives have been synthesized by combining hydroxy- or methoxy-substituted phenyl rings as the capping group with a double bond in the short linker as well as metal binding groups enoic ester and salts bearing either methyl or morpholine. These compounds have been shown to possess promising histone deacetylase inhibition activities via in vitro fluorometric assay and molecular docking studies.
Citation - WoS: 18
Citation - Scopus: 19
Carboxylic Acid Derivatives Display Potential Selectivity for Human Histone Deacetylase 6: Structure-Based Virtual Screening Molecular Docking and Dynamics Simulation Studies
(Elsevier Science, 2018) Uba, Abdullahi Ibrahim; Yelekçi, Kemal
Human histone deacetylase 6 (HDAC6) has been shown to play a major role in oncogenic cell transformation via deacetylation of alpha-tubulin making it a viable target of anticancer drug design and development. The crystal structure of HDAC6 catalytic domain 2 has been recently made available providing avenues for structure-based drug design campaign. Here in our continuous effort to identify potentially selective HDAC6 inhibitors structure-based virtual screening of similar to 72 461 compounds was carried out using Autodock Vina. The top 100 compounds with calculated Delta G < -10 kcal/mol were manually inspected for binding mode orientation. Furthermore the top 20 compounds with reasonable binding modes were evaluated for selectivity by further docking against HDAC6 and HDAC7 using Autodock4. Four compounds with a carboxylic fragment displayed potential selectivity for HDAC6 over HDAC7 and were found to have good druglike and ADMET properties. Their docking complexes were then submitted to 10 ns-molecular dynamics (MD) simulation using nanoscale MD (NAMD) software to examine the stability of ligand binding modes. These predicted inhibitors remained bound to HDAC6 in the presence of water and ions and the root-mean-square deviation (RMSD) radius of gyration (Rg) and nonbond distance (protein-ligand) profiles suggested that they might be stable over time of the simulation. This study may provide scaffolds for further lead optimization towards the design of HDAC6 inhibitors with improved selectivity. (C) 2018 Elsevier Ltd. All rights reserved.
Citation - WoS: 17
Citation - Scopus: 16
Cation Effect on Slow Release From Alginate Beads: a Fluorescence Study
(Springer/Plenum Publishers, 2014) Kaygusuz, Hakan; Erim, F. Bedia; Pekcan, Önder; Evingür, Gülşen Akin
In this study spherical alginate beads containing pyranine (P-y) as a fluorescence probe were prepared by ionotropic gelation of a sodium alginate solution. The steady state fluorescence technique was used to study pyranine release from the alginate beads crosslinked with calcium barium and aluminum ions respectively. The slow release of P-y was observed with the time drive mode of the spectrophotometer at 512 nm. Fluorescence emission intensity (I-p) from P-y was monitored during the release process and the encapsulation efficiency (EE) of pyranine from the alginate beads was calculated. The Fickian Diffusion model was used to measure the release coefficients D-sl. It was seen that the slow release coefficients of pyranine from the alginate beads crosslinked with Ca2+ Ba2+ and Al3+ ions increased in the following order: D-sl (Al3+)> D-sl (Ca2+)> D-sl (Ba2+). In contrast the initial amount of pyranine and EE into the beads showed the reverse behavior.
Collective Enhancement of Nuclear State Densities by the Shell Model Monte Carlo Approach
(IOP Publishing Ltd, 2015) Özen, Cem; Alhassid, Yoram; Nakada, Hitoshi
The shell model Monte Carlo (SMMC) approach allows for the microscopic calculation of statistical and collective properties of heavy nuclei using the framework of the configuration-interaction shell model in very large model spaces. We present recent applications of the SMMC method to the calculation of state densities and their collective enhancement factors in rare-earth nuclei.
Citation - WoS: 8
Citation - Scopus: 10
Controlling the Growth of Particle Size and Size Distribution of Silica Nanoparticles by the Thin Film Structure
(Springer, 2012) Uysal, Bengü Özuğur; Tepehan, Fatma Zehra
Nanostructured silicondioxide thin films were prepared by sol-gel spin coating technique. The SiO2 films were made using a conventional mixture of tetraethoxysilane (TEOS) deionized water and ethanol with various NH3/TEOS ratios. The nanostructured silica films were made using a mixture of the SiO2 sol and regular SiO2 sol to control the enlargement of the particles inside the films. The structural morphological and optical characterizations of the as-deposited and annealed films were carried out using X-ray diffraction (XRD) atomic force microscopy scanning electron microscopy NKD spectrophotometer and ultraviolet-visible (UV-vis) spectroscopy. The transmittance data of the infrared spectra of the films were recorded using an FT-IR Spectrometer. The XRD studies showed that as-deposited films were amorphous and the formation of the alfa-cristobalite phase of the silica film was investigated at annealing temperature close to 1100 A degrees C. Optical properties of the transmittance spectra in the s and p-polarization modes were collected. Refractive indices and extinction coefficients were determined with respect to the NH3/TEOS ratios in the compositions of the films. Optical cut-off wavelength values were investigated from the extrapolation of the absorbance spectra which was estimated from the UV-vis spectroscopy measurements. A red shift in the absorption threshold indicated that the size of silica nanoparticles was increased by an increase in the NH3/TEOS volume ratio from 1:64 to 1:8.
Citation - WoS: 2
Citation - Scopus: 3
Corrected Panel-Reactive Antibody Positivity Rates for Hypersensitized Patients in Turkish Population With Calculated Panel-Reactive Antibody Software
(Elsevier Science Inc, 2017) Karadeniz, Sedat Tanju; Akgül, Sebahat Usta; Öğret, Yeliz; Çiftçi, Hayriye Şentürk; Bayraktar, Adem; Bakkaloğlu, Hüseyin; Çalışkan, Yaşar Kerem; Yelekçi, Kemal; Türkmen, Aydin; Aydın, Ali Emin; Oğuz, Fatma Savran; Çarin, Mahmut Nezih; Aydın, Filiz
however the rate was 86.2% using the cPRA. Discussion. cPRA shows the rate of the rejected donors according to all unacceptable antigens. The need for a list of unacceptable antigens in place of the PRA positivity rate is a real change in the sensitization-dependent calculation as cPRA positivity rate. Conclusion. In principal implementation of cPRA will encourage many centers and laboratories to adopt a standard measurement of sensitization in Turkey. It will increase the chances of better donor match particularly for hypersensitized patients by the creation of an unacceptable mismatch program using cPRA software.
Citation - WoS: 21
Citation - Scopus: 20
Critical Exponents of Kappa Carrageenan in the Coil-Helix and Helix-Coil Hysteresis Loops
(Taylor & Francis Inc, 2009) Tarı, Özlem; Kara, Selim; Pekcan, Önder
The steady-state fluorescence technique was used to study coil-helix (sol-gel) and helix-coil (gel-sol) transitions of the kappa carrageenan-water system with various carrageenan contents. Fluorescence (I) and scattered light (I-sc) intensities were measured against temperature to determine critical phase transition temperatures and exponents. It was observed that the coil-helix transition temperatures T-ch were much lower than the helix-coil (T-hc) transition temperatures due to the hysteresis of the phase transition loops. The gel fraction exponent (beta) was measured and found to be in accord with the classical Flory-Stockmayer model.
Citation - WoS: 16
Citation - Scopus: 16
Critical Exponents of Photoinitiated Gelation at Different Light Intensities
(Taylor & Francis Inc, 2009) Doğruyol, Zekeriya; Arsu, Nergis; Pekcan, Önder
A photo-differential scanning calorimetric (Photo-DSC) technique was used to study the photoinitiated radical polymerization of a 75% epoxy diacrylate (EA) and 25% tripropyleneglycoldiacrylate (TPGDA) mixture with 2-mercaptothioxanthone (TX-SH) as photoinitiator by using different light intensities. Photopolymerization reactions were carried out under identical conditions of temperature and initiator concentration. It was observed that all conversion curves during gelation at various Might intensities present good sigmoidal behavior as predicted by the percolation model. Observations around the critical time called the glass transition point (t(g)) taken for polymerization to reach the maximum rate (R-pmax) show that the gel fraction exponents beta obeyed the universal percolation picture. On the other hand R-pmax t(g) and final conversion values were found to be dependent on the UV light intensity.
Citation - WoS: 6
Citation - Scopus: 11
Design, Synthesis and Hmao Inhibitory Screening of Novel 2-Pyrazoline Analogues
(Bentham Science Publ Ltd, 2017) Evranos-Aksöz, Begüm; Uçar, Gülberk; Yelekçi, Kemal
Aim and Objective: MAO inhibitors have a significant effect on the nervous system since they act in regulation of neurotransmitter concentrations. Neurotransmitter levels are critical for a healthy nervous system. MAO inhibitors can be used in the treatment of neurological disorders such as depression, Parkinson's disease and Alzheimer's disease, as the increase or decrease of some neurotransmitter concentrations is associated with these neurological disorders. This study was conducted to discover new and active MAO inhibitor drug candidates. Materials and Methods: New pyrazoline derivatives have been designed with the molecular docking approach and interactions of our compounds with the MAO enzyme have been investigated using the Autodock 4.2 program. The designed pyrazoline derivative compounds were synthesized by the reaction of the chalcones and hydrazides in ethanol. hMAO inhibitory activities of the newly synthesized compounds were investigated by fluorimetric method. In vitro cytotoxicity of five most potent inhibitors were tested in HepG2 cells. Results: (3-(5-bromo-2-hydroxyphenyl)-5-(4-methoxyphenyl)-4,5-dihydropyrazol-1-yl)(phenyl) methanone (5i) and (3-(2-hydroxy-4-methoxy phenyl)-5-p-tolyl-4,5-dihydropyrazol-1-yl)(phenyl) methanone (5l) inhibited hMAO-A more potently than moclobemide (Ki values are 0.004 +/- 0.001 and 0.005 +/- 0.001, respectively). The same two compounds, 5i and 5l, inhibited hMAO-A more selectively than moclobemide (SI values are 5.55x10(-5) and 0.003, respectively). Both of these compounds were found non toxic at 1 mu M, 5 mu M and 25 mu M concentrations. Conclusion: Two of the newly synthesized compounds, (3-(5-bromo-2-hydroxyphenyl)-5-(4-methoxyphenyl)- 4,5-dihydropyrazol-1-yl)(phenyl) methanone and (3-(2-hydroxy-4-methoxy phenyl)5- p-tolyl-4,5-dihydropyrazol-1-yl)(phenyl) methanone were found to be promising MAO-A inhibitors due to their high inhibitory potency, high selectivity and low toxicity.
Citation - WoS: 7
Citation - Scopus: 7
Design, Synthesis and in Vitro Cytotoxic Activity of New 6,9-Disubstituted Purine Analogues
(Slovensko Kemijsko Drustvo, 2020) Kuçükdumlu, Aslıgül; Tunçbilek, Meral; Bilget Güven, Ebru; Atalay, Rengül Çetin
A series of new 6,9-disubstituted purine analogs with 4-substituted piperazine at C-6 and 4-substituted benzyl at N-9 were designed and synthesized in four steps. All synthesized compounds (7-26) were screened initially for their in vitro anticancer activity on Huh7 liver, HCT116 colon and MCF7 breast carcinoma cell lines. Cytotoxic bioactivity studies revealed that all compounds screened, with compound 19 being the exception, were found to have promising cytotoxic activities at IC50 range of 0.05-21.8 mu M against cancer cells Huh7, HCT116 and MCF7. Among the prepared purine analogs, two of them (12 and 22) exhibited excellent cytotoxic activities, with IC50 0.08-0.13 mu M, on Huh7 cells comparable to camptothecin (CPT) and better than cladribine, fludarabine and 5-FU. Afterwards, the evaluation of cytotoxicity of the most potent purine analogs was screened against further hepatocellular cancer (HCC) cell lines. The 6-(4-(4-trifluoromethylphenyl)piperazine (12) and 6-(4-(3,4-dichlorophenyl)piperazine analogs (25) displayed a significant IC50 values (IC50 < 0.1-0.13 mu M) comparable to CPT and better cytotoxic bioactivity when compared with 5-FU, cladribine and fludarabine on HCC cells (Huh7 and HepG2).
Citation - Scopus: 1
Determination of Growth Kinetics and Size Dependent Structural Morphological Optical Characteristics of Sol-Gel Derived Silica Nanoparticles in Silica Matrix
(De Gruyter Poland Sp Zoo, 2019) Uysal, Bengü Özuğur; Tepehan, Fatma Zehra
Nanocomposite silica thin films made using the sol-gel method were studied. The nano-silica films were prepared using a mixture of tetraethyl orthosilicate (TEOS) deionized water ethanol and ammonia solution. To control the growth of the particles inside the film the nanocomposite silica film was prepared using a mixture of the nano-silica sol and the silica sol. The change in the particle size with the heat treatment temperature ranging from 450 degrees C to 1100 degrees C was investigated. X-ray diffraction (XRD) atomic force microscopy (AFM) scanning electron microscopy (SEM) NKD (refractive index-N extinction coefficient-K and thickness-D) and ultraviolet-visible (UV-Vis) spectrophotometry were used for characterization purposes. The XRD studies showed that the nano-silica thin films were amorphous at all annealing temperatures except for 1100 degrees C. The alpha-cristobalite crystal structure formed at the annealing temperature of 1100 degrees C. Optical parameters such as refractive indices and extinction coefficients were obtained using the NKD analyzer with respect to the annealing temperature of the films. The activation energy and enthalpy of the nanocomposite silica film were evaluated as 22.3 kJ/mol and 14.7 kJ/mol respectively. The cut-off wavelength values were calculated by means of extrapolation of the absorbance spectra estimated using the UV-Vis spectroscopy measurements. A red shift in the absorption threshold of the nanocomposite silica films indicated that the size of the silica nanoparticles increased with an increase of the annealing temperatures from 450 degrees C to 900 degrees C and this confirms the quantum confinement effect in the nanoparticles.
Citation - WoS: 59
Citation - Scopus: 57
Docking Studies on Monoamine Oxidase-B Inhibitors: Estimation of Inhibition Constants (k-I) of a Series of Experimentally Tested Compounds
(Pergamon-Elsevier Science Ltd, 2005) Toprakçı, Mustafa; Yelekçi, Kemal
Monoamine oxidase (EC1.4.3.4
Citation - WoS: 6
Citation - Scopus: 7
Drying of Polyacrylamide Composite Gels Formed With Various Kappa- Carrageenan Content
(Springer/Plenum Publishers, 2011) Evingür, Gülşen Akın; Pekcan, Önder
Drying of polyacrylamide (PAAm)-kappa-carrageenan (kappa C) composite gels were monitored by using steady-state fluorescence technique. Disc shaped gels were formed from acrylamide (AAm) and N N'- methylenebisacrylamide(Bis) with various kappa- carrageenan (kappa C) contents by free radical crosslinking copolymerization in water. Pyranine (P) was doped as a fluorescence probe and scattered light I (sc) and fluorescence intensities I were monitored during drying of these gels. It is observed that fluorescence intensity of pyranine increased as drying time is increased for all samples. The increase in I was modeled using Stern- Volmer equation and diffusion with moving boundary. It is found that desorption coefficient D decreased as kappa C contents were increased. Supporting gravimetrical and volumetric experiments were also carried out during drying of PAAm- kappa C composite gels.
Citation - WoS: 4
Citation - Scopus: 3
Drying of Polyacrylamide-Multiwalled Carbon Nanotube (mwnt) Composites With Various Mwnts Contents: a Fluorescence Study
(Walter De Gruyter Gmbh, 2013) Evingür, Gülşen Akin; Pekcan, Önder
We studied the drying of polyacrylamide (PAAm)-multiwalled carbon nanotube (MWNT) composites prepared by free radical crosslinking copolymerization in water with a steady state fluorescence technique. Composite gels were prepared at room temperature with pyranine (Py) doped as a fluorescence probe. Drying experiments were performed in air at various MWNT contents by real time monitoring of the Py fluorescence intensity (I) which increased as the drying proceeded. The Stern-Volmer equation combined with the moving boundary diffusion model was used to explain the behavior of I during drying. It was observed that the desorption coefficient (D) increased as the temperature increased. Drying energies (Delta E) were measured for the drying processes for each MWNT content gel by using fluorescence gravimetrical and volumetric methods. It is understood that Delta E values decrease by increasing MWNT content until 1 wt % MWNT and then increase above the level of this threshold value. The energy of drying is strongly correlated with the MWNT content in the composite. Delta E drops to its lowest value at which conducting cluster starts to appear.
Citation - WoS: 6
Citation - Scopus: 6
Effect of Calcium Ion Concentration on Small Molecule Desorption From Alginate Beads
(Taylor & Francis Inc, 2014) Evingür, Gülşen Akin; Kaygusuz, Hakan; Erim, F. Bedia; Pekcan, Önder
Spherical alginate beads were prepared by ionotropic gelation of sodium alginate through the use of calcium ions. Pyranine (Py) was added to the alginate solution as a small molecule probe for fluorescence studies. Desorption of Py in water from the alginate beads cross-linked with calcium ions was studied by using the steady state fluorescence technique. The fluorescence emission intensity (I) from Py was monitored during the desorption process at 512 nm using the time drive mode of the spectrofluorometer. The increase in I was attributed to Py release from the beads. The Fickian diffusion model was used to calculate the desorption coefficients D which were found to be increased up to 3% (w/v) CaCl2 concentration in the beads and then decreased with a further increase of CaCl2 content. On the other hand the encapsulation efficiency of Py in the calcium alginate beads presented the reverse behavior compared to D. It was observed that when the content of CaCl2 was increased the incubation time t(0) for the start of desorption increased.
Citation - WoS: 12
Citation - Scopus: 14
Elastic Percolation of Swollen Polyacrylamide (paam)-Multiwall Carbon Nanotubes Composite
(Taylor & Francis Ltd, 2012) Evingür, Gülşen Akin; Pekcan, Önder
Polyacrylamide (PAAm)-multiwalled carbon nanotube (MWNT) composites were prepared via free radical cross-linking copolymerization with different amounts of MWNTs varying in the range between 0.1 and 50 wt%. The mechanical properties of swollen PAAm-MWNT composites were characterized by the tensile testing technique. A small content of embedded nanotubes dramatically changes the compressive elastic modulus of the composites. Compressive elastic modulus dramatically increases up to 1wt% MWNT on increasing nanotube content and then decreases presenting a critical MWNT value indicating that there is a sudden change in the material elasticity. The critical exponent y of elasticity below the critical MWNT content 1 wt% is found to be 0.58 which is consistent with the suggestions of percolation in the superelastic percolation network for PAAm-MWNT composite.
Citation - WoS: 17
Citation - Scopus: 18
Electrical and Optical Percolations in Pmma/Gnp Composite Films
(Taylor & Francis Ltd, 2018) Arda, Ertan; Mergen, Omer Bahadir; Pekcan, Önder
Effects of graphene nanoplatelet (GNP) addition on the electrical conductivity and optical absorbance of poly(methyl methacrylate)/graphene nanoplatelet (PMMA/GNP) composite films were studied. Optical absorbance and two point probe resistivity techniques were used to determine the variations of the optical and electrical properties of the composites respectively. Absorbance intensity A and surface resistivity R-s of the composite films were monitored as a function of GNP mass fraction (M) at room temperature. Absorbance intensity values of the composites were increased and surface resistivity values were decreased by increasing the content of GNP in the composite. Electrical and optical percolation thresholds of composite films were determined as M-sigma = 27.5 wt.% and M-op = 26.6 wt.% respectively. The conductivity and the optical results were attributed to the classical and site percolation theories respectively. Optical ((op)) and electrical ((sigma)) critical exponents were calculated as 0.40 and 1.71 respectively.
Citation - WoS: 4
Citation - Scopus: 3
Electrical Optical and Fluorescence Percolations in P(vac-co-bua)/Mwcnt Composite Films
(Taylor & Francis Ltd, 2013) Arda, Ertan; Kara, Selim; Pekcan, Önder
Effects of multiwall carbon nanotube (MWCNT) addition on the electrical conductivities optical transparencies and fluorescence emissions of poly(vinyl acetate-co-butyl acrylate) (P(VAc-co-BuA))/MWCNT composite films were studied. Optical transmission fluorescence emission and two point probe resistivity techniques were used to determine the variations of the optical fluorescence and electrical properties of the composites respectively. Transmitted photon intensity (I-tr) fluorescence emission intensity (I-fl) and surface resistivity ((s)) of the composite films were monitored as a function of MWCNT mass fraction (M) at room temperature. All these measured quantities of the composites were decreased by increasing the content of MWCNT in the composite. The conductivity and the optical results were attributed to the classical and site percolation theories respectively. The fluorescence results however possessed both the site and classical percolation theories at low and high MWCNT content regions respectively.

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