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Publication Restricted Molecular Modeling, DFT Quantum Chemical Analysis, and Molecular Docking on Edotecarin, an Indolocarbazole Anticancer Agent(Taylor & Francis Ltd., 2022) Çelik, Sefa; AKYÜZ, SEVİM; Özel, Ayşen E.Edotecarin is an indolocarbazole class antitumor agent that has significant anticancer effects against various types of cancer, especially lung, breast, and stomach cancer.The conformation analysis of the edotecarin was performed using the PM3 method and six stable conformations were obtained.Afterwards the obtained lowest energy conformation was optimized at the DFT/B3LYP/6-31++G(d,p) level of theory. The vibrational wavenumbers, the highest occupied molecular orbital, the lowest unoccupied molecular orbital and molecular electrostatic potential of the most stable conformer of edotecarin were calculated at the DFT/B3LYP/6-31++G(d,p) level of theory.The molecular docking of the edotecarin molecule against DNA, Topoisomerase I, DNA-Topoisomerase I complex,alpha(5)beta(1) and alpha(IIb)beta(3) integrins were performed to reveal its binding modes and binding affinities.Publication Restricted Molecular Structure, Molecular Docking and Absorption, Distribution, Metabolism, Excretion and Toxicity study of Cellulose II(Wiley-VCH Verlag GmbH, 2021) Çelik, Sefa; Demirağ, Aliye Demet; Özel, E. Ayşen; AKYÜZ, SEVİMCellulose is a renewable biopolymer which is the most abundant in nature, formed by binding of glucose units with beta-1,4 glycosidic bonds. Cellulose is divided into two groups as bacterial cellulose (BC) and vegetable cellulose. This study reports the interaction mechanism of Cellulose II, which is a BC, with the cellulase enzymes, determined by molecular docking method based on key-lock theory. The most stable molecular geometry of the Cellulose II molecule was determined by density functional theory using Gaussian 09 program. The scaled vibration frequencies of optimized geometry were calculated by using Molvib program. Molecular electrostatic potential and frontier molecular orbital analyses were performed. Molecular interactions between cellulose II and endoglucanase, exogluconase and beta-glucosidase II have been determined. Moreover, the drug likeness and ADMET properties of cellulose II were analyzed for the prediction of pharmacokinetic profiles.Publication Open Access Interactions Mechanism of Commonly Used Drugs for the Treatment of COVID-19(Bulletin of the Chemical Society of Ethiopia, 2020) Çelik, Sefa; Demirağ, A. Demet; Özel, Ayşen E.; AKYÜZ, SEVİMIn this study conformation analysis of seven drugs commonly used in the treatment of COVID-19 was performed. The most stable conformers of the drug molecules were used as initial data for docking analysis. Using the Cavityplus program, the probable most active binding sites of both apo and holo forms of COVID-19 main protease enzyme (M-P(ro)) and spike glycoprotein of SARSCoV-2 receptors were determined. The interaction mechanisms of the 7 FDA approved drugs (arbidol, colchicine, dexamethasone, favipiravir, galidesivir, hydroxychloroquine, remdesivir) were examined using the AutoDock Vina program. The six of the seven drugs were found to be more stable in binding to apo form of COVID-19 M-P(ro) and spike glycoprotein. Moreover, a set of molecular mechanics (MM) Poisson-Boltzmann (PB) surface area (SA) calculations on the investigated drugs-protein systems were performed and the estimated binding free energy of remdesivir and the apo form of MP' system was found to be the best. The interaction results of FDA drugs with the apo form of COVID-19 M-P(ro) and spike glycoprotein can play an important role for the treatment of COVID-19.Publication Restricted Structural and Vibrational Investigations and Molecular Docking Studies of a Vinca Alkoloid, Vinorelbine(Taylor & Francis Inc., 2022) Çelik, Sefa; AKYÜZ, SEVİM; Özel, Ayşen E.Vinorelbine, a vinca alkaloid, is an antimitotic drug that inhibits polymerisation process of tubulins to microtubules, and is widely used in cancer chemotherapy. Due to the importance of the structure-activity relationship, in this work the conformational preferences of the vinorelbine molecule were surched by PM3 method. The obtained lowest energy conformer was then optimized at DFT/B3LYP/6-31G(d,p) level of theory and the structural characteristics were determined. Frontier orbital (HOMO, LUMO) and molecular electrostatic potential (MEP) analyses were performed for the optimized structure. The experimental FT-IR, Raman and UV-VIS spectral data of vinorelbine along with the theoretical DFT/B3LYP/6-31G(d,p) calculations were investigated in detail. The vibrational wavenumbers were assigned based on the calculated potential energy distribution (PED) of the vibrational modes. To shed light into the anticancer property of vinorelbine as microtubule destabilizer, the most favourable binding mode and the interaction details between vinorelbine and tubulin were revealed by molecular docking studies of vinorelbine into the alpha,beta-tubulin (PDB IDs: 4O2B; 1SA0; 7CNN) and binding free energies were calculated by the combination of Molecular Mechanics/Generalized Born Surface Area (MMGBSA) and Molecular Mechanics/Poisson-Boltzmann Surface Area (MM-PBSA) methods {MM/PB(GB)SA}. The calculated vinorelbine-7CNN binding free energy, using by MM/PB(GB)SA approach, was found to be the best (-50.39 kcal/mol), and followed by vinorelbine-4O2B (-28.5 kcal/mol) and vinorelbine-1SA0 (-17.59 kcal/mol) systems. Moreover, the interaction of vinorelbine with the cytochrome P450 enzymes (CYP), which are known to help in the metabolism of many drugs in the body, was investigated by docking studies against CYP2D6 and CYP3A4 targets. Communicated by Ramaswamy H. SarmaPublication Restricted Synthesis, FT-IR and NMR Characterization, Antibacterial and Antioxidant Activities, and DNA Docking Analysis of a New Vanillin-Derived imine Compound(Elsevier, 2021) Çelik, Sefa; Özkök, Funda; Özel, Ayşen E.; Çakır, Elif; AKYÜZ, SEVİMA new vanillin-derived imine compound, [5-((1E,15E)-16-(3-methoxy-4-hydroxyphenyl)hexadeca-1',15'-diimine)-2-methoxyphenol], was synthesized and characterized by DFT calculations, experimental and theoretical vibrational spectroscopy and NMR techniques. The most stable molecular structure of the title compound has been calculated by optimizing the molecular structures using DFT/B3LYP/6-311+G(d,p) level of theory. The fundamental vibrational wavenumbers, IR and Raman intensities for the optimized geometry of the compound under investigation were determined and compared to the experimental vibrational spectra. The vibration assignment of the molecule was made in accord with the potential energy distribution (PED) of the vibration modes and using the group frequencies. The molecular electrostatic potential (MEP), HOMO and LUMO orbitals were also calculated. The antibacterial activities of the new vanillin-derived imine compound against gram-positive and gram-negative bacteria was determined. The antioxidant activity of the title compound was also examined. Moreover, the molecular docking studies have been performed to understand the nature of binding of the compound with DNA. The results indicated that the investigated compound has a good binding affinity with DNA and interacted with the DG4 and DT7 residues via the intermolecular hydrogen bonds.Publication Open Access Synthesis, Molecular Modelling, FT-IR, Raman and NMR Characterization, Molecular Docking and ADMET Study of New Nickel(II) Complex with an N4-Tetradentate Thiosemicarbazone(Taylor and Francis Ltd., 2021) Eğlence-Bakır, Songül; Çelik, Sefa; Şahin, Musa; Ozel, Ayşen E.; AKYÜZ, SEVİM; Ülküseven, BahriA new nickel(II) complex was synthesized by using S-propyl-thiosemicarbazide and 2-amino-3,5-dibromobenzaldehyde. The complex, obtained by the template effect of nickel ions, was structurally analysed by experimental and theoretical vibrational spectroscopy, NMR and density functional theory (DFT) calculations. By using DFT/B3LYP method with 6-311++G(d, p) basis set, the most stable molecular structure of the title molecule was calculated. The fundamental vibrational wavenumbers, IR and Raman intensities for the optimized structure of the molecule under investigation were determined and compared with the experimental vibrational spectra. The vibrational assignment was achieved using the calculated potential energy distributions of the vibrational modes. Moreover, the molecular electrostatic potential (MEP), the highest occupied molecular orbital (HOMO) and the lowest occupied molecular orbital (LUMO) energies were calculated, Molecular docking of the molecule was carried out against DNA in order to identify the potential inhibitory action of the title compound. The findings suggested that the aforementioned compound has a strong binding affinity to interact with DNA residues DT8, DC9, DG12, DG16, DA17, and DA18 through the intermolecular hydrogen bonds. Also the performed in silico ADMET analysis was the prediction of the synthesized molecule’s pharmacokinetic and toxicity profile expressing good oral drug like actions and non-toxic nature. The complex has been shown to have the possibility to become a model molecule for drug development processes. Communicated by Ramaswamy H. Sarma. © 2020 Informa UK Limited, trading as Taylor & Francis Group.Publication Restricted Molecular Modeling, Dimer Calculations, Vibrational Spectra, and Molecular Docking Studies of 5-Chlorouracil(Springer, 2020) Akalın E.; Çelik S.; AKYÜZ, SEVİMThe structure and vibrational calculations of 5-chlorouracil (5-ClU) and its most stable dimer have been analyzed using the DFT method with B3LYP/6-31++G(d,p) and wb97xd/6-31++G(d,p), respectively. Vibrational calculations of the monomeric and dimeric forms were performed using both harmonic and anharmonic oscillator approximations with the same basis sets. A complete vibrational analysis of the molecule has been performed by combining experimental Raman, FT-IR spectral data and quantum chemical calculations. In addition, the DNA docking analysis of 5-ClU molecule was performed. A 5-ClU molecule binds to the active site of DNA by hydrogen bonding interactions. The results show that the docked ligand formed a stable complex with DNA with binding affi nity of –5.3 kcal/mol.Publication Restricted Structural and Spectral Analysis of Anticancer Active Cyclo(Ala-His) Dipeptide(Taylor & Francis Inc., 2020) Çelik, Sefa; YILMAZ, GÖZDE; Özel, Ayşen E.; AKYÜZ, SEVİMThe theoretically possible most stable conformation of the cyclic dipeptide, which has a significant anticancer activity, was examined by conformational analysis method and then by DFT calculations. With DFT calculations, cyclo(Ala-His) dipeptide was found to be more stable in boat form than in planar conformation. Moreover, conformations of the dimeric forms of the title molecule were investigated. The dimeric forms of the cyclo(Ala-His) dipeptide were created by combining two identical cyclo(Ala-His) monomers, in lowest energy configuration and as a result three energetically possible dimeric structures were obtained. The solid phase FTIR and Raman spectra of cyclo(Ala-His) have been recorded. The spectra were interpreted with the aid of quantum chemical calculations based on density functional theory, using B3LYP and wb97xd methods with 6-311++G(d,p) basis set, in order to elucidate structural and spectral properties of the investigated molecule. Experimental vibrational spectra are found to be in accord with the simulated vibrational spectra. The assignment of the vibrational modes was performed depending on the calculated potential energy distribution (PED).In slicomolecular docking of cyclo(Ala-His) was also carried out with DNA. The drug likeness and ADMET properties were analyzed for the prediction of pharmacokinetic profiles. The results revealed that the compound has the potential to be the leading molecule in the drug discovery process.Publication Restricted Structural Characterization and Drug Delivery System of Natural Growth-Modulating Peptide Against Glioblastoma Cancer(Springer, 2021) Budama-Kılınç, Yasemin; Keçel-Gündüz, Serda; Çakır-Koç, Rabia; Aslan, Bahar; Bıçak, Bilge; Kökçü, Yağmur; Özel, Ayşen E.; AKYÜZ, SEVİMThe aim of the current study was to design a drug delivery nano-system of natural growth-modulating peptide known as GHK that naturally occurs in human plasma, saliva, and urine and determine possible anticancer activity against glioblastoma cancer based on in-silico and in-vitro evaluations. In this current study, a drug delivery nano-system based on Poly(epsilon-caprolactone) (PCL) were prepared by a double emission-precipitation method with different preparation parameters for optimization. The characterization of the optimum nanoparticles was performed with Zeta-Sizer, Ultraviolet-Visible (UV-Vis), Fourier Transform Infrared spectroscopy (FT-IR) and Raman spectroscopy, and Transmission Electron Microscopy (TEM) methods. The optimum size of the GHK loaded PCL nanoparticle was prepared with a 232.5 +/- 0.72 nm average particle size, - 10.8 +/- 0.64 mV zeta potential, and a 0.029 polydispersity index, 82.3% of encapsulation efficiency and 73% of loaded efficiency. In vitro cytotoxicity test revealed that the GHK loaded PCL nanoparticles had anticancer effect on glioblastoma cells. In vitro release study showed the sustained release behavior of GHK from nanoparticles during the period of 10 days study. In addition, molecular dynamics and molecular docking calculations, in vitro release study, and cytotoxicity tests showed that GHK loaded PCL nanoparticles may be used effectively for glioblastoma cancer therapy.Publication Open Access Synthesis, Antimicrobial Activity, Molecular Docking and ADMET Study of a Caprolactam-Glycine Cluster(Taylor & Francis Inc., 2021) Çelik, Sefa; Albayrak, Ali Tuğrul; AKYÜZ, SEVİM; Özel, Ayşen E.; Sığırcı, Belgi DirenDensity functional theory calculations were performed with DFT method using both b3lyp/6-311++G(d,p) and wb97xd/6-311++G(d,p) levels of theory to predict the molecular geometry, to evaluate the molecular electrostatic potential and frontier molecular orbitals of synthesized a new compound: caprolactam-glysine cluster (CL-Gly). Molecular docking study of the CL-Gly was carried out to clarify the interaction and the probable binding modes, between the title compound and DNA. The antibacterial activities of CL-Gly cluster against Gram-positive and Gram-negative bacteria was determined. In silico ADMET study was also performed for predicting pharmacokinetic and toxicity profile of the synthesized cluster which expressed good drug-like behavior and non-toxic nature. It was revealed that the compound has importance in drug discovery process. Communicated by Ramaswamy H. Sarm