PubMed İndeksli Yayınlar / PubMed Indexed Publications

Permanent URI for this collectionhttps://hdl.handle.net/11413/6357

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Molecular Docking of the Pentapeptide Derived From Rice Bran Protein as Anticancer Agent Inhibiting Both Receptor and Non-Receptor Tyrosine Kinases
(Taylor & Francis Inc., 2022) Gasymov, Oktay K; Keçel-Gündüz, Serda; Çelik, Sefa; AKYÜZ, SEVİM; Özel, Ayşen E.; Ağaeva, Gülşen; Süleymanova, Leman M.; Ağaeva, Ülker; Bakhishova, Matanat; Aliyev, JA
The cationic pentapeptide Glu-Gln-Arg-Pro-Arg (EQRPR) belongs to the family of anti-cancer peptides with significant anti-cancer activity. However, the mechanism by which the peptide performs this activity is unknown. In this study, we explored the pharmaceutical profile of Glu-Gln-Arg-Pro-Arg pentapeptide and revealed its anticancer properties by in silico docking studies. Moreover, the effect of EQRPR behavior of the DPPC membrane was investigated by means of Langmuir monolayer technique and the results were discussed in terms of mutual interactions. To evaluate the binding mechanisms, the pentapeptide and its various D-amino acid substituted analogs were docked to both epidermal growth factor receptor (EGFR) tyrosine kinase and proto-oncogene tyrosine-protein kinase, Fyn. Simultaneous binding of the pentapeptides to both EGFR and Fyn proteins, which are receptor- and non-receptor-kinases, respectively, suggest that these peptides can be an effective agent for cancer treatment. Moreover, to show the potential of the investigated pentapeptides to overcome the generated mutation-related drug resistance to EGFR targeted therapies, molecular docking investigations of EQRPR and all its D-analogs were performed against the prospective targets: Wild type EGFR(WT) and mutant EGFR(T790M). Erlotinib and TAK-285 were used as reference molecules. The strong interaction of the peptide with EGFR(WT) (from -9.24 to -9.75 kcal/mol) and the secondary mutant EGFR(T790M) (from -9.28 to -9.64 kcal/mol) observed in most cancer recurrence cases indicates its good potential to overcome drug resistance in cancer therapy. In addition, the pharmacological properties of the investigated pentapeptides were revealed by in silico ADME (Absorption, Distribution, Metabolism, Excretion) and toxicity analysis. Communicated by Ramaswamy H. Sarma
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Structural and Spectral Analysis of Anticancer Active Cyclo(Ala-His) Dipeptide
(Taylor & Francis Inc., 2020) Çelik, Sefa; YILMAZ, GÖZDE; Özel, Ayşen E.; AKYÜZ, SEVİM
The 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.
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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, Bahri
A 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.

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Browsing PubMed İndeksli Yayınlar / PubMed Indexed Publications by Subject "ADMET"