Person: DANIŞ, ÖZKAN
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DANIŞ
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ÖZKAN
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Publication Metadata only Comprehensive computational analysis of Theileria annulata enolase by comparative modeling and docking(ELSEVIER SCIENCE BV, 2016) DANIŞ, ÖZKAN; Mutlu, Ozal; Yakarsonmez, Sinem; Sariyer, Emrah; Danis, Ozkan; Dursun, Basak Yuce; Topuzogullari, Murat; Akbulut, Ekrem; Turgut-Balik, DilekPublication Metadata only Investigation of HMG-CoA reductase inhibitory and antioxidant effects of various hydroxycoumarin derivatives(WILEY-V C H VERLAG GMBH, 2020) OGAN, AYŞE; Ozalp, Lalehan; Danis, Ozkan; Yuce-Dursun, Basak; Demir, Serap; Gunduz, Cihan; Ogan, AyseCardiovascular diseases are one of the primary causes of deaths worldwide, and the development of atherosclerosis is closely related to hypercholesterolemia. As the reduction of the low-density lipoprotein cholesterol level is critical for treating these diseases, the inhibition of 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase, which is essentially responsible for cholesterol biosynthesis, stands out as a key solution to lower plasma cholesterol levels. In this study, we synthesized several dihydroxycoumarins and investigated their antioxidant and in vitro HMG-CoA reductase inhibitory effects. Furthermore, we carried out in silico studies and examined the quantum-chemical properties of the coumarin derivatives. We also performed molecular docking experiments and analyzed the binding strength of each coumarin derivative. Our results revealed that compoundIVdisplayed the highest HMG-CoA reductase inhibitory activity (IC50 = 42.0 mu M) in vitro. Cupric-reducing antioxidant capacity and ferric-reducing antioxidant power assays demonstrated that coumarin derivatives exhibit potent antioxidant activities. Additionally, a close relationship was found between the lowest unoccupied molecular orbital energy levels and the antioxidant activities.Publication Metadata only A study of Bos taurus muscle specific enolase; biochemical characterization, homology modelling and investigation of molecular interaction using molecular docking and dynamics simulations(ELSEVIER SCIENCE BV, 2018) DANIŞ, ÖZKAN; Sariyer, Emrah; Yakarsonmez, Sinem; Danis, Ozkan; Turgut-Balik, DilekTropical theileriosis caused by Theileria annulata obligate parasite that infect ruminant animals, including Bos taurus. The disease results massive economic losses in livestock production worldwide. Here we describe cloning, expression and both biochemical and structural characterization of beta enolase from Bos taurus in vitro and in silico. The interconversion of 2-phosphoglycerate to phosphoenolpyruvate was catalyzed by enolase is a metalloenzyme in glycolytic pathway and gluconeogenesis. Enolase from Bos taurus was cloned, expressed and the protein was purified at 95% purity using cobalt column by affinity chromatography. The optimum enzymatic activity was calculated at pH 6.5. For the first time in the literature, the kinetic parameters of the enzyme, Vmax and Km, were measured as 0.1141 mM/min and 0.514 mM, respectively. Besides, Bos taurus enolase 3-dimensional structure was built by homology modelling to be used in silico analyses. The interactions of the enzyme-substrate complex were elucidated by molecular dynamics simulations for 100 ns. These interactions were found to be the same as experimentally determined interactions in yeast. These results would enable further structure based drug design studies with the biochemical characterization of the host organism Bos taurus enolase enzyme in vitro and the elucidation of behavior of enzyme-substrate complex in silico. (C) 2018 Elsevier B.V. All rights reserved.Publication Metadata only Kumarin türevlerinin fizyolojik pH’da sığır serum albümine bağlanmasının spektral ve moleküler yerleştirme ile incelenmesi(2022-10-05) MELETLİ, FURKAN; DANIŞ, ÖZKAN; OGAN, AYŞE; Meletli F., Kazancıçok Z., Akın N., Danış Ö., Ogan A.Serum albümin, kan plazmasında en yaygın bulunan proteinlerden biridir. Ozmotik basıncın ayarlanması,kan pH’nın belirlenmesi ve serbest radikallerin azaltılması gibi birçok farklı fizyolojik görevlerinin yanı sırakanda bulunan endojen ve eksojen maddelerin (yağ asitleri, ilaçlar ve metabolitler vb.) taşınmasında birincilişlevi olan çok fonksiyonlu ve önemli bir proteindir. İlaçlar hedeflerine ulaşmak için kan plazmasındataşınırken kaçınılmaz olarak serum albümin ile etkileşime girmektedirler. Serum albümin ile ilaç etkileşimiilacın terapötik etkisi hakkında bilgi vermektedir. Bu etkileşimlerin incelenmesi ilaç kimyasında, tıpta,biyoteknolojide ve biyokimyada önemli bir araştırma alanıdır. Sığır serum albümin (BSA), 582 amino asitkalıntısından oluşan ve insan serum albümini ile %76 benzerliği olan bir proteindir. Düşük maliyetli olması,yaygın olarak bulunabilmesi ve saflaştırma işleminin kolay olması nedeniyle BSA, araştırmacılar tarafındanligandların proteine bağlanma çalışmaları için sıklıkla tercih edilen, protein-ilaç etkileşimleri ve bağlanmamekanizmalarının belirlenmesi için model olan bir taşıma sistemidir. Kumarinler bir benzen halkası ilebir α-piron halkasının kaynaşması sonucu oluşan benzopiron adı verilen bir bileşik sınıfının üyesidirler.Doğal olarak bitkilerde bulunabildiği gibi sentetik olarak da elde edilebilmektedir. Kumarinlerin sahipoldukları konjuge çift halka sistemleri, onları farklı araştırma alanları için ilginç moleküller haline getirmiştir.Kumarin türevleri geniş bir biyolojik aktivite yelpazesi sergilemektedirler. Bunlar arasında anti-oksidan,anti-enflamatuar, anti-bakteriyel, anti-viral, anti-tümör ve anti-koagülan özellikleri öne çıkmaktadır.Kumarinler tıpta ve özellikle ilaç endüstrisinde yaygın olarak kullanılmaktadırlar. Çalışmamızda uygunEmilim, Dağılım, Metabolizma ve Atılım (ADME) özelliklerine göre farmakokinetik ve farmakodinamiketkileri iyi olan daha önceden sentezlenmiş ve karakterize edilmiş kumarin türevlerinin BSA’ya bağlanmalarıve taşınmaları in silico ve in vitro yöntemlerle araştırılmıştır. In silico çalışmalarda moleküler yerleştirme(moleküler docking) ve in vitro çalışmalarda UV-vis absorbans, floresans gibi multi-spektroskopik yöntemlerkullanılmıştır. BSA ile kumarin türevlerinin etkileşimleri in silico ve in vitro yöntemlerle aydınlatılmıştır. Insilico çalışmalar sonucunda kumarinlerin bağlanma enerjileri, ligand verimliliği değerleriyle birlikte proteinligandetkileşimleri ve konformasyonları belirlenmiştir. Ayrıca in vitro multi-spektroskopik analizlerindeğerlendirilmesiyle; bileşikler BSA’nın floresans şiddetinde, absorbansında ve ikincil yapısında değişikliklerizlenmiş, kuençleşme mekanizmaları, bağlanma sabitleri ve bağlanma bölgelerinin sayıları belirlenmiştir.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 Biochemical and in silico Characterization of Recombinant L-Lactate Dehydrogenase of Theileria annulata(HUMANA PRESS INC, 2016) MUTLU, ÖZAL; Nural, Belma; Erdemir, Aysegul; Mutlu, Ozal; Yakarsonmez, Sinem; Danis, Ozkan; Topuzogullari, Murat; Turgut-Balik, DilekTheileria annulata is a parasite that causes theileriosis in cattle. Reports about drug resistance made essential to develop new drug. LDH of Theileria schizonts is the vital enzyme for its anaerobic metabolism. TaLDH gene was first cloned into pGEM-T cloning vector with two introns in our previous study. Here we report cloning of TaLDH without introns into pLATE 31 vector in E. coli BL21(DE3). Protein was in an inactive form. Two mutations were fixed to express the active protein. Protein was purified by affinity chromatography and evaluated by SDS-PAGE and size exclusion chromatography. Optimum pH of enzyme was performed in pH 7.5, and enzyme was stabilized at 20-40 A degrees C. Enzyme kinetics of recombinant TaLDH were found to be in the direction of pyruvate to lactate K (m) 0.1324 and K (i) 4.295 mM, k (cat) , 44.55/s and k (cat) /K (m) , 3.3693 x 10(5)/M/s. 3D structure of TaLDH was predicted, and possible drug binding sites were determined by homology modelling.Publication Metadata only İnsan monoamin oksidaz a ve b inhibitörleri olarak benzokumarin türevlerinin sentezi ve biyolojik olarak değerlendirilmesi(2015-05-07) DANIŞ, ÖZKAN; DEMİR, SERAP; OGAN, AYŞE; ERDEM, SAFİYE; Danış Ö., Yüce Dursun B., Demir S., Alparslan M., Ogan A., Erdem S.Publication Open Access Novel azole-urea hybrids as VEGFR-2 inhibitors: Synthesis, in vitro antiproliferative evaluation and in silico studies(2023-12-15) KULABAŞ, NECLA; DANIŞ, ÖZKAN; KÜÇÜKGÜZEL, İLKAY; Shirzad M. M., KULABAŞ N., Erdoğan Ö., Çevik Ö., Dere D., Yelekçi K., DANIŞ Ö., Küçükgüzel İ.The vascular endothelial growth factor receptor-2 (VEGFR-2) is a receptor tyrosine kinase known to be abnormally expressed in various malignant tumors, including breast cancer, and is considered one of the most important contributors to tumor angiogenesis. Sorafenib is one of many VEGFR-2 inhibitors that have received approval for clinical use from the US FDA in recent years. Accordingly, in this study, the synthesis of two new pyrazoles, six 1,3,4-oxadiazoles, four 1,3,4-thiadiazoles, and ten 1,2,4-triazole-3-thione derivatives having structural characteristics similar to sorafenib was carried out. A preliminary screening of synthesized compounds and known inhibitors sorafenib and staurosporine at 10 µM concentration on in vitro activity of VEGFR-2 was performed, and compounds 10c, 8a, and 11 g were identified as the most potent derivatives with% VEGFR-2 residual activities lower than 30%, and dose-dependent inhibition studies was carried out to determine the IC50 values of these inhibitors. Compound 10c was found to be the most potent inhibitor of VEGFR-2 activity with an IC50 value of 0.664 µM. The anti-proliferative activity of synthesized derivatives was assessed against a breast carcinoma (MCF-7) cell line, a triple negative human breast adenocarcinoma (MDA-MB-231) cell line, and noncancerous fibroblast cells (L929). Compound 8a displayed superior activity when compared to sorafenib against MCF-7 (7.69 fold) and MDA-MB-231 (1.52 fold) cell lines while displaying 3.75-fold less toxicity against the normal L929 cell line. Annexin V binding assay revealed that compound 8a significantly increased early and late apoptosis in MCF-7 cells and late apoptosis and necrosis in MDA-MB-231 cells. Computational studies such as molecular docking and ADMET evaluation were performed to elucidate the binding interactions and drug-likeness of the synthesized compounds. The results indicate that compound 8a could be a promising candidate for the development of a novel anti-angiogenic and anti-proliferative agent.Publication Metadata only Preparation, characterization, and in vitro evaluation of isoniazid and rifampicin-loaded archaeosomes(WILEY, 2018) OGAN, AYŞE; Attar, Azade; Bakir, Ceren; Yuce-Dursun, Basak; Demir, Serap; Cakmakci, Emrah; Danis, Ozkan; Birbir, Meral; Ogan, AyseThe ability of Archaea to adapt their membrane lipid compositions to extreme environments has brought in archaeosomes into consideration for the development of drug delivery systems overcoming the physical, biological blockades that the body exhibits against drug therapies. In this study, we prepared unilamellar archaeosomes, from the polar lipid fraction extracted from Haloarcula 2TK2 strain, and explored its potential as a drug delivery vehicle. Rifampicin and isoniazid which are conventional drugs in tuberculosis medication were loaded separately and together in the same archaeosome formulation for the benefits of the combined therapy. Particle size and zeta potential of archaeosomes were measured by photon correlation spectroscopy, and the morphology was assessed by with an atomic force microscope. Encapsulation efficiency and loading capacities of the drugs were determined, and in vitro drug releases were monitored spectrophotometrically. Our study demonstrates that rifampicin and isoniazid could be successfully loaded separately and together in archaeosomes with reasonable drug-loading and desired vesicle-specific characters. Both of the drugs had greater affinity for archaeosomes than a conventional liposome formulation. The results imply that archaeosomes prepared from extremely halophilic archaeon were compatible with the liposomes for the development of stable and sustained release of antituberculosis drugs.Publication Metadata only Alpha-Amylase Immobilization on Epoxy Containing Thiol-Ene Photocurable Materials(KOREAN SOC MICROBIOLOGY & BIOTECHNOLOGY, 2013) ÇAKMAKÇI, EMRAH; Cakmakci, Emrah; Danis, Ozkan; Demir, Serap; Mulazim, Yusuf; Kahraman, Memet VezirThiol-ene polymerization is a versatile tool for several applications. Here we report the preparation of epoxide groups containing thiol-ene photocurable polymeric support and the covalent immobilization of alpha-amylase onto these polymeric materials. The morphology of the polymeric support was characterized by scanning electron microscopy (SEM), and energy dispersive spectroscopy (EDS) coupled with SEM was used to explore the chemical composition. The polymeric support and the immobilization of the enzyme were characterized by FTIR analysis. SEM-EDS and FTIR results showed that the enzyme was successfully covalently attached to the polymeric support. The immobilization efficiency and enzyme activity of alpha-amylase were examined at various pH (5.0-8.0) and temperature (30-80 degrees C) values. The storage stability and reusability of immobilized alpha-amylase were investigated. The immobilization yield was 276 +/- 1.6 mg per gram of polymeric support. Enzyme assays demonstrated that the immobilized enzyme exhibited better thermostability than the free one. The storage stability and reusability were improved by the immobilization on this enzyme support. Free enzyme lost its activity completely within 15 days. On the other hand, the immobilized enzyme retained 86.7% of its activity after 30 days. These results confirm that alpha-amylase was successfully immobilized and gained a more stable character compared with the free one.