Person: OGAN, AYŞE
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OGAN
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AYŞE
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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 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 Metadata only Anne sütünden insülin benzeri büyüme faktörü-I (igf-I) bağlayıcı proteinlerin ligand blot metodu ile analizi(2002-06-24) OGAN, AYŞE; Yeldan M., Ogan A.Publication Open Access In silico discovery of potential azole-containing mPGES-1 inhibitors by virtual screening, pharmacophore modeling and molecular dynamics simulations(2022-08-01) KÜÇÜKGÜZEL, İLKAY; OGAN, AYŞE; Ozalp L., KÜÇÜKGÜZEL İ., OGAN A.Inhibition of microsomal prostaglandin E-2 synthase-1 (mPGES-1) is promising for designing novel nonsteroidal anti-inflammatory drugs, as they lack side-effects associated with inhibition of cyclooxygenase enzymes. Azole compounds are nitrogen-containing heterocycles and have a wide use in medicine and are considered as promising compounds in medicinal chemistry. Various computer-aided drug design strategies are incorporated in this study. Structure-based virtual screening was performed employing various docking programs. Receiver operator characteristic (ROC) curves were used to evaluate the selectivity of each program. Furthermore, scoring power of Autodock4 and Autodock Vina was assessed by Pearson\"s correlation coefficients. Pharmacophore models were generated and Guner-Henry score of the best model was calculated as 0.89. Binding modes of the final 10 azole compounds were analyzed and further investigation of the best binding (- 8.38 kcal/mol) compound was performed using molecular dynamics simulation, revealing that furazan1224 (ZINC001142847306) occupied the binding site of the substrate, prostaglandin H-2 (PGH(2)) and remained stable for 100 ns. Continuous hydrogen bonds and hydrophobic interactions with amino acids in the active site supported the stability of furazan1224 throughout the trajectory. Pharmacokinetic profile showed that furazan1224 lacks the risks of inhibiting cytochrome P450 3A4 enzyme and central nervous system-related side-effects.Publication Open Access Identification of some novel amide conjugates as potent and gastric sparing anti-inflammatory agents: In vitro, in vivo, in silico studies and drug safety evaluation(2023-08-05) KULABAŞ, NECLA; DANIŞ, ÖZKAN; OGAN, AYŞE; ERDEM, SAFİYE; KÜÇÜKGÜZEL, İLKAY; KULABAŞ N., Set İ., Aktay G., GÜRSOY Ş., DANIŞ Ö., OGAN A., Sağ Erdem S., Erzincan P., Helvacıoğlu S., Hamitoğlu M., et al.Today, usage of NSAIDs (nonsteroidal anti-inflammatory drugs) is very common. However, it has been proven by many studies that NSAIDs with free carboxylic acid group damage the GI (gastrointestinal) system. Our aim was to mask the acidic groups of NSAIDs to prevent or reduce their side effects while preserving their pharmacological effects. In this study, new amide derivatives of known NSAIDs, compounds 11–20, were synthesized to investigate their analgesic and anti-inflammatory effects using in vivo models. While compound 11 showed the most remarkable anti-inflammatory activity by 60.9% inhibition value at 200 mg/kg dose, compounds 11, 12, 15 and 18 had almost the same analgesic activity to that of acetylsalicylic acid (100 mg/kg) and flurbiprofen (100 mg/kg). In addition, all test compounds used at high dose (200 mg/kg, p.o) did not show any acute toxicity. COX-1 and COX-2 inhibition properties of all compounds were measured by biochemical methods and the interaction of the most active compounds with COX enzymes is elucidated by computer-assisted virtual screening methods. It was determined by in vitro enzyme inhibition studies that compound 11 and 13, synthesized from selective COX-1 inhibitors dexketoprofen and flurbiprofen, are selective COX-2 inhibitors. Moreover, compounds 11–13 were found to be non-mutagenic according to the mutagenicity assay using Salmonella TA98 and TA100 strains with and without metabolic activation. Finally, the prediction of ADMET profile and drug-likeness properties of compounds 11–20 were examined and the obtained results were evaluated.Publication Open Access Synthesis and evaluation of antiproliferative and mPGES-1 inhibitory activities of novel carvacrol-triazole conjugates(2022-01-01) KULABAŞ, NECLA; DANIŞ, ÖZKAN; OGAN, AYŞE; Demirbolat İ., KULABAŞ N., Gürboğa M., Özakpınar Ö. B., Çiftçi G., Yelekçi K., Liu J., Jakobsson P., DANIŞ Ö., OGAN A., et al.Some novel triazole-bearing acetamide derivatives 9-26 were synthesized starting from carvacrol. All synthesized compounds were characterized by FTIR, 1H-NMR, 13C-NMR and MS data. In vitro cytotoxic activities of all synthesized molecules against five cancer lines (human breast cancer MCF-7, human lung cancer A549, human prostate cancer PC-3, human chronic myelogenous leukemia K562, human neuroblastoma SH-SY5Y cell lines) were evaluated by MTT assay. Compounds were also tested on mouse embryonic fibroblast cells (NIH/3T3) to determine selectivity. Eighteen target compounds 9-26 were screened for their mPGES-1 and COX-1/2 inhibitory activities. Of these compounds, 26 (KUC16D425) showed the highest mPGES-1 inhibition at 10 µM. This compound has also been observed to induce apoptosis and inhibit cell migration in MCF-7 cells. In silico molecular docking calculations were performed to understand the binding interactions of compounds with target proteins. ADMET predictions were also done to evaluate drug-like properties of the novel compounds.