Person: KÜÇÜKGÜZEL, İLKAY
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KÜÇÜKGÜZEL
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İLKAY
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Publication Open Access Determination of non-steroidal antiinflammatory drugs in equine biological samples by chromatographic methods [Yarış atlarında kullanımı suistimal edilen bazı non-steroidal antienflamatuvar ilaçların biyolojik örneklerden kromatografik yöntemlerle miktar tayini](Marmara University, 2012-01-01) TATAR, ESRA; Tatar E., Topçu S., Küçükgüzel I.In the knowledge that non-steroidal antiinflammatory drugs (NSAIDs) which are not included in the WADA's (World Anti-Doping Agency) list enacting doping substances and methods, have been abused in horse racing; a review on qualitative and quantitative determination of some of these non-steroidal antiinflammatory drugs (acetylsalicyclic acid, benzydamine, bufexamac, diclofenac sodium, diflunisal, eltenac, etodolac, etoricoxib, felbinac, phenylbutazone, flufenamic acid, flunixin, flurbiprofen, ibuprofen, indometacin, indoprofen, carprofen, ketoprofen, ketorolac, meclofenamic acid, mefenamic acid, meloxicam, mofebutazon, naproxen, niflumic acid, nimesulide, oxyphenbutazone, piroxicam, ramifenazone, selecoxib, sulindac, tenoxicam, tiaprofenic acid, tolfenamic acid, tolmetin, valdecoxib and vedaprofen) from biological samples of horses was gathered within the context of this work.Publication Open Access Novel 1,2,4-triazoles derived from Ibuprofen: synthesis and in vitro evaluation of their mPGES-1 inhibitory and antiproliferative activity(2022-11-01) BİNGÖL ÖZAKPINAR, ÖZLEM; KULABAŞ, NECLA; TATAR, ESRA; KÜÇÜKGÜZEL, İLKAY; Bulbul B., Ding K., Zhan C., Ciftci G., YELEKÇİ K., Gurboga M., BİNGÖL ÖZAKPINAR Ö., Aydemir E., Baybag D., ŞAHİN F., et al.Some novel triazole-bearing ketone and oxime derivatives were synthesized from Ibuprofen. 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 cervix cancer HeLa, and human chronic myelogenous leukemia K562 cell lines) were evaluated by MTT assay. In addition, mouse embryonic fibroblast cells (NIH/3T3) were also evaluated to determine the selectivity. Compounds 18, 36, and 45 were found to be the most cytotoxic, and their IC50 values were in the range of 17.46-68.76 mu M, against the tested cancer cells. According to the results, compounds 7 and 13 demonstrated good anti-inflammatory activity against the microsomal enzyme prostaglandin E2 synthase-1 (mPGES-1) enzyme at IC50 values of 13.6 and 4.95 mu M. The low cytotoxicity and non-mutagenity of these compounds were found interesting. Also, these compounds significantly prevented tube formation in angiogenesis studies. In conclusion, the anti-inflammatory and angiogenesis inhibitory activities of these compounds without toxicity suggested that they may be promising agents in anti-inflammatory treatment and they may be supportive agents for the cancer treatment.Publication Metadata only Synthesis, and prediction of molecular properties and antimicrobial activity of some acylhydrazones derived from N-(arylsulfonyl)methionine(SCIENTIFIC TECHNICAL RESEARCH COUNCIL TURKEY-TUBITAK, 2016) TATAR, ESRA; Tatar, Esra; Senkardes, Sevil; Sellitepe, Hasan Erdinc; Kucukguzel, Sukriye Guniz; Karaoglu, Sengul Alpay; Bozdeveci, Arif; De Clercq, Erik; Pannecouque, Christophe; Ben Hadda, Taibi; Kucukguzel, IlkayA series of 38 new acylhydrazones [3-40], derived from (2S)-4-(methylsulfanyl)-2-[[(4-methylphenyl)sulfonyl] amino]butanoic acid hydrazide [2], were synthesized and evaluated for their anti-HIV and antimicrobial activity with the further aim to develop acylhydrazones carrying an amino acid side chain. All tested compounds possess stronger activity against gram (+) bacteria. Compound 23 was found active against methicillin-resistant Staphylococcus aureus (MRSA) with a MIC value of 3.9 mu g/mL. The MIC value of compound 30 against Enterococcus faecalis, Listeria monocytogenes, and Bacillus cereus was 8 mu g/mL. A computational study for prediction of ADME and drug-like properties (solubility, drug-likeness, and drug score) as well as potential toxicity profiles of compounds 2-40 was performed using the Molinspiration online property calculation toolkit and Osiris Property Explorer. As most of our compounds meet Lipinski's rule of five, they promise good solubility and permeability. According to Osiris calculations, the majority of our compounds are supposed to be nonmutagenic and nonirritating.Publication Metadata only Synthesis and antiproliferative evaluation of novel 2-(4H-1,2,4-triazole-3-ylthio)acetamide derivatives as inducers of apoptosis in cancer cells(ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER, 2016) ÖZSAVCI, DERYA; Kulabas, Necla; Tatar, Esra; Ozakpinar, Ozlem Bingol; Ozsavci, Derya; Pannecouque, Christophe; De Clercq, Erik; Kucukguzel, IlkayIn this study, a series of thiosemicarbazide derivatives 12-14, 1,2,4-triazol-3-thione derivatives 15-17 and compounds bearing 2-(4H-1,2,4-triazole-3-ylthio)acetamide structure 18-32 have been synthesized starting from phenolic compounds such as 2-naphthol, paracetamol and thymol. Structures and purity of the target compounds were confirmed by the use of their chromatographic and spectral data besides microanalysis. All of the synthesized new compounds 12-32 were evaluated for their anti-HIV activity. Among these compounds, three representatives 18, 19 and 25 were selected and evaluated by the National Cancer Institute (NCI) against the full panel of 60 human cancer cell lines derived from nine different cancer types. Antiproliferative effects of the selected compounds were demonstrated in human tumor cell lines K-562, A549 and PC-3. These compounds inhibited cell growth assessed by MTT assay. Compound 18,19 and 25 exhibited anti-cancer activity with IC50 values of 5.96 mu M (PC-3 cells), 7.90 mu M (A549/ATCC cells) and 7.71 mu M (K-562 cells), respectively. After the cell viability assay, caspase activation and Bcl-2 activity of the selected compounds were measured and the loss of mitochondrial membrane potential (MMP) was detected. Compounds 18, 19 and 25 showed a significant increase in caspase-3 activity in a dose-dependent manner. This was not observed for caspase-8 activity with compound 18 and 25, while compound 19 was significantly elevated only at the dose of 50 mu M. In addition, all three compounds significantly decreased the mitochondrial membrane potential and expression of Bcl-2. (C) 2016 Elsevier Masson SAS. All rights reserved.Publication Open Access Design, Synthesis, and Molecular Docking Studies of a Conjugated-Thiadiazole Thiourea Scaffold as Antituberculosis Agents(PHARMACEUTICAL SOC JAPAN, 2016) TATAR, ESRA; Tatar, Esra; Karakus, Sevgi; Kucukguzel, Sukriye Guniz; Okullu, Sinem Oktem; Unubol, Nihan; Kocagoz, Tanil; De Clercq, Erik; Andrei, Graciela; Snoeck, Robert; Pannecouque, Christophe; Kalayci, Sadik; Sahin, Fikrettin; Sriram, Dharmarajan; Yogeeswari, Perumal; Kucukguzel, IlkayIn view of the emergence and frequency of multidrug-resistant and extensively drug-resistant tuberculosis and consequences of acquired resistance to clinically used drugs, we undertook the design and synthesis of novel prototypes that possess the advantage of the two pharmacophores of thiourea and 1,3,4-thiadiazole in a single molecular backbone. Three compounds from our series were distinguished from the others by their promising activity profiles against Mycobacterium tuberculosis strain H(37)Rv. Compounds 11 and 19 were the most active representatives with minimum inhibitory concentration (MIC) values of 10.96 and 11.48 mu m, respectively. Compound 15 was shown to inhibit M. tuberculosis strain H(37)Rv with an MIC value of 17.81 mu m. Cytotoxicity results in the Vero cell line showed that these three derivatives had selectivity indices between 1.8 and 8.7. In order to rationalize the biological results of our compounds, molecular docking studies with the enoyl acyl carrier protein reductase (InhA) of M. tuberculosis were performed and compounds 11, 15, and 19 were found to have good docking scores in the range of -7.12 to -7.83 kcal/mol.Publication Metadata only Fabrication and characterisation studies of cyclodextrin-based nanosponges for sulfamethoxazole delivery(SPRINGER, 2020) TATAR, ESRA; Yasayan, Gokcen; Sert, Betul Satiroglu; Tatar, Esra; Kucukguzel, Ilkaybeta-Cyclodextrin based nanosponges have been synthesized in three molar ratios, and characterized by phase solubility studies, Fourier-transform infrared spectroscopy, matrix-assisted laser desorption/ionization time of flight mass spectrometry, and scanning electron microscopy. Following characterization studies, a model anti-bacterial agent, sulfamethoxazole, has been loaded within the nanosponges, and in vitro drug release studies were carried out. According to results, nanosponges below similar to 100 nm diameter were obtained with a characteristic sponge-like morphology. Phase solubility studies demonstrated that beta-cyclodextrin nanosponges improve solubility of the drug up to 30-fold. These results suggest that nanosponges could improve the bioavailability of drugs by conducing them to reach desired plasma concentrations for therapeutic effect. [GRAPHICS] .Publication Metadata only Synthesis and evaluation of novel 1,3,4-thiadiazole-fluoroquinolone hybrids as antibacterial, antituberculosis, and anticancer agents(SCIENTIFIC TECHNICAL RESEARCH COUNCIL TURKEY-TUBITAK, 2018) TÜRE, ASLI; Demirci, Asli; Karayel, Kaan Gokce; Tatar, Esra; Oktem Okullu, Sinem; Unubol, Nihan; Tasli, Pakize Neslihan; Kocagoz, Zuhtu Tanil; Sahin, Fikrettin; Kucukguzel, IlkayA series of 5-substituted-1,3,4-thiadiazole-based fluoroquinolone derivatives were designed as potential antibacterial and anticancer agents using a molecular hybridization approach. The target compounds 16-25 were synthesized by reacting the corresponding N-(5-substituted-1,3,4-thiadiazol-2-yl)-2-chloroacetamides with ciprofloxacin or norfloxacin. The purity and identity of the synthesized compounds were determined by the use of chromatographic and spectral techniques (NMR, IR, MS, etc.) besides elemental analysis. Antibacterial, antituberculosis, and anticancer activity of the target compounds were evaluated against selected strains and cancer cell lines. Compound 20 was appreciated as the most active agent representing antibacterial activity against Escherichia coli and Staphylococcus aureus with MIC values of 4 mu g/mL and 2 mu g/mL, respectively. Amongst the synthesized fluoroquinolone derivatives, compounds 19 and 20 were found to have modest antitubercular activity with 8 mu g/mL MIC values for each. Most potent derivative, compound 20 was docked against Staphylococcus aureus and Mycobacterium tuberculosis DNA gyrase enzymes to visualize the possible conformation of the compound. Additionally, anticancer activities of target compounds were evaluated on seven different cancer cell lines.Publication Metadata only Novel 4-Thiazolidinones as Non-Nucleoside Inhibitors of Hepatitis C Virus NS5B RNA-Dependent RNA Polymerase(WILEY-V C H VERLAG GMBH, 2015) TATAR, ESRA; Cakir, Gizem; Kucukguzel, Ilkay; Guhamazumder, Rupa; Tatar, Esra; Manvar, Dinesh; Basu, Amartya; Patel, Bhargav A.; Zia, Javairia; Talele, Tanaji T.; Kaushik-Basu, NeerjaIn continuation of our efforts to develop new derivatives as hepatitis C virus (HCV) NS5B inhibitors, we synthesized novel 5-arylidene-4-thiazolidinones. The novel compounds 29-42, together with their synthetic precursors 22-28, were tested for HCV NS5B inhibitory activity; 12 of these compounds displayed IC50 values between 25.3 and 54.1 mu M. Compound 33, an arylidene derivative, was found to be the most active compound in this series with an IC50 value of 25.3 mu M. Molecular docking studies were performed on the thumb pocket-II of NS5B to postulate the binding mode for these compounds.Publication Metadata only Synthesis and Biological Activity of N-(arylsulfonyl) Valine Hydrazones and Assistance of NMR Spectroscopy for Definitive 3D Structure(BENTHAM SCIENCE PUBL LTD, 2019) TATAR, ESRA; Senkardes, Sevil; Tatar, Esra; Nepravishta, Ridvan; Cela, Dorisa; Paci, Maurizio; Ozakpinar, Ozlem Bingol; Sekerler, Turgut; De Clercq, Erik; Pannecouque, Christophe; Kucukguzel, S. Guniz; Kucukguzel, IlkayBackground: Hydrazide-hydrazones constitute an important class of compounds for new drug development. In this study, a series of 39 new acylhydrazones (3-41), derived from (2S)-3-methyl-2-[[( 4-methylphenyl)sulfonyl]amino]butanoic acid hydrazide were synthesized with further aim to achieve biologically active acylhydrazones carrying an amino acid side chain. Methods: Compounds 3-41 were synthesized by microwave-assisted method. All synthesized compounds have been tested for their anti-HIV activity compound 21 was subjected to a new set of 2D-NMR analysis for the characterization of the isomers in solution and determination of its 3D structure. Results: The IC50 values for compounds 2-40 were found between >125-10.90 mu g/ml against HIV-1( IIIB) and HIV-2(ROD) strains in MT-4 cells. Compounds 3, 6, 10, 12, 23, 24, 27, 32, and 37 with CC50 values between 10.90-14.50 mu g/ml were selected to evaluate for their antileukemia activity. IC50 values for these mentioned compounds were found as >100 mu M on human chronic myelogenous leukemia, K562 cell line. Conclusion: Some compounds with IC50 values between 10.90-14.50 mu g/ml will be of benefit in the development of novel leads.Publication Open Access Synthesis, in vitro and in silico studies on novel 3-aryloxymethyl-5-[(2-oxo-2-arylethyl)sulfanyl]-1,2,4-triazoles and their oxime derivatives as potent inhibitors of mPGES-1(2023-01-01) KULABAŞ, NECLA; TATAR, ESRA; KÜÇÜKGÜZEL, İLKAY; BİNGÖL ÖZAKPINAR, ÖZLEM; Erensoy G., Ding K., Zhan C., Çiftçi G., Yelekçi K., Duracık M., Bingöl Özakpınar Ö., Aydemir E., Yılmaz Z. N. , Şahin F., et al.Human microsomal prostaglandin E synthase (mPGES)-1 is a glutathione-dependent membrane-bound enzyme which is involved in the terminal stage of prostaglandin E2 (PGE2) synthesis. It has been well reported as a key target for the discovery of new anti-inflammatory and anti-cancer drugs. Specific inhibitors of mPGES-1 are anticipated to selectively restrain the generation of PGE2 induced by the inflammatory stimuli, without obstructing of the regular biosynthesis of other homeostatic prostanoids. Therefore, the design of mPGES-1 inhibitors can represent a better choice to take control of PGE2 associated diseases, compared with conventional non-steroidal anti-inflammatory drugs and cyclooxygenase (COX) inhibitors, which are known for their serious side effects. Although there is an intensive effort for the identification of mPGES-1 inhibitors, none of the unveiled molecules so far have reached the clinical market. Therefore, the development of novel mPGES-1 inhibitors with proper drug-like properties is still an unmet medical need. As a continuation of our research for the identification of new chemotypes which might inhibit this enzyme, we now report the design and synthesis of 3-aryloxymethyl-5-[(2-oxo2-arylethyl)sulfanyl]-1,2,4-triazoles and their oxime derivatives as inhibitors of human mPGES-1. All synthesized compounds were characterized by FTIR, 1H NMR, 13C NMR (for compounds 12, 14, 15, 26, 27), HMBC (for compounds 6, 7, 8, 16, 19, 23, 28), and MS data. Twenty-four target compounds 7–30 were screened for their mPGES-1/COX-2 inhibitory activities as well as their cytotoxicity. Of these compounds, 20 and 24 showed potent mPGES-1 inhibition by IC50 values of 0.224±0.070 μM and 1.08±0.35 μM, respectively. These two compounds have also been observed to inhibit angiogenesis in matrigel tube formation assay with no toxicity toward HUVEC cells. In silico studies were also held to understand inhibition mechanisms of the most active compounds using molecular docking, molecular dynamics calculations and ADMET predictions.