Person: KÜÇÜKGÜZEL, İLKAY
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KÜÇÜKGÜZEL
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İLKAY
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Publication Metadata only Novel fluoroquinolones containing 2-arylamino-2-oxoethyl fragment: Design, synthesis, evaluation of antibacterial and antituberculosis activities and molecular modeling studies(WILEY, 2022) TÜRE, ASLI; Kulabas, Necla; Ture, Asli; Bozdeveci, Arif; Krishna, Vagolu Siva; Karaoglu, Sengul Alpay; Sriram, Dharmarajan; Kucukguzel, IlkayNovel substituted fluoroquinolone derivatives, compounds 6-20 were designed, synthesized, and evaluated for antituberculosis and antibacterial activity. Antibacterial activities of the compounds were determined and compound 14 was found to be the most potent antimicrobial agent owing to minimal inhibitory concentration (MIC) value of <1.16 mu g/mu l for all tested bacteria. Further, compounds were tested in vitro for their antimycobacterial activity against Mycobacterium tuberculosis H37Rv. Most of the compounds showed antimycobacterial effects with 1.56-25.00 mu g/ml MIC values. Compounds 14 and 18 were found to be the most active derivatives due to their MIC at 1.56 mu g/ml. Selected compounds 11, 14, 17, and 18 were tested for M. tuberculosis DNA supercoiling assay and they had IC50 values within a range of 6.35-15 mu M. Mechanism of binding to DNA gyrase enzymes was evaluated using in silico molecular modeling studies and it was shown that compounds 6-20 adopt a similar binding mode as already known for fluoroquinolone drugs.Publication Metadata only Synthesis, antiviral and anticancer activity of some novel thioureas derived from N-(4-nitro-2-phenoxyphenyl)-methanesulfonamide(ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER, 2009) KÜÇÜKGÜZEL, İLKAY; Karakus, Sevgi; Kucukguzel, S. Guniz; Kucukguzel, Ilkay; De Clercq, Erik; Pannecouque, Christophe; Andrei, Graciela; Snoeck, Robert; Sahin, Fikrettin; Bayrak, Oemer FarukDue to a continuing effort to develop new antiviral agents, a series of 1-[4-(methanesulfonamido)-3-phenoxyphenyl]-3-alkyl/aryl thioureas 3a-i have been synthesized by the reaction of alkyl/aryl isothiocyanates with 4-amino-2-phenoxymethanesulfonanilide. These derivatives were structurally characterized by the use of spectral techniques and evaluated for their anticancer and antiviral activities. None of the tested compounds showed significant anticancer properties on A549 and L929 cell lines. All synthesized compounds 3a-i were evaluated in vitro against HIV-1 (IIIB) and HIV-2 (ROD) strains in MT-4 cells, as well as other selected viruses such as HSV-1, HSV-2, Coxsackie virus B4, Sindbis virus and varicella-zoster virus using HEL, HeLa and Vero cell cultures. Compound 3b was able to block HIV replication with almost 100% maximum protection at 125 mu g/ml, and IC50 values of 54.9 mu g/ml and 65.9 mu g/ml against HIV-1 and HIV-2, respectively. (C) 2009 Elsevier Masson SAS. All rights reserved.Publication Open Access Evaluation of molnupiravir analogues as novel coronavirus (SARS-CoV-2) RNA-dependent RNA polymerase (RdRp) inhibitors - an in silico docking and ADMET simulation study(MARMARA UNIV, 2021) KÜÇÜKGÜZEL, İLKAY; Kulabas, Necla; Yesil, Tugce; Kucukguzel, IlkayThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is characterized by a wide range of symptoms including fever, dry cough, headache, decreased sense of taste and smell, was first identified in Wuhan, China in December 2019. Currently, the nucleoside analog, remdesivir has been approved for emergency use authorization (EUA) by the regulatory agencies for the treatment of COVID-19 patients. The need for new antiviral agents has been continuing due to the some disadvantages of remdesivir. Molnupiravir (MLN) that is developed for the treatment of hepatitis C virus (HCV), have been reported to show antiviral activity against SARS-CoV-2 according to the results of a high throughput screen of nucleoside analogs and also phase II/III clinical trials of MLN is ongoing. In this study, fifty four MLN analogs (twelve of them are found to be reported in the literature whereas forty two of them are novel molecules) against SARS-CoV-2 RdRp were designed and evaluated for their potential antiviral activity by using molecular modelling studies. While among the designed MLN analogs, compound C17 was found to have the best potential inhibitor with-7.3 kcal/mol binding energy that is higher than molnupiravir and its active form EIDD-1931. Therefore, the isobutyric acid ester and monophosphate forms of C17 were also compared to the related MLN derivatives in terms of active site interactions. Lastly, the ten compounds with the best binding affinity including C17 were tested in silico for bioavailability, drug-likeness, ADME and safety profiles and were found to exhibit similar bioavailability and safety profile to MLN.Publication Metadata only Synthesis, molecular docking and evaluation of novel sulfonyl hydrazones as anticancer agents and COX-2 inhibitors(SPRINGER, 2020) KÜÇÜKGÜZEL, İLKAY; Senkardes, Sevil; Han, M. Ihsan; Kulabas, Necla; Abbak, Muruvvet; Cevik, Ozge; Kucukguzel, Ilkay; Kucukguzel, S. GunizIn trying to develop new anticancer agents, a series of sulfonylhydrazones were synthesized. All synthesized compounds were checked for identity and purity using elemental analysis, TLC and HPLC and were characterized by their melting points, FT-IR and NMR spectral data. All synthesized compounds were evaluated for their cytotoxic activity against prostate cancer (PC3), breast cancer (MCF-7) and L929 mouse fibroblast cell lines. Among them,N '-[(2-chloro-3-methoxyphenyl)methylidene]-4-methylbenzenesulfonohydrazide(3k)showed the most potent anticancer activity against both cancer cells with good selectivity (IC50 = 1.38 mu M on PC3 with SI = 432.30 and IC50 = 46.09 mu M on MCF-7 with SI = 12.94). Further investigation confirmed that3kdisplayed morphological alterations in PC3 and MCF-7 cells and promoted apoptosis through down-regulation of the Bcl-2 and upregulation of Bax expression. Additionally, compound3kwas identified as the most potent COX-2 inhibitor (91% inhibition) beside lower COX-1 inhibition. Molecular docking of the tested compounds represented important binding modes which may be responsible for their anticancer activity via inhibition of the COX-2 enzyme. Overall, the lead compound3kdeserves further development as a potential anticancer agent. [GRAPHICS] .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 evaluation of antiviral, antitubercular and anticancer activities of some novel thioureas derived from 4-aminobenzohydrazide hydrazones [4-Aminobenzohidrazit hidrazonlarından türetilmiş bazı yeni tiyoürelerin sentezi, antiviral, antitüberküler ve antikanser etkilerinin deǧerlendirilmesi](Marmara University, 2010) KÜÇÜKGÜZEL, İLKAY; Çikla P., Güniz Küçükgüzel Ş., Küçükgüzel I., Rollas S., De Clercq E., Pannecouque C., Andrei G., Snoeck R., Şahin F., Bayrak Ö.F.A series of novel 1-[4-[[2-[(4-substituted phenyl)methylene]hydrazino]carbonyl]p henyl]-3-substituted thiourea derivatives have been synthesized by the addition of substituted aryl isothiocyanates to 4-amino-N'-[(4-substituted phenyl) methylene] benzohydrazide, which was prepared by condensation of 4-aminobenzoic acid hydrazide with 4-fluorobenzaldehyde or 4-(trifluoromethyl)benzaldeyde. All synthesized compounds were evaluated in vitro against HIV-1 (IIIB) and HIV-2 (ROD) strains in MT-4 cells, as well as other selected viruses such as HSV-1, HSV-2, Coxsackie virus B4, Sindbis virus, human cytomegalovirus, and varicella-zoster virus using HeLa, Vero, or HEL cell cultures. Antimycobacterial activity against Mycobacterium tuberculosis H37 Rv was also evaluated. The anticancer activity and cytotoxicity screening of the synthesized compounds were determined on A 549 and L 929 cell lines.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 Molecular modeling and assessment of cytotoxic and apoptotic potentials of imatinib analogues featuring (thio)urea motifs in human leukemia and lymphoma cells(MARMARA UNIV, 2020) TÜRE, ASLI; Bingol Ozakpinar, Ozlem; Ture, Asli; Kucukguzel, IlkayImatinib is a well-known anticancer drug. In this study, cytotoxic properties of thirty-two imatinib analogues featuring (thio)urea motifs have been evaluated against chronic myeloid leukemia (K562), Burkitt lymphoma (Raji) and mouse embryonic fibroblast (NIH 3T3) cells. IC50 values of selected eleven compounds were calculated against K562 and NIH 3T3 cells. Apoptotic properties of the most active three compounds were evaluated on K652 cells subsequently. Favorably, compounds 19, 31 and 32 induced early apoptotic changes on K562 cells. Loss of membrane potential as well as caspase-3 and caspase-9 activation was determined in the present study. Levels of anti-apoptotic proteins, Bcl-XL and Bcl-2 decreased after the implementation of compounds 19, 31 and 32 at 10 mu M and 50 mu M concentrations. To reveal further molecular insight into the anticancer activity of the compounds, compounds 19, 31 and 32 were docked into ABL kinase protein as imatinib shows anticancer activity by inhibiting this enzyme. Modeling studies demonstrated significant molecular interactions between compounds 19, 31 and 32 and ABL protein. Compounds 19, 31 and 32 showed excellent superposition with imatinib in the binding site of ABL. These findings suggest that compounds 19, 31 and 32 have potential to show anticancer activity against chronic myeloid leukemia.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.