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TATAR, ESRA

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TATAR

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ESRA

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Now showing 1 - 8 of 8
  • PublicationOpen 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
    Synthesis of some novel heterocyclic compounds derived from diflunisal hydrazide as potential anti-infective and anti-inflammatory agents
    (ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER, 2007) TATAR, ESRA; Kucukguzel, S. Gueniz; Tatar, Esra; Rollas, Sevim; Sahin, Fikrettin; Gulluce, Medine; De Clercq, Erik; Kabasakal, Levent
    Three novel series of 2',4'-difluoro-4-hydroxybiphenyl-3-carboxylic acid derivatives namely 4-substituted-1,2,4-triazoline-3-thiones (4a-g); 2-substituted- 1.3.4-thiadiazoles (5a-g) and 2-substituted- 1,3,4-oxadiazoles (6a-g) have been synthesized. Twenty-one of the newly synthesized compounds were tested against various bacteria, fungi, yeast species and virus. In addition, we have replaced the carboxylic acid group of diflunisal with heterocycles and the anti-inflammatory activity of heterocycles reported here. Compound (5d) showed activity against Escherichia coli Al and Streptococcuspyogenes ATCC-176 at a concentration of 31.25 mu g/mL, whereas cefepime, the drug used as standard, has been found less active against the bacteria mentioned above. Compound (4b) has exhibited activity against Aspergillus variecolor and Trichophyton rubrum at a concentration of 31.25 and 15.25 mu g/mL, whereas Amphotericin B, the drug used as standard, has been found less active against the yeast and fungi. The highest antiviral activity was found in the 1,3,4-thiadiazole derivative (5a) having a methyl group at 2nd position against Sindbis virus at 9.6 mu g/mL. Compound (4c) exhibited the highest anti-inflammatory activity (73.03%) whereas diflunisal, the drug used as standard, has been found less active (24.16%). Compound (5f) presented similar antinociceptive activity with the standard drug (paw withdrawal latency was 19.21 s compared to that of diflunisal which was 19.14 s, in hot plate test). (c) 2007 Elsevier Masson SAS. All fights reserved.
  • Publication
    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, Neerja
    In 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
    Some Hydrazones of 2-Aroylamino-3-methylbutanohydrazide: Synthesis, Molecular Modeling Studies, and Identification as Stereoselective Inhibitors of HIV-1
    (WILEY-V C H VERLAG GMBH, 2013) TATAR, ESRA; Tatar, Esra; Kucukguzel, Ilkay; Daelemans, Dirk; Talele, Tanaji T.; Kaushik-Basu, Neerja; De Clercq, Erik; Pannecouque, Christophe
    In accordance with our antiviral drug development attempt, acylhydrazone derivatives bearing amino acid side chains were synthesized for the evaluation of their antiviral activity against various types of viruses. Among these compounds, 8S, 11S, and 12S showed anti-HIV-1 activity with a 50% inhibitory concentration (IC50)=123.8 mu M (selectivity index, SI>3), IC50=12.1 mu M (SI>29), IC50=17.4 mu M (SI>19), respectively. Enantiomers 8R, 11R, and 12R were inactive against the HIV-1 strain IIIB. Hydrazones 8S, 11S, and 12S which were active against HIV-1 wild type showed no inhibition against a double mutant NNRTI-resistant strain (K103N;Y181C). Molecular docking calculations of R- and S-enantiomers of 8, 11, and 12 were performed using the hydrazone-bound novel site of HIV-1 RT.
  • PublicationOpen Access
    2-Heteroarylimino-5-arylidene-4-thiazolidinones as a new class of non-nucleoside inhibitors of HCV NS5B polymerase
    (ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER, 2013-11) TATAR, ESRA; Kucukguzel, Ilkay; Satilmis, Gokhan; Gurukumar, K. R.; Basu, Amartya; Tatar, Esra; Nichols, Daniel B.; Talele, Tanaji T.; Kaushik-Basu, Neerja
    Hepatitis C virus (HCV) NS5B polymerase is an important and attractive target for the development of anti-HCV drugs. Here we report on the design, synthesis and evaluation of twenty-four novel allosteric inhibitors bearing the 4-thiazolidinone scaffold as inhibitors of HCV NS5B polymerase. Eleven compounds tested were found to inhibit HCV NS5B with IC50 values ranging between 19.8 and 64.9 RM. Compound 24 was the most active of this series with an IC50 of 5.6 mu M. A number of these derivatives further exhibited strong inhibition against HCV lb and 2a genotypes in cell based antiviral assays. Molecular docking analysis predicted that the thiazolidinone derivatives bind to the NS5B thumb pocketII (TP-II). Our results suggest that further optimization of the thiazolidinone scaffold may be possible to yield new derivatives with improved enzyme- and cell-based activity. (C) 2013 Elsevier Masson SAS. All rights reserved.
  • PublicationOpen Access
    Synthesis, characterization and biological evaluation of 1,3-thiazolidine-4-ones derived from (2S)-2-benzoylamino-3-methylbutanohydrazide hydrazones
    (MARMARA UNIV, 2021) TATAR, ESRA; Tatar, Esra; Kucukguzel, Ilkay; Otuk, Gulten; Bilgin, Merve; De Clercq, Erik; Andrei, Graciela; Snoeck, Robert; Pannecouque, Christophe; Kaushik-Basu, Neerja
    Novel 2-aryl-5-non-substituted / methyl-1,3-thiazolidine-4-one derivatives 14-33 carrying L-valine core were synthesized by the reaction of acylhydrazones 4-13 with thioglycolic acid / thiolactic acid. Structures of all synthesized compounds 14-33 were confirmed by IR, H-1-NMR and HR-MS analysis and C-13-NMR were recorded for selected compounds 17, 21, 28 and 30. None of the compounds 14-33 showed activity against HIV-1 (strain IIIB) or HIV-2 (strain ROD) in an MT-4/MTT based assay. Compounds 14-33 were also screened against Feline Corona Virus (FIPV), Feline Herpes Virus, HSV-1(KOS), HSV-1 (TK-KOS ACVr), HSV-2 (G), Vaccinia virus, Vesicular stomatitis virus, Cytomegalovirus, Varicella-Zoster virus, Respiratory syncytial virus, Coxsackie B4 virus, Parainfluenza-3 virus, Reovirus-1, Sindbis virus and Punta Toro virus, but none of them showed antiviral activity at subtoxic concentrations. Anti-HCV NS5B RdRp activity of some selected compounds from the series 14-33 were found to vary between 4.1-27 % at the concentration of 100 mu M. In vitro antibacterial activity evaluation of selected compounds 16-23 and 25-32, against Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Enterococcus faecalis ATCC 29212, Klebsiella pneumoniae ATCC 4352, Bacillus subtilis ATCC 6633, Staphylococcus epidermidis ATCC 12228, MRSA and antifungal activity against Candida albicans ATCC 10231 resulted in the MIC values between 625->5000 mu g/ml.
  • Publication
    Synthesis and structure-activity relationship of L-methionine-coupled 1,3,4-thiadiazole derivatives with activity against influenza virus
    (WILEY) TATAR, ESRA; Tatar, Esra; Yaldiz, Seda; Kulabas, Necla; Vanderlinden, Evelien; Naesens, Lieve; Kucukguzel, Ilkay
    In previous investigations, we identified a class of 1,3,4-thiadiazole derivatives with antiviral activity. N-{3-(Methylsulfanyl)-1-[5-(phenylamino)-1,3,4-thiadiazole-2-yl]propyl}benzamide emerged as a relevant lead compound for designing novel influenza A virus inhibitors. In the present study, we elaborated on this initial lead by performing chemical synthesis and antiviral evaluation of a series of structural analogues. During this research, thirteen novel 1,3,4-thiadiazole derivatives were synthesized by the cyclization of the corresponding thiosemicarbazides as synthetic precursors. The structures and the purities of the synthesized compounds were confirmed through chromatographic and spectral data. Four L-methionine-based 1,3,4-thiadiazole derivatives displayed activity against influenza A virus, the two best compounds being 24 carrying a 5-(4-chlorophenylamino)-1,3,4-thiadiazole moiety and 30 possessing a 5-(benzoylamino)-1,3,4-thiadiazole structure [antiviral EC50 against influenza A/H3N2 virus: 4.8 and 7.4 mu M, respectively]. The 1,3,4-thiadiazole derivatives were inactive against influenza B virus and a wide panel of unrelated DNA and RNA viruses. Compound 24 represents a new class of selective influenza A virus inhibitors acting during the virus entry process, as evidenced by our findings in a time-of-addition assay. Molecular descriptors and in silico prediction of ADMET properties of the active compounds were calculated. According to in silico ADMET and drug similarity studies, active compounds have been estimated to be good candidates for oral administration with no apparent toxicity considerations.
  • Publication
    Synthesis of some novel thiourea derivatives obtained from 5-[4-aminophenoxy)methyl]-4-alkyl/aryl-2,4-dihydro-3H-1,2,4-triazole-3-thiones and evaluation as antiviral/anti-HIV and anti-tuberculosis agents
    (ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER, 2008) TATAR, ESRA; Kucukguzel, Ilkay; Tatar, Esra; Kucukguzel, S. Guniz; Rollas, Sevim; De Clercq, Erik
    As a continuation of our previous efforts on N-alkyl/aryl-N'-[4-(4-alkyl/aryl-2,4-dihydro-3H-1,2,4-triazole-3-thione-5-yl)phenyl]thioureas 1-19 and N-alkyl/aryl-N'-[4-(3-aralkylthio-4-alkyl/aryl-4H-1,2,4-triazole-5-yl)phenyl]thioureas 20-22, a series of novel 5-[(4-aminophenoxy)-methyl] -4- alkyl/aryl-2,4-dihydro-3H-1,2,4-triazole-3-thiones 23-26 and several related thioureas, N-alky/aryl-N'-{4-[(4-alkyl/aryl-5-thioxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)methoxy]phenyl)thioureas 27-42 were synthesized for evaluation of their antiviral potency. Structures of the synthesized compounds were confirmed by the use of H-1 NMR, C-13 NMR and HR-MS data. All compounds 1-42 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 HeLa, Vero, HEL and E 6SM cell cultures, and anti-tuberculosis activity against Mycobacterium tuberculosis H37Rv. Compounds 4 and 5 showed weak activity against HSV-1, HSV-2 and TK- HSV, whereas eight compounds showed marginal activity against Coxsackie virus B4. The most active derivative in this series was compound 38 which showed moderate protection against Coxsackie virus B4 with an MIC value of 16 mu g/ml and a selectivity index of 5. This compound was also active against thymidine kinase positive Varicella-zoster virus (TK+ VZV, OKA strain) with an EC50 value of 9.9 mu g/ml. Compound 38 was the most active compound with 79% inhibition against M. tuberculosis H37Rv. (c) 2007 Elsevier Masson SAS. All rights reserved.