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Diverse Responses of Neurons and Monocytes to Titanium Dioxide Nanoparticle Exposure
(2019) Engin, Evren Doruk; https://orcid.org/0000-0001-9209-8858; Biyoteknoloji Enstitüsü; Engin, Ayşe Başak
Introduction: The toxicity of titanium dioxide nanoparticles (TiO2NPs) in neurons occurs by glutamate signaling via N-methyl-d-aspartate (NMDA) receptors. Although cellular uptake of TiO2NPs may lead to oxidative stress in macrophages, it is not known whether TiO2NPs have toxic effects on U937 monocytic cell line. Material and Methods: Human neuroblastoma (SH-SY5Y) and U937 human monocytic cell lines were exposed to 25nm and 10nm TiO2NPs, in medium with or without fetal bovine serum (FBS). Mitochondrial metabolic activity was assessed using the MTT-assay before and after treatment with 15 mM N-acetylcysteine (NAC) and 0.1µM or 10µM neopterin. Results: TiO2NPs displayed no toxicity on SH-SY5Y and U937 cells in FBS-free medium. The addition of FBS resulted in a significant reduction in cell viability with both sizes of TiO2NPs on SH-SY5Y and U937 cells. In FBScontaining medium, NAC pretreatment significantly increased cell viability of SH-SY5Y cells in comparison to U937 cells. Both neopterin doses enhanced cell viability of TiO2NPs-exposed SH-SY5Y cells for all concentrations. Only a limited increase in the cell viability was achieved in 10nm TiO2NPs-exposed neurons by pretreatment with neopterin. Whereas, neopterin could not provide a constant amelioration for both 25nm and 10nm sized TiO2NPs-exposed U937 monocytic cells. TiO2NPs displayed size-dependent neuronal toxicity. In FBS-containing medium, both sizes of TiO2NPs caused reduction in cell viability of both cell lines. Conclusion: While toxicity of TiO2NPs emerged via NMDA and AMPA receptors in SH SY5Y cells, U937 cells were most probably activated by AMPA receptors only. Unlike SHSY5Y cells, NADPH oxidase complex inhibition was not effective in TiO2NPs exposed U937 cells.
Optimization of gene expression microarray protocol for formalin-fixed paraffin-embedded tissues
(2016) Özdag, Hilal; http://orcid.org/0000-0001-7940-2499; Biyoteknoloji Enstitüsü; Belder, Nevin; Coşkun, Öznur
Formalin-fixed paraffin-embedded (FFPE) tissue is a widely available clinical specimen for retrospective studies. The possibility of long-term clinical follow-up of FFPE samples makes them a valuable source to evaluate links between molecular and clinical information. Working with FFPE samples in the molecular research area, especially using high-throughput molecular techniques such as microarray gene expression profiling, has come into prominence. Because of the harmful effects of formalin fixation process such as degradation of nucleic acids, cross-linking with proteins, and chemical modifications on DNA and RNA, there are some limitations in gene expression profiling studies using FFPE samples. To date many studies have been conducted to evaluate gene expression profiling using microarrays (Thomas et al., Thomas et al. (2013) [1]; Scicchitano et al., Scicchitano et al. (2006) [2]; Frank et al., Frank et al. (2007) [3]; Fedorowicz et al., Fedorowicz et al. (2009) [4]). However, there is still no generally accepted, efficient and standardized procedure for microarray analysis of FFPE samples. This paper describes the microarray data presented in our recently accepted to be published article showing a standard protocol from deparaffinization of FFPE tissue sections and RNA extraction to microarray gene expression analysis. Here we represent our data in detail, deposited in the gene expression omnibus (GEO) database with the accession number GSE73883. Four combinations of two different cRNA/cDNA preparation and labeling protocols with two different array platforms (Affymetrix Human Genome U133 Plus 2.0 and U133_X3P) were evaluated to determine which combination gives the best percentage of present call. The study presents a dataset for comparative analysis which has a potential in terms of providing a robust protocol for gene expression profiling with FFPE tissue samples.
Hemoglobin alpha 2 gene +861 G>A polymorphism in Turkish population
(2011) Özdag, Hilal; Akar, Nejat; http://orcid.org/0000-0001-7940-2499; Biyoteknoloji Enstitüsü; Dungul, Dilay Ciglidag
Thalassemia is an inherited blood disorder which is divided into two groups: alpha and beta. HBA1 and HBA2 are the two genes associated with alpha thalassemia. The aim of this study is to investigate abnormal hemoglobin variants of alpha globin gene in healthy abnormal hemoglobin carrying individuals with intact beta globin gene. DNA was extracted from peripheral blood samples of seven healthy carrier individuals who have abnormal hemoglobin variants and 16 control individuals from Turkey. Complete coding and intronic sequences of HBA1 and HBA2 genes were amplified by polymerase chain reaction (PCR) and PCR products of HBA1 and HBA2 were sequenced. We were unable to find any base change in our carrier group in the HBA1 gene. We have observed an A/G polymorphism in the downstream untranslated region (+861 G>A) of the HBA2 gene. Our study showed that 14.29% (1/7 carriers) of the carrier group and 37.50% (6/16 controls) of the control group were heterozygous for the +861 G>A polymorphism. The distribution of allele frequencies and genotypes of HBA2 between carrier and control samples were analyzed and it is seen that the distribution of allele frequencies and that of genotypes were not statistically significant between carrier and control samples (P-value = 0.4131, P-value = 0.366, respectively). HBA2 +861 G>A nucleotide substitution is a neutral polymorphism previously reported in other populations. This is the first report in Turkish population.
Genome-Wide Transcriptional Reorganization Associated with Senescence-to-Immortality Switch during Human Hepatocellular Carcinogenesis
(2013) Özdag, Hilal; http://orcid.org/0000-0001-7940-2499; Biyoteknoloji Enstitüsü; Bozkaya, Hakan; İlk, Hakkı Gökhan
Senescence is a permanent proliferation arrest in response to cell stress such as DNA damage. It contributes strongly to tissue aging and serves as a major barrier against tumor development. Most tumor cells are believed to bypass the senescence barrier (become "immortal") by inactivating growth control genes such as TP53 and CDKN2A. They also reactivate telomerase reverse transcriptase. Senescence-to-immortality transition is accompanied by major phenotypic and biochemical changes mediated by genome-wide transcriptional modifications. This appears to happen during hepatocellular carcinoma (HCC) development in patients with liver cirrhosis, however, the accompanying transcriptional changes are virtually unknown. We investigated genome-wide transcriptional changes related to the senescence-to-immortality switch during hepatocellular carcinogenesis. Initially, we performed transcriptome analysis of senescent and immortal clones of Huh7 HCC cell line, and identified genes with significant differential expression to establish a senescence-related gene list. Through the analysis of senescence-related gene expression in different liver tissues we showed that cirrhosis and HCC display expression patterns compatible with senescent and immortal phenotypes, respectively; dysplasia being a transitional state. Gene set enrichment analysis revealed that cirrhosis/senescence-associated genes were preferentially expressed in non-tumor tissues, less malignant tumors, and differentiated or senescent cells. In contrast, HCC/immortality genes were up-regulated in tumor tissues, or more malignant tumors and progenitor cells. In HCC tumors and immortal cells genes involved in DNA repair, cell cycle, telomere extension and branched chain amino acid metabolism were up-regulated, whereas genes involved in cell signaling, as well as in drug, lipid, retinoid and glycolytic metabolism were down-regulated. Based on these distinctive gene expression features we developed a 15-gene hepatocellular immortality signature test that discriminated HCC from cirrhosis with high accuracy. Our findings demonstrate that senescence bypass plays a central role in hepatocellular carcinogenesis engendering systematic changes in the transcription of genes regulating DNA repair, proliferation, differentiation and metabolism.
Differential expression of selected histone modifier genes in human solid cancers
(2006) Özdag, Hilal; http://orcid.org/0000-0001-7940-2499; Biyoteknoloji Enstitüsü; Ahmed, Ahmed Ashour
Background: Post-translational modification of histones resulting in chromatin remodelling plays a key role in the regulation of gene expression. Here we report characteristic patterns of expression of 12 members of 3 classes of chromatin modifier genes in 6 different cancer types: histone acetyltransferases (HATs)- EP300, CREBBP, and PCAF; histone deacetylases (HDACs)- HDAC1, HDAC2, HDAC4, HDAC5, HDAC7A, and SIRT1; and histone methyltransferases (HMTs)- SUV39H1 and SUV39H2. Expression of each gene in 225 samples (135 primary tumours, 47 cancer cell lines, and 43 normal tissues) was analysedby QRT-PCR, normalized with 8 housekeeping genes, and given as a ratio by comparison with a universal reference RNA. Results: This involved a total of 13,000 PCR a ssays allowing for rigorous analysis by fitting a linear regression model to the data. Mutation analysis of HDAC1, HDAC2, SUV39H1, and SUV39H2 revealed only two out of 181 cancer samples (both cell lines) with significant coding-sequence alterations. Supervised analysis and Independent Component Analysis showed that expression of many of these genes was able to discriminate tumour samples from their normal counterparts. Clustering based on the normalized expression ratios of the 12 genes also showed that most samples were grouped according to tissue type. Using a linear discriminant classifier and internal cross-validation revealed that with as few as 5 of the 12 genes, SIRT1, CREBBP, HDAC7A, HDAC5 and PCAF, most samples were correctly assigned. Conclusion: The expression patterns of HATs, HDACs, and HMTs suggest these genes are important in neoplastic transformation and have characteristic patterns of expression depending on tissue of origin, with implications for potential clinical application.
Genome projects 5W1H: What, where, when, why, how and in which population?
(2014) Özdag, Hilal; http://orcid.org/0000-0001-7940-2499; Biyoteknoloji Enstitüsü; Fidanoğlu, Pelin; Belder, Nevin; Erdoğan, Beyza Doğanay
Genome projects aim to decode an organism's complete set of deoxyribonucleic acid (DNA), which can be described as the living code of organism. The idea of the Human Genome Project (HGP) was conceived in the early 1980s. The project was started at 1990 and finished at 2003. The sequencing of the whole human genome derived from the DNA of several anonymous volunteers, costed 3.8 billion dollars. In order to annotate the genome data, the "topography of the genome" and the anatomy of the genes should have been revealed. For this purpose, genome projects of several model organisms was carried out in parallel with HGP with the aim to identify basic structural components, organizational structure and evolutionarily development of the genome. With the advent of microarray technology in the early 2000s, high-throughput screening of Single Nucleotide Polymorphisms (SNPs) and Copy Number Variations (CNVs) became feasible. After the completion of HGP in 13 years, James D. Watson's genome was sequenced with 1 million dollar budget in just 2 months using next generation sequencing technology. Today a human genome can be sequenced in just one day with the cost of 6.600 USD. In this reviev the HGP which created big expectations especially in medicine will be explained from its start to the present. Then we will summarize the studies paving the road to personalized medicine emphasizing the fact that to reveal the meaning of genomic information, it should become computable.
Comparison of high-resolution melting analysis to denaturing high performance liquid chromatography in the detection of point mutations in MEFV, F5, and F2 genes
(2014) Özdag, Hilal; http://orcid.org/0000-0001-7940-2499; Biyoteknoloji Enstitüsü; Sümer Çelebi, Hülya
Background/aim: Sensitive and cost-effective detection of point mutations is important in genetics research. Denaturing highperformance liquid chromatography (DHPLC) is known to be one of the most sensitive techniques for point mutation detection. A more recent technique, high-resolution melting (HRM), is based on the melting behavior of PCR products. In this study, the efficiency and sensitivity of HRM and DHPLC for the detection of MEFV, F5, and F2 gene point mutations were evaluated. Materials and methods: We studied 15 patients with MEFV mutations (E148Q, M680I, M694V, or V726A), 7 patients with the F51691G>A mutation, and 12 patients with the F220210G>A mutation. All mutations were screened by HRM and DHPLC. Results: All mutations were successfully detected by HRM. However, only 4 (MEFV E148Q and M680I, F51691G>A, and F220210G>A) of 6 mutations were successfully detected with DHPLC. Conclusion: Our study showed that HRM is more sensitive than DHPLC for detection of the studied point mutations. © TÜBİTAK.
Protocol for qRT-PCR analysis from formalin fixed paraffin embedded tissue sections from diffuse large b-cell lymphoma: Validation of the six-gene predictor score
(2016) Özdag, Hilal; http://orcid.org/0000-0001-7940-2499; Biyoteknoloji Enstitüsü; Belder, Nevin; Tekin, Nilgün
As a part of an international study on the molecular analysis of Diffuse Large B-cell Lymphoma (DLBCL), a robust protocol for gene expression analysis from RNA extraction to qRT-PCR using Formalin Fixed Paraffin Embedded tissues was developed. Here a study was conducted to define a strategy to validate the previously reported 6-gene (LMO2, BCL6, FN1, CCND2, SCYA3 and BCL2) model as predictor of prognosis in DLBCL. To avoid variation, all samples were tested in a single centre and single platform. This study comprised 8 countries (Brazil, Chile, Hungary, India, Philippines, S. Korea, Thailand and Turkey). Using the Kaplan-Meier and log rank test on patients (n=162) and two mortality risk groups (with those above and below the mean representing high and low risk groups) confirmed that the 6-gene predictor score correlates significantly with overall survival (OS, p < 0.01) but not with event free survival (EFS, p=0.18). Adding the International Prognostic Index (IPI) shows that the 6-gene predictor score correlates significantly with high IPI scores for OS (p < 0.05), whereas those with low IPI scores show a trend not reaching significance (p=0.08). This study defined an effective and economical qRT-PCR strategy and validated the 6-gene score as a predictor of OS in an international setting.
Prospective international cohort study demonstrates inability of interim PET to predict treatment failure in diffuse large B-cell lymphoma
(2014) Özdağ, Hilal; http://orcid.org/0000-0001-7940-2499; Biyoteknoloji Enstitüsü; Kuzu, Işınsu
The International Atomic Energy Agency sponsored a large, multinational, prospective study to further define PET for risk stratification of diffuse large B-cell lymphoma and to test the hypothesis that international biological diversity or diversity of healthcare systems may influence the kinetics of treatment response as assessed by interim PET (I-PET). Methods: Cancer centers in Brazil, Chile, Hungary, India, Italy, the Philippines, South Korea, and Thailand followed a common protocol based on treatment with R-CHOP (cyclophosphamide, hydroxyadriamycin, vincristine, prednisolone with rituximab), with I-PET after 2-3 cycles of chemotherapy and at the end of chemotherapy scored visually. Results: Two-year survivals for all 327 patients (median follow-up, 35 mo) were 79% (95% confidence interval [CI], 74%-83%) for event-free survival (EFS) and 86% (95% CI, 81%-89%) for overall survival (OS). Two hundred ten patients (64%) were I-PET-negative, and 117 (36%) were I-PET-positive. Two-year EFS was 90% (95% CI, 85%-93%) for I-PET-negative and 58% (95% CI, 48%-66%) for I-PET-positive, with a hazard ratio of 5.31 (95% CI, 3.29-8.56). Two-year OS was 93% (95% CI, 88%-96%) for I-PET-negative and 72% (95% CI, 63%-80%) for I-PET-positive, with a hazard ratio of 3.86 (95% CI, 2.12-7.03). On sequential monitoring, 192 of 312 (62%) patients had complete response at both I-PET and end-of-chemotherapy PET, with an EFS of 97% (95% CI, 92%-98%); 110 of these with favorable clinical indicators had an EFS of 98% (95% CI, 92%-100%). In contrast, the 107 I-PET-positive cases segregated into 2 groups: 58 (54%) achieved PET-negative complete remission at the end of chemotherapy (EFS, 86%; 95% CI, 73%-93%); 46% remained PET-positive (EFS, 35%; 95% CI, 22%-48%). Heterogeneity analysis found no significant difference between countries for outcomes stratified by I-PET. Conclusion: This large international cohort delivers 3 novel findings: treatment response assessed by I-PET is comparable across disparate healthcare systems, secondly a negative I-PET findings together with good clinical status identifies a group with an EFS of 98%, and thirdly a single I-PET scan does not differentiate chemoresistant lymphoma from complete response and cannot be used to guide risk-adapted therapy. Copyright © 2014 by the Society of Nuclear Medicine and Molecular Imaging, Inc.
Measurements of inclusive and differential fiducial cross-sectionsoft ̄tγproduction in leptonic final states at√s=13 TeV in ATLAS
(2019) Çakır, Orhan; Duran Yıldız, Hatice; Fen Fakültesi
Inclusive and differential cross-sections for the production of a top-quark pair in association with a photon are measured with proton-proton collision data corresponding to an integrated luminosity of 36.1 fb-1, collected by the ATLAS detector at the LHC in 2015 and 2016 at a centre-of-mass energy of 13 TeV. The measurements are performed in single-lepton and dilepton final states in a fiducial volume. Events with exactly one photon, one or two leptons, a channel-dependent minimum number of jets, and at least one b-jet are selected. Neural network algorithms are used to separate the signal from the backgrounds. The fiducial cross-sections are measured to be 521±9(stat.)±41(sys.)fb and 69±3(stat.)±4(sys.)fb for the single-lepton and dilepton channels, respectively. The differential cross-sections are measured as a function of photon transverse momentum, photon absolute pseudorapidity, and angular distance between the photon and its closest lepton in both channels, as well as azimuthal opening angle and absolute pseudorapidity difference between the two leptons in the dilepton channel. All measurements are in agreement with the theoretical predictions.
Performance of top-quark andW-boson tagging with ATLAS inRun 2 of the LHC
(2019) Çakır, Orhan; Duran Yıldız, Hatice; Fen Fakültesi
The performance of identification algorithms (“taggers”) for hadronically decaying top quarks and W bosons in pp collisions at s = 13 TeV recorded by the ATLAS experiment at the Large Hadron Collider is presented. A set of techniques based on jet shape observables are studied to determine a set of optimal cut-based taggers for use in physics analyses. The studies are extended to assess the utility of combinations of substructure observables as a multivariate tagger using boosted decision trees or deep neural networks in comparison with taggers based on two-variable combinations. In addition, for highly boosted top-quark tagging, a deep neural network based on jet constituent inputs as well as a re-optimisation of the shower deconstruction technique is presented. The performance of these taggers is studied in data collected during 2015 and 2016 corresponding to 36.1 fb - 1 for the tt¯ and γ+ jet and 36.7 fb - 1 for the dijet event topologies.
Searches for third-generation scalar leptoquarks inps= 13TeVppcollisions with the ATLAS detector
(2019) Çakır, Orhan; Duran Yıldız, Hatice; Fen Fakültesi
Limits are set on the pair production of scalar leptoquarks, where all possible decays of the leptoquark into a quark (t, b) and a lepton (τ, ν) of the third generation are considered. The limits are presented as a function of the leptoquark mass and the branching ratio into charged leptons for up-type (LQ3 u → tν/bτ) and down-type (LQ3 d → bν/tτ) leptoquarks. Many results are reinterpretations of previously published ATLAS searches. In all cases, LHC proton-proton collision data at a centre-of-mass energy of s = 13 TeV recorded by the ATLAS detector in 2015 and 2016 are used, corresponding to an integrated luminosity of 36.1 fb−1. Masses below 800 GeV are excluded for both LQ3 u and LQ3 d independently of the branching ratio, with masses below about 1 TeV being excluded for the limiting cases of branching ratios equal to zero or unity.[Figure not available: see fulltext.].
Measurement ofW±Zproduction cross sections and gauge bosonpolarisation inppcollisions at√s=13 TeV with the ATLASdetector
(2019) Çakır, Orhan; Duran Yıldız, Hatice; Fen Fakültesi
This paper presents measurements of W±Z production cross sections in pp collisions at a centre-of-mass energy of 13 TeV. The data were collected in 2015 and 2016 by the ATLAS experiment at the Large Hadron Collider, and correspond to an integrated luminosity of 36.1fb-1. The W±Z candidate events are reconstructed using leptonic decay modes of the gauge bosons into electrons and muons. The measured inclusive cross section in the detector fiducial region for a single leptonic decay mode is σW±Z→ℓ′νℓℓfid.=63.7±1.0(stat.)±2.3(syst.)±1.4(lumi.) fb, reproduced by the next-to-next-to-leading-order Standard Model prediction of 61.5-1.3+1.4 fb. Cross sections for W+Z and W-Z production and their ratio are presented as well as differential cross sections for several kinematic observables. An analysis of angular distributions of leptons from decays of W and Z bosons is performed for the first time in pair-produced events in hadronic collisions, and integrated helicity fractions in the detector fiducial region are measured for the W and Z bosons separately. Of particular interest, the longitudinal helicity fraction of pair-produced vector bosons is also measured.
Observation of electroweak W±Zboson pair production in association with two jets in ppcollisions at √s=13 TeV with the ATLAS detector
(2019) Çakır, Orhan; Duran Yıldız, Hatice; Fen Fakültesi
An observation of electroweak W±Z production in association with two jets in proton–proton collisions is presented. The data collected by the ATLAS detector at the Large Hadron Collider in 2015 and 2016 at a centre-of-mass energy of s=13 TeV are used, corresponding to an integrated luminosity of 36.1fb−1. Events containing three identified leptons, either electrons or muons, and two jets are selected. The electroweak production of W±Z bosons in association with two jets is measured with an observed significance of 5.3 standard deviations. A fiducial cross-section for electroweak production including interference effects and for a single leptonic decay mode is measured to be σWZjj−EW=0.57−0.13 +0.14(stat.)−0.06 +0.07(syst.)fb. Total and differential fiducial cross-sections of the sum of W±Zjj electroweak and strong productions for several kinematic observables are also measured.
Investigation of the synthesis of some dehydroalanine derivatives
(2000) Süzen, Sibel; Eczacılık Fakültesi; Williams, John Michael
Dehydroamino acids represent an important class of compound as they are key intermediates in unusual amino acid and in the design of peptides and are constituents of a variety of naturally occurring antibiotic and phytotoxic peptides. In view of the importance of proteins and peptides containing hydroxyamino acids and the problems associated with their synthesis and dehydration, an investigation was performed on model compounds in order to examine the difficulties of the dehydration reactions. The preparation and properties of the model dehydroalanine derivatives have been studied.
Rat lung aldose reductase inhibition capacity of substituted indole hydrazide/hydrazone derivatives
(2012) Süzen, Sibel; Eczacılık Fakültesi; Daş Evcimen, Net; Sarikaya, Mutlu; Karaaslan, Cigdem; Yilmaz, Ayşe Didem; Shirinzadeh, Hanif
Diabetes Mellitus is one of the most serious health problem facing both developed and developing countries. Long term complications lead to morbidity and mortality in patients with diabetes. Increased polyol pathway has been implicated in the pathogenesis of microvascular complications and cataract. Aldose reductase (AR) is the key enzyme of the polyol pathway, which converts glucose to sorbitol. Excessive accumulation of sorbitol is associated to the diabetic complications. Avoidance of sorbitol accumulation by inhibiting AR would be an efficient treatment. Due to the significance of AR as a potential drug target in the treatment of diabetic complications, there are increasing interests in the design and synthesis of AR inhibitors. In this study, 2-fluorophenylindol and 5-chloroindole hydrazide/hydrazone derivatives were tested for measuring the AR enzyme inhibitory activity. The enzyme activity was assayed by spectrophotometrically monitoring NADPH oxidation, which accompanies the reduction of D,L-glyceraldehyde used as substrate. Results showed in general 52-60 % inhibitory activity in halogen substituted indole derivatives. This study proposes a new approach for the in vitro AR inhibition activity properties and structure activity relationship of 2, 3-and 5-substituted indole ring. For the inhibitory activity, not only the indole ring is important, but also is the side chain containing the amide group and halogens.
Synthesis and antioxidant activity evaluations of melatonin-based analogue indole-hydrazide/hydrazone derivatives
(2012) Süzen, Sibel; Eczacılık Fakültesi; Yilmaz, Ayşe Didem; Çoban, Tülay
Melatonin (MLT) is a hormone synthesized from the pineal gland. It is a direct scavenger of free radicals, which is related to its capability to defend cells from oxidative stress. Recently MLT-related compounds are under investigation to establish which exhibit the maximum activity with the lowest side effects. In this study 5-chloroindole hydrazide/hydrazone derivatives were synthesized from 5-chloroindole-3-carboxaldehyde and phenyl hydrazine derivatives. All the compounds characterized and in vitro antioxidant activity was investigated against MLT and BHT. Most of the compounds showed strong inhibitory effect on the superoxide radical scavenging assay at 1mM concentration (79 to 95%). Almost all the tested compounds possessed strong scavenging activity against the DPPH radical scavenging activity with IC 50 values (2 to 60 μM). Lastly, compound 1j revealed stronger inhibitory activity against MLT in the LP inhibitory assay at 0.1mM concentration (51%) while the rest of the compounds showed moderate inhibition. © 2012 Informa UK, Ltd.
Antimicrobial evaluation of indole-containing hydrazone derivatives
(2011) Süzen, Sibel; Eczacılık Fakültesi; Shirinzadeh, Hanif; Altanlar, Nurten; Yücel, Nihal; Özden, Seçkin
There has been an increasing importance of drug-resistant pathogens in clinical microbiological and antibacterial research. Indoles and hydrazone-type compounds constitute important classes of compounds in the search for effective agents against multidrug-resistant microbial infections. In this study a series of 1-methylindole-3-carboxaldehyde hydrazone derivatives were evaluated for their in vitro antimicrobial activities using the two-fold serial dilution technique against Staphylococcus aureus, methicillin-resistant S. aureus, methicillin-resistant S. aureus isolate, Escherichia coli, Bacillus subtilis, and Candida albicans. The minimum inhibitory concentration (MIC) of the test compounds and the reference standards sultamicillin, ampicillin, fl uconazole, and ciprofl oxacin was determined. All compounds possessed a broad spectrum of activity having MIC values of 6.25-100 μg/ml against the tested microorganisms. Aromaticity and disubstitution of the phenyl ring with especially fl uorine and chlorine atoms were found to be signifi cant for the antimicrobial activity. © Verlag der Zeitschrift für Naturforschung, Tübingen.
Evaluation of rat kidney aldose reductase inhibitory activity of some N-acetyl dehydroalanine derivatives
(2011) Süzen, Sibel; Eczacılık Fakültesi; Daş Evci̇Men, Net; Sarikaya, Mutlu; Gürkök, Gökce
Aldose reductase (AR) is an enzyme that catalyzes the conversion of glucose to sorbitol, which is in turn converted to fructose by sorbitol dehydrogenase. Increased AR activity has been implicated in the pathogenesis of diabetic complications such as neuropathy, nephropathy, retinopathy, and cataract. Inhibitors of AR thus seem to have the potential to prevent or treat diabetic complications. At present, however, side effects and/or insufficient pharmacokinetic profiles have made most of the drug candidates undesirable. In this study, the synthesis (l-o) and ARI activity of 15 N-acetyl dehydroalanine derivatives (a-o) are described. The synthesized compounds mainly contained aliphatic and aromatic side chains. The insertion of ethyl and chloro propyl side chains were shown to be more effective than the rest of the compounds. Between the synthesized compounds N-ethyl (b) and N-propylchloride (h) derivatives showed the best ARI activities. © 2011 Springer Science+Business Media, LLC.
Melatonin analogue new indole hydrazide/hydrazone derivatives with antioxidant behavior: Synthesis and structureactivity relationships
(2009) Süzen, Sibel; Dil ve Tarih-Coğrafya Fakültesi; Gürkök, Gökce; Çoban, Tülay
Melatonin (MLT) is a hormone produced in the brain by the pineal gland, from the amino acid tryptophan. It is also an antioxidant hormone with a particular role in the protection of nuclear and mitochondrial DNA. In recent years, many physiological properties of MLT have been described resulting in much attention in the development of synthetic compounds possessing the indole ring. Sixteen MLT analogue indole hydrazide/hydrazone derivatives were synthesized and in vitro antioxidant activity was investigated. Most of the compounds showed significantly higher activity than MLT at 10- 3 M and 10- 4 M concentrations

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