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PubMed | Agr Ibrahim Cecen University, Balikesir University, Ondokuz Mayis University, Agri Ibrahim Cecen University and 3 more.
Type: Journal Article | Journal: Bioorganic & medicinal chemistry letters | Year: 2015

A series of hydrazinecarbothioamide derivatives incorporating ethyl, phenyl, tolyl, benzyl, and allyl moieties were prepared and tested as possible inhibitors of three members of the pH regulatory enzyme family, carbonic anhydrase (CA; EC 4.2.1.1). The inhibitory and activatory potencies of the compounds against the cytosolic human isoforms hCA I and hCA II and the transmembrane, tumor-associated hCA IX were analyzed by a hydrase assay with CO2 as substrate, and the inhibition constants (KI) were calculated. Most compounds investigated here exhibited nanomolar or low micromolar inhibition constants against the three isoenzymes. KI values were in the range of 34.1-871 nM for hCA I and compounds 5-10 showed interesting activation of the hCA II with KA value of 0.81-12.5 M. Compounds 11-16 exhibited moderate inhibition effects on hCA IX in the range of 0.317-1.245 M but they were less effective for hCA II. Tested compounds were also investigated using in silico applications at the binding pockets of these three targets. The different mechanisms of inhibition by these tested compounds as compared to sulfonamides, and their diverse inhibition profile for these mammalian isozymes, makes this class of derivatives of great interest for the design of novel CA inhibitors.


Yerlikaya E.,Siirt State University | Erdogan O.,Atatürk University | Demirdag R.,Agr Ibrahim Cecen University | Senturk M.,Agr Ibrahim Cecen University | Kufrevioglu O.I.,Atatürk University
Turkish Journal of Biochemistry | Year: 2015

Objective: In this study, investigating the effects of inhibition of the enzyme activity of some antitumor drugs and the Cancer-Related Human Carbonic Anhydrase IX (hCA IX) isoenzyme expressing as a SUMO fusion protein in an Escherichia coli expression system were aimed. Methods: hCA IX isoenzyme was expressed using SUMO fusion technology. The fusion protein was expressed ina totally soluble form and the expression was verified by SDS-PAGE analysis. Affinity chromatography was used in the purification processes. The effects of certain antitumor drugs on enzyme activity were investigated in vitro conditions by using esterase activity. IC50 values of drugs showing the inhibitory effect were calculated. Inhibition types and Ki values for antitumor drugs, which inhibit the enzyme, were determined by separately plotting Lineweaver Burk plots. Results: The molecular weight of the fusion protein was approximately 85kDa. The optimal induction concentration of IPTG and the growth temperature were found to be1.0mM and 30oC. The fusion protein was purified at approximately 3.07-fold with a yield of 92.58%, and a specific activity of 43707EU/mg proteins by nickel nitrilo-triacetic acid resin chromatography. Conclusion: Our work is extremely important because CA IX plays a clinical role as a biomarker in cancer diagnosis and the use of specific inhibitors of the CA IX enzyme will be useful in the fight against cancer. In vitro inhibition studies on the recombinant hCA IX enzyme can shed light on the development of anticancer drugs for cancers overexpressing CA IX. © 2015. Turkish Biochemistry Society. All rights reserved.


PubMed | Agr Ibrahim Cecen University, Kafkas University, Erzincan University, Siirt State University and Atatürk University
Type: Journal Article | Journal: Journal of enzyme inhibition and medicinal chemistry | Year: 2016

This study was designed to investigate the antioxidant effects of Naringin, in ischemia/reperfusion (I/R)-induced skeletal muscle injury in rats. The rats were randomly allocated into three groups including control, I/R and I/R+Naringin groups. Muscle tissues of I/R groups revealed significantly higher antioxidant enzyme activities, and increased levels of malondialdehyde, as specific a marker of the lipid peroxidation and tissue damage, compared to the control group (p<0.05). Levels of these parameters in muscle revealed significant reductions in the I/R+Naringin group compared to the I/R group (p<0.05). Histopathological examination of ischemia muscles in the I/R group showed significant degeneration and inflammation compared to the control group, whereas ischemic muscles of Naringin-administered group showed significant reduction in degeneration and inflammation compared to the I/R group (p<0.05). We suggest that the protective effect of Naringin may reduce the I/R injury in cases of extremity injuries with acute vascular complications, extremity surgery with prolonged tourniquet application.


PubMed | Agr Ibrahim Cecen University, University of Florence, Ondokuz Mayis University, Fatih University and 4 more.
Type: Journal Article | Journal: Bioorganic & medicinal chemistry | Year: 2015

The inhibition of two human cytosolic carbonic anhydrase isozymes I and II, with some novel glycine and phenylalanine sulfonamide derivatives were investigated. Newly synthesized compounds G1-4 and P1-4 showed effective inhibition profiles with KI values in the range of 14.66-315M for hCA I and of 18.31-143.8M against hCA II, respectively. In order to investigate the binding mechanisms of these inhibitors, in silico docking studies were applied. Atomistic molecular dynamic simulations were performed for docking poses which utilize to illustrate the inhibition mechanism of used inhibitors into active site of CAII. These sulfonamide containing compounds generally were competitive inhibitors with 4-nitrophenylacetate as substrate. Some investigated compounds here showed effective hCA II inhibitory effects, in the same range as the clinically used sulfonamide, sulfanilamide or mafenide and might be used as leads for generating enzyme inhibitors possibly targeting other CA isoforms which have not been yet assayed for their interactions with such agents.


PubMed | Agr Ibrahim Cecen University, University of Art, University of Florence and Giresun University
Type: Journal Article | Journal: Bioorganic & medicinal chemistry letters | Year: 2016

Carbonic anhydrases (CAs, EC 4.2.1.1) are crucial metalloenzymes involved in many bioprocesses, through catalysis of the reversible hydration/dehydration process of CO


PubMed | Agr Ibrahim Cecen University, King Abdulaziz City for Science and Technology and Atatürk University
Type: Journal Article | Journal: Journal of animal physiology and animal nutrition | Year: 2016

This study was conducted to determine the effects of dietary cerium oxide levels (0, 100, 200, 300 or 400mg/kg) on the laying performance, egg quality, some blood serum parameters and egg lipid peroxidation of laying hen. In total, one hundred and twenty 22-week-old brown Lohman LSL laying hens were randomly assigned to five groups equally (n=24). Each treatment was replicated six times. Dietary supplementation of cerium oxide had no significant effect on feed intake and egg weight. The addition of cerium oxide to the laying hens feed improved feed conversion ratio and increased (p<0.05) egg production. Quality criteria of egg for except shell breaking strength were not affected by supplementing cerium oxide. In particular, supplementation of 200 and 300mg/kg cerium oxide to the laying hens feed led to a significant (p<0. 01) increase in egg shell breaking strength. Calcium and phosphorus concentration of serum increased significantly (p<0.05) with supplementation of 100mg/kg cerium oxide to laying hen diets. It was also observed that serum superoxide dismutase (SOD) activity and malondialdehyde (MDA) concentration decreased significantly with supplementation of cerium oxide in diets. Inclusion of cerium oxide resulted in a significant reduction in thiobarbituric acid reactive substance (TBARS) values in egg yolk in this study. It can be concluded that the addition of cerium oxide had positive effects on egg production, feed conversion ratio and egg shelf life. Based on the results of this study, it could be advised to supplement laying hens feed with cerium oxide as feed additives.


PubMed | Agr Ibrahim Cecen University, Technical University of Istanbul and Bahcesehir University
Type: Journal Article | Journal: Journal of enzyme inhibition and medicinal chemistry | Year: 2016

Carbonic anhydrase type IX (CA IX) enzyme is mostly over expressed in different cancer cell lines and tumor tissues. Potent CA IX inhibitors can be effective for adjusting the pH imbalance in tumor cells. In the present work, we represented the successful application of high throughput virtual screening (HTVS) of large dataset from ZINC database included of 7 million compounds to discover novel inhibitors of CA IX. HTVS and molecular docking were performed using consequence Glide/standard precision (SP), extra precision (XP) and induced fit docking (IFD) molecular docking protocols. For each compound, docking code calculates a set of low-energy poses and then exhaustively scans the binding pocket of the target with small compounds. Novel CA IX inhibitor candidates were suggested based on molecular modeling studies and a few of them were tested using in vitro analysis. These compounds were determined as good inhibitors against human CA IX target with Ki in the range of 0.85-1.58M. In order to predict the pharmaceutical properties of the selected compounds, ADME (absorption, distribution, metabolism and excretion) analysis was also carried out.


Erturk F.A.,Eurasian University | Agar G.,Atatürk University | Arslan E.,Atatürk University | Nardemir G.,Agr Ibrahim Cecen University
Environmental Science and Pollution Research | Year: 2015

Conditions of environmental stress are known to lead genetic and epigenetic variability in plants. DNA methylation is one of the important epigenetic mechanisms and plays a critical role in epigenetic control of gene expression. Thus, the aim of the study was to investigate the alteration of genome methylation induced by zinc stress by using coupled restriction enzyme digestion-random amplification (CRED-RA) technique in maize (Zea mays L.) seedlings. In addition, to determine the effect of zinc on mitotic activity and phytohormone level, high-pressure liquid chromatography (HPLC) and mitotic index analysis were utilized. According to the results, mitotic index decreased in all concentrations of zinc except for 5 mM dose and chromosome aberrations such as c-mitosis, stickiness, and anaphase bridges were determined. It was also observed that increasing concentrations of zinc caused an increase in methylation patterns and decrease in gibberellic acid (GA), zeatin (ZA), and indole acetic acid (IAA) levels in contrast to abscisic acid (ABA) level. Especially increasing of ABA levels under zinc stress may be a part of the defense system against heavy metal accumulation in plants. © 2015, Springer-Verlag Berlin Heidelberg.


PubMed | Agr Ibrahim Cecen University, Ondokuz Mayis University and Dumlupinar University
Type: Journal Article | Journal: Bioorganic & medicinal chemistry letters | Year: 2015

Carbonic anhydrase (CA) inhibitors are valuable molecules based on several therapeutic applications, including antiglaucoma activity. In the present study, inhibition of two human cytosolic carbonic anhydrase isozymes I and II with some uracil derivatives (3-9) were investigated. Compounds 3-9 showed KI values in the range of 10.83-464 M for hCA I and of 28.88-778.5 M against hCA II, respectively. Kinetic investigations showed that similarly to classical CA inhibitors, all investigated natural compounds act as competitive inhibitors with 4-NPA as substrate. Uracil derivatives investigated here are promising agents which may be used as lead molecules in order to derivative novel carbonic anhydrase inhibitors that might be useful in medical applications.


Bahcivan E.,Abant Izzet Baysal University | Kapucu S.,Agr Ibrahim Cecen University
International Journal of Environmental and Science Education | Year: 2014

This study has been conducted to investigate conceptions of learning science (COLS) and personal science teaching efficacy belief (PSTE) of Turkish preservice elementary science teachers (PSTs) and to explore the relationship between these variables. Two instruments COLS questionnaire and PSTE subscale of Science Teaching Efficacy Beliefs Instrument (STEBI-B) have been administered to 379 PSTs from seven different universities. Descriptive analyses have pointed out that PSTs have higher level of COLS and moderately higher level of PSTE. The results obtained from the structural equation model have revealed that the conceptions ‘testing’, ‘calculate and practice’, ‘increase of knowledge’, ‘applying’ and ‘understanding and seeing in a new way’ have significantly predicted PSTE. We have assumed that lower level of conceptions ‘memorizing’, ‘testing’, and ‘calculate and practice’ predict PSTE by negative coefficients while higher level of conceptions ‘increase of knowledge’, ‘applying’ and ‘understanding and seeing in a new way’ predict by positive coefficients. However, ‘calculating and practicing’ has positively predicted and ‘applying’ has negatively predicted PSTE. Considering the results, adaptation of inquiry- and argumentation-based learning and teaching environments in science teacher education, creating opportunities to develop PSTs’ pedagogical skills about knowledge transfer and application, and utilization of diagnostic tools to pursue PSTs’ development of COLS have been suggested. © 2014 by iSER, International Society of Educational Research.

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