Publications by authors named "Yavuz Erden"

14 Publications

  • Page 1 of 1

Design, synthesis, characterization, enzymatic inhibition evaluations, and docking study of novel quinazolinone derivatives.

Int J Biol Macromol 2021 Feb 19;170:1-12. Epub 2020 Dec 19.

Department of Chemistry, Faculty of Sciences, Ataturk University, 25240, Erzurum, Turkey.

In this study, novel quinazolinone derivatives 7a-n were synthesized and evaluated against metabolic enzymes including α-glycosidase, acetylcholinesterase, butyrylcholinesterase, human carbonic anhydrase I, and II. These compounds exhibited high inhibitory activities in comparison to used standard inhibitors with K values in the range of 19.28-135.88 nM for α-glycosidase (K value for standard inhibitor = 187.71 nM), 0.68-23.01 nM for acetylcholinesterase (K value for standard inhibitor = 53.31 nM), 1.01-29.56 nM for butyrylcholinesterase (K value for standard inhibitor = 58.16 nM), 10.25-126.05 nM for human carbonic anhydrase I (K value for standard inhibitor = 248.18 nM), and 13.46-178.35 nM for human carbonic anhydrase II (K value for standard inhibitor = 323.72). Furthermore, the most potent compounds against each enzyme were selected in order to evaluate interaction modes of these compounds in the active site of the target enzyme. Cytotoxicity assay of the title compounds 7a-n against cancer cell lines MCF-7 and LNCaP demonstrated that these compounds do not show significant cytotoxic effects.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.12.121DOI Listing
February 2021

Metal contained Phthalocyanines with 3,4-Dimethoxyphenethoxy substituents: their anticancer, antibacterial activities and their inhibitory effects on some metabolic enzymes with molecular docking studies.

J Biomol Struct Dyn 2020 Nov 24:1-12. Epub 2020 Nov 24.

Department of Chemistry, Faculty of Science, Ataturk University, Erzurum, Turkey.

The compounds (-) used in this study were re-synthesized in accordance with our previous study. The inhibitory effect of the complexes on some metabolic enzymes was examined and it was demonstrated that the enzymes inhibited by ligands and their complex molecules at micromolar level. The best Ki value for α-glycosidase enzyme was absorved 1.01±0.08 µM for compound . The biological activity of ligand and metal complexes against enzymes was compared with molecular docking method. The enzymes used against ligand and metal complexes respectively: Achethylcholinesterase for ID 4M0E (AChE), butyrylcholinesterase for ID 5NN0 (BChE), α-glycosidase for ID 1XSI (α-Gly). ADME analysis was performed to examine the drug properties of the compounds (-). Besides, the anticancer properties of the complexes were studied. The doses of all compounds caused significant reductions in MCF-7 cell viability. The and compounds administered to PC-3 cells exhibited a more pronounced cytotoxic effect than the other two compounds ( and ). Furthermore, antibacterial activities of these compounds against and were examined. Communicated by Ramaswamy H. Sarma.
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http://dx.doi.org/10.1080/07391102.2020.1844051DOI Listing
November 2020

Capsanthin Stimulates the Mitochondrial Apoptosis-Mediated Cell Death, following DNA Damage in MCF-7 Cells.

Authors:
Yavuz Erden

Nutr Cancer 2021 16;73(4):662-670. Epub 2020 Sep 16.

Department of Molecular Biology and Genetics, Faculty of Science, Bartin University, Bartin, Turkey.

Carotenoids found in fruits and vegetables are compounds with significant biological activities. Epidemiological studies report that these compounds have significant anticancer effects, as well reducing the risk of cancer. In the present study, we aimed to determine the effects of capsanthin, an important carotenoid of paprika, on expressions of proteins playing roles in the mitochondrial apoptosis pathway, in addition to its possible cytotoxic and genotoxic effects in MCF-7 cells. Furthermore, possible oxidant/anti-oxidant roles of capsanthin on MCF-7 cells were investigated. The viability of MCF-7 cells was significantly decreased after 24 h of capsanthin application. After Comet analysis, it was determined that the capsanthin caused DNA damage on a dose-dependent manner. Furthermore, Western blot analysis showed that capsanthin application increased p53 and Bax protein expressions and caused a decrease in Bcl-2 protein level. Capsanthin treatment decreased catalase and glutathione levels but increased lipid peroxidation. These results show that the capsanthin causes oxidative stress and DNA damage, and increases mitochondrial apoptotic mechanism-mediated cell death after p53 and Bax protein activations.
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http://dx.doi.org/10.1080/01635581.2020.1819347DOI Listing
September 2020

Cytotoxic effects, carbonic anhydrase isoenzymes, α-glycosidase and acetylcholinesterase inhibitory properties, and molecular docking studies of heteroatom-containing sulfonyl hydrazone derivatives.

J Biomol Struct Dyn 2020 Jul 21:1-12. Epub 2020 Jul 21.

Department of Chemistry, Faculty of Sciences, Ataturk University, Erzurum, Turkey.

Today, interest in studies on the search for new drugs to be used in diseases such as cancer, cardiovascular diseases, neurodegenerative diseases and diabetes, as well as prevention of microbial inflammation is increasing day by day. Emerging biological and pharmacological effects of sulfonyl hydrazone derivative compounds reveal their importance. In the present study, heteroatom-containing sulfonyl hydrazone derivatives have been studied for their anticancer and antimicrobial properties, as well as their effects on enzymes that could play roles in Alzheimer's dissease and diabetes. High doses of the tested compounds significantly decreased the cell viabilities of breast cancer (MCF-7) and prostate cancer (PC-3) cell lines. Furthermore, all compounds possessed antimicrobial activities against very common bacteria and . These compounds were good inhibitors of the α-glycosidase, human carbonic anhydrase I and II isoforms and acetylcholinesterase enzyme with values in the range of 1.14 ± 0.14-3.63 ± 0.26 nM for α-glycosidase, 66.05 ± 9.21-125.45 ± 11.54 nM for hCA I, 89.14 ± 10.43-170.22 ± 26.05 nM for hCA II and 754.03 ± 73.22-943.92 ± 58.15 nM for AChE, respectively. Molecular docking method was used to theoretically compare biological activities of sulfonyl hydrazone derivatives against enzymes. The theoretical results were compared with the experimental results. Thus, these compounds have strong biological activities. Communicated by Ramaswamy H. Sarma.
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http://dx.doi.org/10.1080/07391102.2020.1792345DOI Listing
July 2020

Determination of anticancer properties and inhibitory effects of some metabolic enzymes including acetylcholinesterase, butyrylcholinesterase, alpha-glycosidase of some compounds with molecular docking study.

J Biomol Struct Dyn 2020 Jun 4:1-10. Epub 2020 Jun 4.

Department of Chemistry, Faculty of Science, Ataturk University, Erzurum, Turkey.

Inhibitory effect of the complexes on some metabolic enzyme demonstrated that the enzymes inhibited by ligand and it's complex molecules at the micromolar level. The best inhibition effect for α-glycosidase (α-Gly) enzyme against cobalt complex with Ki value of 3.77 ± 0.58 µM. For achethylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes against SM-Co complex, Ki values of 74.23 ± 5.02 µM and 101.21 ± 12.84 µM Ki were observed, respectively. Molecular docking studies were performed to compare the biological activities of ligands and ligand complexes against enzymes whose names are AChE for ID 4M0E, BChE for ID 5NN0, α-Gly for ID 1XSI respectively. Also, anticancer properties of the complexes studied. The doses of all compounds caused significant reductions in MCF-7 cell viability. Zr compound showed the best cytotoxic activity against the MCF-7 cell. SM ligand administered to PC-3 cells exhibited a more pronounced cytotoxic effect than the SM-Co and Zr compounds.Communicated by Ramaswamy H. Sarma.
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http://dx.doi.org/10.1080/07391102.2020.1768901DOI Listing
June 2020

The biological activities, molecular docking studies, and anticancer effects of 1-arylsuphonylpyrazole derivatives.

J Biomol Struct Dyn 2020 May 15:1-11. Epub 2020 May 15.

Faculty of Sciences, Department of Chemistry, Ataturk University, Erzurum, Turkey.

This work is devoted to definition of the direction of reaction between 1-benzenesulfonylimino pyridinium chloride and α- or β-halo-containing sulfamides, chloroacetic acid, 1-chloro-2,3-dihydroxypropane, etc. The optimal conditions for the synchronous reaction of heterocyclization are determined. Benzenesulfonyliminopyridinium chloride was obtained to form pyrazolopyridines with 1,2-polarophiles, and pyridazine pyridines with 1,3-polarophiles. These novel derivatives were found as effective inhibitors of the α-glycosidase with K values in the range of 13.66 ± 2.63-60.63 ± 12.71 nM. The molecules () against enzyme were compared theoretically with the help of molecular docking to compare biological activities. The results were compared with the numerical values of the parameters obtained from molecular docking calculations and found to be in great agreement with the experimental results. However, ADME analysis of molecules was performed. Also, the compounds exhibited significant anticancer effect depending on the doses administered.Communicated by Ramaswamy H. Sarma.
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http://dx.doi.org/10.1080/07391102.2020.1763838DOI Listing
May 2020

Protective effect of saxagliptin against renal ischaemia reperfusion injury in rats.

Arch Physiol Biochem 2020 Jan 24:1-11. Epub 2020 Jan 24.

Faculty of Medicine, Department of Physiology, Inonu University, Malatya, Turkey.

Saxagliptin is an effective and selective dipeptidyl peptidase-4 (DPP-4) inhibitor. This study was designed to determine possible protective effects of saxagliptin against damage caused by renal ischaemia/reperfusion (I/R) in rats. In this study, 40 rats were divided into 4 groups ( = 10 for each). Group 1 (Control), Group 2 (I/R) in both kidneys ischaemia of 45 min was performed, and then reperfusion was applied for 24 h. Saxagliptin (Group 3: 2 mg/kg and Group 4: 10 mg/kg) was administered by oral gavage to the animals in treatment groups, before the I/R. Saxagliptin decreased the markers (BUN, Cre, NGAL, KIM-1 and IL-18) of acute renal damage in blood and kidney tissue. Saxagliptin provided increase in antioxidant enzyme levels and decrease in MDA and apoptosis. Histological results showed that the administration of saxagliptin exhibited a protective effect against renal damage caused by I/R. These results indicates that saxagliptin provide protection against kidney injury caused by I/R.
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http://dx.doi.org/10.1080/13813455.2020.1715442DOI Listing
January 2020

Novel tribenzylaminobenzolsulphonylimine based on their pyrazine and pyridazines: Synthesis, characterization, antidiabetic, anticancer, anticholinergic, and molecular docking studies.

Bioorg Chem 2019 12 24;93:103313. Epub 2019 Sep 24.

Department of Chemistry, Faculty of Sciences, Ataturk University, 25240 Erzurum, Turkey.

A new method of obtaining multifunctional pyrazoles by the reaction of 1,3-dipolar addition of tribenzylsulfonyliminochloride to polarophiles has been developed. This imine is obtained by reacting tribenzylamine with N-chlorobenzene sulfamide (chloramine-B). Regardless of the structure and composition of polarophiles, the cyclization reaction takes place in the presence of alkali in 6-8 h of boiling, which proves the activation of the methylene groups of tribenzylamine using the electron-withdrawing sulfonamide group. These novel derivatives were effective inhibitors of the α-glycosidase, butyrylcholinesterase (BChE), and acetylcholinesterase enzymes (AChE) with Ki values in the range of 0.45 ± 0.08-1.24 ± 0.27 µM for α-glycosidase, 6.04 ± 0.95-11.61 ± 2.84 µM for BChE, and 2.04 ± 0.24-4.23 ± 1.02 µM for AChE, respectively. The biological activities of the studied molecules against enzyme molecules were investigated by molecular docking calculations. The enzymes studied were AChE for ID 4M0E, BChE for ID 5NN0 BChE, and α-Glycosidase for ID 1XSI (α-Gly) respectively.
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http://dx.doi.org/10.1016/j.bioorg.2019.103313DOI Listing
December 2019

Cannabinoid type 2 receptor agonist JWH-133, attenuates Okadaic acid induced spatial memory impairment and neurodegeneration in rats.

Life Sci 2019 Jan 28;217:25-33. Epub 2018 Nov 28.

Faculty of Medicine, Department of Physiology, University of Inonu, Malatya 44280, Turkey.

Aim: Cannabinoid system has various physiological roles such as neurogenesis, synaptic plasticity and emotional state regulation in the body. The presence of cannabinoid type 2 receptor (CB2), a member of the cannabinoid system, was detected in different regions of the brain. CB2 receptor plays a role in neuroinflammatory and neurodegenerative processes. We aimed to determine the possible effect of CB2 agonist JWH-133 in Okadaic acid (OKA)-induced neurodegeneration model mimicking Alzheimer's Disease (AD) through tau pathology.

Materials And Methods: In this study, 40 Sprague Dawley male rats were divided into 4 groups (Control, Sham, OKA, OKA + JWH-133). Bilateral intracerebroventricular (icv) injection of 200 ng OKA was performed in the OKA group. In the OKA + JWH-133 group, injection of JWH-133 (0.2 mg/kg) was performed intraperitoneally for 13 days different from the group of OKA. Morris water maze test was used to evaluate the spatial memory. Levels of caspase-3, phosphorylated tau (ser396), amyloid beta (Aβ), tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) levels in brain cortex; and the hippocampus regions were examined by immunohistochemical methods.

Key Findings: In the OKA group, caspase-3, phosphorylated tau (ser396), Aβ, IL-1β levels were higher in the cortex and hippocampus than in the other groups. The implementation of the JWH-133 reversed the increments in these parameters, and also prevented spatial memory impairment.

Significance: In this study, we found that the administration of the CB2 receptor agonist JWH-133 in this study reduced neurodegeneration, neuroinflammation, and spatial memory impairment in the OKA-induced Alzheimer's Disease model.
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http://dx.doi.org/10.1016/j.lfs.2018.11.058DOI Listing
January 2019

Effects of intracerebroventricular administration of irisin on the hypothalamus-pituitary-gonadal axis in male rats.

J Cell Physiol 2019 06 14;234(6):8815-8824. Epub 2018 Oct 14.

Department of Physiology, Faculty of Medicine, Inonu University, Malatya, Turkey.

Irisin is a product of fibronectin type III domain-containing protein 5 (FNDC5) and plays an important role in energy homeostasis. In this study, we aimed to determine effects of intracerebroventricular administration of irisin on the hypothalamus-pituitary-gonadal axis by molecular, biochemical, and morphological findings. Fourty male Wistar-Albino rats were used and divided into four groups including control, sham (vehicle), 10, and 100 nM irisin infused groups (n = 10). Hypothalamic gonadotropin releasing hormone (GnRH) level and serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone levels were determined. Testicular tissue histology and spermiogram analysis were also performed. Both irisin concentrations significantly reduced hypothalamic GnRH messenger RNA (mRNA) and protein levels (p < 0.05). It was found that serum LH, FSH, and testosterone levels and Sertoli and Leydig cell numbers were decreased by irisin administration (p < 0.05). In addition, irisin administration reduced sperm density and mobility (p < 0.05). However, it did not cause any change in testicular and epididymis weights and tubular diameter. Our results reveal that irisin can play a role in the central regulation of reproductive behavior and also reduces testosterone levels by suppressing LH and FSH secretion. These results suggest that the discovery of irisin receptor antagonists may be beneficial in the treatment of infertility.
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http://dx.doi.org/10.1002/jcp.27541DOI Listing
June 2019

Central irisin administration suppresses thyroid hormone production but increases energy consumption in rats.

Neurosci Lett 2018 05 21;674:136-141. Epub 2018 Mar 21.

Inonu University, Faculty of Medicine, Department of Physiology, Malatya, Turkey. Electronic address:

Irisin, which is secreted from the skeletal muscle in response to physical exercise and defined as a thermogenic peptide, may play an important role in energy metabolism. Thyroid hormones, which are one of the other influential factors on the metabolic status, increase heat production and are the main regulators of energy metabolism. This study was conducted to determine the possible effects of irisin administration on thyroid hormones. Forty adult male Wistar albino rats were used in the study. The rats were equally divided into 4 groups (n = 10). The brain infusion kit was implanted in the groups, and irisin (or solvent as control) was centrally administered to the rats via osmotic mini pumps for 7 days. During the experiment, food consumption, body weights, and body temperatures of the animals were recorded. Food intake was significantly increased in the groups treated with irisin (p < 0.05), but their body weights were not changed. Hypothalamic TRH gene expression, serum TSH, fT3, and fT4 levels were significantly lower in the groups treated with irisin as compared to the naive and control groups (p < 0.05). In addition, irisin increased UCP1 mRNA expression in white and brown adipose tissue and UCP3 mRNA expression in muscle tissue in rats and also raised their body temperature (p < 0.05). Consequently, although central irisin administration has inhibitory effects on the hypothalamic-pituitary-thyroid axis, it seems to be an important agent in the regulation of food intake and energy metabolism.
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http://dx.doi.org/10.1016/j.neulet.2018.03.046DOI Listing
May 2018

The effects of intracerebroventricular infusion of irisin on feeding behaviour in rats.

Neurosci Lett 2017 04 24;645:25-32. Epub 2017 Feb 24.

Inonu University, Faculty of Medicine, Department of Physiology, Malatya, Turkey. Electronic address:

Irisin, a novel exercise-induced myokine, has attracted attention with its effects on energy metabolism. This study was conducted to determine the possible effects of irisin on nutritional behaviour. In this study, 40 male Wistar Albino rats were separated into 4 groups (n=10 for each group). Osmotic mini-pumps were connected to metal cannulas implanted to lateral ventricle; and artificial cerebrospinal fluid (vehicle), and 10 and 100nM of irisin was infused for 7days. The daily food and water consumptions and body weights of rats were followed up. After the infusion, the animals were killed, and the hypothalamus and blood samples were collected. NPY, POMC, and UCP2 mRNA levels in the hypothalamus were examined by RT-PCR. In serum, leptin and ghrelin levels as well as the levels of metabolic parameters were measured by using ELISA. It was determined that irisin administration increased the daily food consumption (p<0.05), without causing significant changes in water consumption and body weight. Irisin also caused increases in ghrelin level in circulation and NPY and UCP2 mRNA levels in the hypothalamus, whereas it decreased the leptin level in circulation and POMC mRNA levels in the hypothalamus (p<0.05). Otherwise, irisin caused decrease in LDL, triglycerides and cholesterol levels, while increasing HDL and glucose levels (p<0.05). Results indicates that long-term irisin treatment increases food intake without increasing body weight associated with increased ghrelin, NPY and UCP2 mRNAs, and decreased leptin and POMC mRNA in the hypothalamus.
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http://dx.doi.org/10.1016/j.neulet.2017.02.066DOI Listing
April 2017

Effects of apelin on reproductive functions: relationship with feeding behavior and energy metabolism.

Arch Physiol Biochem 2017 Feb 5;123(1):9-15. Epub 2016 Aug 5.

f Department of Physiology , Faculty of Medicine, Yeditepe University , Istanbul , Turkey.

Apelin is an adipose tissue derived peptidergic hormone. In this study, 40 male Sprague-Dawley rats were used (four groups; n = 10). Apelin-13 at three different dosages (1, 5 and 50 μg/kg) was given intraperitoneally while the control group received vehicle the same route for a period of 14 days. In results, apelin-13 caused significant decreases in serum testosterone, luteinizing hormone and follicle-stimulating hormone levels (p < 0.05). Administration of apelin-13 significantly increased body weights, food intake, serum low-density lipoprotein and total cholesterol levels (p < 0.05), but caused significant decreases in high-density lipoprotein levels (p < 0.05). Serum glucose and triglyceride levels were not significantly altered by apelin-13 administration. Significant decreases in both uncoupling protein (UCP)-1 levels in the white and brown adipose tissues and UCP-3 levels in the biceps muscle (p < 0.05) were noted. The findings of the study suggest that apelin-13 may not only lead to obesity by increasing body weight but also cause infertility by suppressing reproductive hormones.
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http://dx.doi.org/10.1080/13813455.2016.1211709DOI Listing
February 2017

Effects of central irisin administration on the uncoupling proteins in rat brain.

Neurosci Lett 2016 Apr 27;618:6-13. Epub 2016 Feb 27.

Department of Biology, Faculty of Science, Firat University, Elazig, Turkey.

Irisin is a thermogenic peptide that enables the development of brown adipose tissue from white adipose tissue by activating the UCP1. This study has been designed to determine the effects of the irisin on UCPs. Sprague Dawley female rats were used in the study. 1, 3 and 10μM concentrations of irisin were injected intracerebroventricularly to the rats, and the control group was received only vehicle. The animals were killed at the 16, 24, and 48h time intervals and their brains were taken out. The hypothalamus, pituitary gland, hippocampus, cerebellum, striatum and cortex areas were separated and the UCP2, UCP3, UCP4 and UCP5 mRNA levels were determined. Just before the animals were killed, their body temperatures were recorded. It was observed that after application of the high dose irisin, UCP5 mRNA level in the all brain areas increased (p<0.05); it was also observed that the three doses decreased the UCP4 expression in all brain areas (except the pituitary gland; p<0.05). The UCP2 and UCP3 mRNA expressions showed significantly increase in cerebellum and striatum (p<0.05). The UCP2 mRNA expression decreased in hypothalamus, pituitary gland, hippocampus and cortex areas (p<0.05). It was also observed that the body temperatures of the rats increased depending on the irisin injection and this increase was the most considerable at the 24h (p<0.05). The results of this study suggest that the UCP2-5 is expressed in different areas of the brain, and the irisin affects this expression, and may have effective roles in some brain functions.
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http://dx.doi.org/10.1016/j.neulet.2016.02.046DOI Listing
April 2016