Browsing by Author "Turkan, Fikret"

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Co and Zn Metal Phthalocyanines With Bulky Substituents: Anticancer, Antibacterial Activities and Their Inhibitory Effects on Some Metabolic Enzymes With Molecular Docking Studies
(Taylor & Francis Ltd, 2022) Turkan, Fikret; Taslimi, Parham; Cabir, Beyza; Agirtas, Mehmet Salih; Erden, Yavuz; Celebioglu, Hasan Ufuk; Gulcin, Ilhami
In this study, we reported the synthesis of new cobalt and zinc phthalocyanine compounds with ((ethylenediamine-N,N',N'-triacetic acid-N-2-ethyl)oxy) (ETAEO) substituted groups. Characterization studies and anticancer properties of both synthesized compounds were determined as well. The inhibitory effects of these complexes on some metabolic enzymes were examined and it was observed that the enzymes inhibited by complex molecules at the micromolar levels. In addition, the active sites of the enzymes were determined by molecular modeling programme for screening the enzyme-inhibitor interactions. The molecular docking method was used to calculate the interactions of molecules with enzymes. Also, human prostate and breast cancer cell lines (PC-3 and MCF-7) were used to determine the anticancer properties of the complexes. All doses of the tetrakis (ETAEO) phthalocyaninato Cobalt II (1) did not show any significant changes in PC-3 cell viability, but significantly reduced in MCF-7 cell viability. Similarly, all doses of the tetrakis (ETAEO) phthalocyaninato zinc II (2) significantly reduced MCF-7 cell viability compared to the control and solvent control groups. According to the enzyme inhibition studies, both complexes showed the best inhibition effects for alpha-Glycosidase enzyme with 125.85 +/- 30.35 mu M and 165.30 +/- 27.18 mu M Ki values.
Comparison of the Protective Effects of Curcumin and Caffeic Acid Phenethyl Ester Against Doxorubicin-Induced Testicular Toxicity
(Wiley, 2021) Huyut, Zubeyir; Alp, Hamit Hakan; Yaman, Turan; Keles, Omer Faruk; Yener, Zabit; Turkan, Fikret; Ayengin, Kemal
Whether testicular toxicity is mediated by matrix metalloproteinases (MMPs) is an important question that has not been examined. This study investigated the suppressive effect of curcumin and caffeic acid phenethyl ester (CAPE) on oxidative stress, apoptosis, and whether MMPs mediate doxorubicin (DOX)-induced testicular injury. Male rats were randomly divided into eight groups (n = 8 per group). The groups were as follows: sham, dimethyl sulphoxide (100 mu L), DOX (3 mg/kg), CAPE (2.68 mg/kg), curcumin (30 mg/kg), DOX+CAPE (3 mg/kg DOX and 2.68 mg/kg CAPE), DOX+curcumin (3 mg/kg DOX and 30 mg/kg curcumin) and DOX+CAPE+curcumin (3 mg/kg DOX, 2.68 mg/kg CAPE and 30 mg/kg curcumin). Injections were administered daily for 21 days. The oxidative stress, MMPs, proinflammatory cytokines and apoptotic markers in the DOX group were higher than the sham group (p < .05); these measures were lower in the groups treated with CAPE and curcumin together with DOX compared with the DOX group (p < .05). The results showed that MMPs mediated DOX-induced testicular injury, but CAPE and especially curcumin suppressed testis injury and cell apoptosis by suppressing DOX-induced increases in MMPs, oxidative stress and proinflammatory cytokines. However, curcumin exhibited more pronounced effects than CAPE in terms of all studied parameters.
Determination of Anticancer Properties and Inhibitory Effects of Some Metabolic Enzymes Including Acetylcholinesterase, Butyrylcholinesterase, Alpha-Glycosidase of Some Compounds With Molecular Docking Study
(Taylor & Francis inc, 2021) Turkan, Fikret; Taslimi, Parham; Abdalrazaq, Sakar Mubarak; Aras, Abdulmelik; Erden, Yavuz; Celebioglu, Hasan Ufuk; Gulcin, Ilhami
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 alpha-glycosidase (alpha-Gly) enzyme against cobalt complex with Ki value of 3.77 +/- 0.58 mu M. For achethylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes against SM-Co complex, Ki values of 74.23 +/- 5.02 mu M and 101.21 +/- 12.84 mu M 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, alpha-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
Effects of Artemisinin on Anti-Epileptogenic, Antioxidant and Cholinesterase Enzymes in Pentylenetetrazole-Induced Kindling Model in Mice
(Assoc Pharmaceutical Teachers india, 2023) Kocak, Yilmaz; Yunusoglu, Oruc; Huyut, Zubeyir; Turkan, Fikret
Background: Artemisinin (ART) is a compound synthesized from the plant Artemisia annua. This compound has various therapeutic effects and is widely used against malaria. However, ART is known to have modulating effects on GABA (gamma-aminobutyric acid) receptors, which are thought to be responsible for epileptic seizures. This study aimed to evaluate the effects of ART on anti-convulsant, antioxidant, and cholinesterase enzyme activities in Pentylenetetrazole (PTZ)-induced kindling model in mice. Materials and Methods: In the experiment, 6 groups were formed, with seven mice in each group. Mice received a total of 11 intraperitoneal injections of PTZ (35 mg/kg). On the last day of the study, a threat dose of PTZ (75 mg/kg) was administered. In addition, behavioral analysis tests (Locomotor activity and rotarod) and biochemical measurements were performed. Results: Compared with the PTZ group, ART attenuated the severity of the kindling, decreasing the seizure score. ART and VPA reversed increased oxidative stress. Decreased cholinesterase enzymes in PTZ-induced brain increased with ART treatment. While the PTZ application impaired locomotor activity in mice, the ART application provided improvement in locomotor activity. However, no significant difference was found between the groups in the motor performance of the mice. Conclusion:The findings show that ART may have the potential to prevent PTZ-induced oxidative stress, neurochemical changes, behavioral disorders, and seizures.
Effects of Fluoride on Oxidative Dna Damage, Nitric Oxide Level, Lipid Peroxidation and Cholinesterase Enzyme Activity in a Rotenone-Induced Experimental Parkinson's Model
(Taylor & Francis Ltd, 2023) Kocak, Yilmaz; Oto, Gokhan; Huyut, Zubeyir; Alp, Hamit Hakan; Turkan, Fikret; Onay, Ezgi
ObjectiveEnvironmental toxins are known to be one of the important factors in the development of Parkinson's disease (PD). This study was designed to investigate the possible contribution of fluoride (F) exposure to oxidative stress and neurodegeneration in rats with PD induced by rotenone (ROT).Materials and methodsA total of 72 Wistar albino male rats were used in the experiment and 9 groups were formed with 8 animals in each group. ROT (2 mg/kg) was administered subcutaneously (sc) for 28 days. Different doses of sodium fluoride (NaF) (25, 50 and 100 ug/mL) were given orally (po) for 4 weeks. Malondialdehyde (MDA), glutathione (GSH), nitric oxide (NO), oxidative DNA damage (8-OHdG) and cholinesterase (AChE/BChE) enzyme activities were evaluated in serum and brain tissue homogenates.ResultsRats treated with ROT and NaF had significant increases in serum and brain MDA, NO content, and decreases in GSH. In addition, the combination of ROT and NaF triggered oxidative DNA damage and resulted in increased AChE/BChE activity.ConclusionsFindings suggest that NaF and ROT may interact synergistically leading to oxidative damage and neuronal cell loss. As a result, we believe that exposure to pesticides in combination with NaF is one of the environmental factors that should not be ignored in the etiology of neurological diseases such as PD in populations in areas with endemic fluorosis.
The Effects of Some Antibiotics From Cephalosporin Groups on the Acetylcholinesterase and Butyrylcholinesterase Enzymes Activities in Different Tissues of Rats
(Taylor & Francis Ltd, 2019) Turkan, Fikret; Huyut, Zubeyir; Taslimi, Parham; Gulcin, Ilhami
In our study, it was aimed to investigate the effects of cefazolin, cefuroxime, and cefoperazon injected to rats on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzyme activities in the heart, brain, eye, liver, and kidney tissues of rats. Liver AChE activity at the 1st and 3rd hours of cefuroxime groups was higher than the control group at the same time (p <.05). The AChE activity of the heart tissue decreased in the cefazolin group compared to the control group at the same hour, whereas it increased in the cefuroxime group (p <.05). AChE activities of kidney tissue of cefazolin and cefuroxime groups were lower than those of the same control group on the 3rd and started to increase on the next hours (p <.05). BChE activity is measured in tissues increased within the first three hours and decreased significantly within the first hour in the cefoperazone group (p <.05).
The Effects of Some Cephalosporins on Acetylcholinesterase and Glutathione S-Transferase: an in Vivo and in Vitro Study
(Taylor & Francis Ltd, 2019) Turkan, Fikret; Huyut, Zubeyir; Demir, Yeliz; Ertas, Fatma; Beydemir, Sukru
Background: Glutathione S-transferase (GST) and acetylcholinesterase (AChE) are important enzymes in the metabolism. GSTs are primarily available in phase II metabolism. AChE is vital for neurodegenerative disorders. Subjects and methods: The in vitro and in vivo effects of cefoperazone sodium (CFP), cefuroxime (CXM), and cefazolin (CZO) were investigated on GST and AChE activity in the present study. GST was purified using Glutathione-Agarose affinity chromatography. Results: K-i constants of CFP, CXM, and CZO were 0.1392 +/- 0.02, 1.5179 +/- 0.33, and 1.006 +/- 0.11 mM for GST and 0.3010 +/- 0.07, 0.3561 +/- 0.09, and 0.3844 +/- 0.04 mM, for AChE, respectively. The most effective inhibitor was CFP for both enzymes in in vitro. CZO (50 mg/kg), CXM (25 mg/kg), and CFP (100 mg/kg) inhibit in vivo GST and AChE activities. CXM had the most effective in vivo inhibition on AChE and GST. Conclusions: CZO, CXM, and CFP are effective AChE and GST inhibitors in both in vitro and in vivo.
In Vivo Biochemical Evaluations of Some Β-Lactam Group Antibiotics on Glutathione Reductase and Glutathione S- Transferase Enzyme Activities
(Pergamon-elsevier Science Ltd, 2019) Turkan, Fikret; Huyut, Zubeyir; Huyut, Mehmet Tahir; Calimli, Mehmet Harbi
Objectives: The aim of this study was to investigate whether some of the cephalosporin group antibiotics have inhibition effects on GR and GST enzymes with important functions in the metabolic pathway. Methods: In this study, some selected cephalosporin group antibiotics on GST and GR enzyme was carried out using 96 rats. 16 groups (16 x 6) were created from these rats, divided to another 4 groups (4 x 24). The resulting groups were named as sham groups, cefazolin groups, cefuroxime groups and cefoperazone groups, respectively. The antibiotics used were injected to cefazolin, cefuroxime and cefoperazone groups. The inhibition effects of the antibiotics were measured in the different time intervals (1st, 3th, 5th, 7th). The statistical investigation of the results was performed using the SPSS software program. Results: Results revealed the complex effects of the tested substances on GR and GST activity at different time intervals and in different tissues (p < 0.05). This indicated that the tested substances could be exposed to different interactions in vivo. Conclusion: The tested antibiotics showed some significant inhibition effects on the GST and GR enzyme activity in some tissues of brain, eye and muscle. The interaction of enzyme - the drug is a key factor to highlight the toxicological mechanism. For this reason, the results obtained from in vivo experiments are crucial to explane the physiological properties of the enzymes.
In Vivo Biochemical Evaluations of Some Β-Lactam Group Antibiotics on Glutathione Reductase and Glutathione S-Transferase Enzyme Activities (Vol 231, 116572, 2019)
(Pergamon-elsevier Science Ltd, 2023) Turkan, Fikret; Huyut, Zubeyir; Huyut, Mehmet Tahir; Calimli, Mehmet Harbi
The in Vivo Effects of Cefazolin, Cefuroxime, and Cefoperazon on the Carbonic Anhydrase in Different Rat Tissues
(Wiley, 2018) Turkan, Fikret; Huyut, Zubeyir; Taslimi, Parham; Gulcin, Ilhami
In this paper, the in vivo effects of some antibiotics including cefazolin, cefuroxime, and cefoperazon, on the activity of the carbonic anhydrase enzyme (CA) in heart, brain, eye, liver, and kidney tissues of rats were evaluated. For this purpose, 16 different groups, which each containing six rats (n = 6), were formed (control group, cefazolin groups, cefuroxime groups, and cefoperazon groups). The rats were necropsied 60 min after the intraperitoneal injection of the chemicals into the rats. The CA activities were measured for each tissue using esterase activity methods. The activity values for each tissue obtained were statistically calculated. The CA activities in the liver tissue were assessed, and the activities of the cefoperazon groups were decreased compared to the sham groups from the third hour (p<0.05). In the cefuroxime and cefoperazon groups, the CA activities in the eye tissue were decreased during the first 3 h and then increased (p<0.05).
Influence of Some Β-Lactam Drugs on Selected Antioxidant Enzyme and Lipid Peroxidation Levels in Different Rat Tissues
(Taylor & Francis Ltd, 2020) Turkan, Fikret; Huyut, Zubeyir; Basbugan, Yildiray; Gulcin, Ilhami
Antioxidant enzymes play an important role in body defense and free radical removal. Cephalosporins are beta-lactam antibiotics. In this work, the effects of cefazolin, cefuroxime and cefoperazone which are cephalosporins on some selected antioxidant enzyme and levels of malondialdehyde (MDA) as lipid peroxidation product were investigated in kidney, liver, and brain tissues of albino female rats. Ninety-six albino rats were randomly divided into 16 groups of equal number (n = 6). 50 mg/kg cefazolin, 25 mg/kg cefuroxime, and 100 mg/kg cefoperazone were injected intraperitoneally to the groups (5th-8th and 9th-12th, and 13th-16th groups), respectively. The changes in glutathione reductase (GR), glutathione S-transferase (GST), superoxide dismutase (SOD), peroxidase (POD), and glutathione peroxidase (GSH-Px) levels were studied in each time point group and a time-dependent manner (at the 1st, 3rd, 5th and 7th hour). In addition, MDA levels were examined in all the tissues. The drugs evaluated in this study had different effects on the same enzyme in different tissues depending on time. MDA levels especially in cefazolin and cefoperazone experiments were lower in all the tissues; however, MDA levels were higher in brain and kidney tissues in the cefuroxime groups in a time-dependent manner (p < 0.05). These results revealed the complex effects of the tested drugs on different tissues at different time points. Therefore, the dose and use of these drugs should be adjusted correctly.
Inhibition Effects of Isoproterenol, Chlorpromazine, Carbamazepine, Tamoxifen Drugs on Glutathione S-Transferase, Cholinesterases Enzymes and Molecular Docking Studies
(Taylor & Francis inc, 2021) Turkan, Fikret; Calimli, Mehmet Harbi; Kanberoglu, Gulsah Saydan; Karaman, Muhammet
Nowadays, inhibition of acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and glutathione S-transferases (GSTs) have been a very crucial issue for pharmacological treatments of several disasters. Herein, we investigated inhibition effects of Tamoxifen (TAM), Isoprenaline (ISO), Chlorpromazines (CPZ) and Carbamazepine (CBZ) on GST, AChE, BChE and then molecular structures and active sides of the tested drugs by molecular docking process. The enzyme activity results showed that nearly the whole tested drugs inhibited GST, BChE, AChE efficiently. Chlorpromazine was found to be the best inhibitor for the GST enzyme and the Ki value of this drug was found to be 42.83 +/- 8.52 nM. Besides, Isoproterenol drug with the Ki value of 51.80 +/- 9.44 nM was found to be the most effective inhibitor on the AChE enzyme. Molecular docking studies showed that the receptor-binding sites of GST, AChE, and BChE were found to 1.069, 1.090, and 1.15 of Sitecore and 0.992, 1.113, and 1.217 of Dscore, respectively. The method was validated by doing validation studies and these validations revealed that re-docked ligands located a very closed position with co-crystallized ligand into the active site for all receptors. Calculation studies for determining the possible enzyme inhibition mechanism with the used drugs revealed that amino and aromatic ring in the structure of the drugs used are effective in inhibition reactions. Communicated by Ramaswamy H. Sarma
Investigation of Interleukins and Oxidative Stress Parameters in Cows Naturally Infected With Bovine Viral Diarrhea Virus
(Univ Agriculture, Fac veterinary Science, 2024) Oguz, Fatma Ertas; Babaoglu, Ali Riza; Turkan, Fikret; Oguz, Ercan; Demirel, Ahmet Fatih; Pacal, Nurettin
Bovine Viral Diarrhea Virus (BVDV) can evade the immune system by modulating cytokines production, therefore enabling the virus to establish persistent infections or exacerbate the severity of disease in infected cattle. The objective of this research was to investigate interleukins and oxidative stress parameters in cows naturally infected with BVDV. The study comprised of two groups: a naturally infected group of 15 cattle with clinical signs of BVDV infection or a history of abortion and confirmed positive for pestivirus by RT-PCR, and a control group of 15 cattle with no abortion anamnesis or clinical symptoms, confirmed negative by RT-PCR. Anti-inflammatory cytokines (IL-4, IL-20, IL-10) and pro-inflammatory ones (IL-1, IL-1(3, IL-6) values were measured in all samples using ELISA method. Additionally, the oxidative stress marker malonaldehyde (MDA) was measured in all samples using the HPLC method. MDA levels were significantly higher in the infected samples compared with the controls. While cytokine levels were elevated in the infected group, however, the differences were not statistically significant. This study found a positive relationship among anti-inflammatory and pro-inflammatory cytokines, as well as a negative relationship among IL-1(3 and IL-1. It was concluded that oxidative stress occurs in BVDV-infected cattle, and the interleukins measured appear to remain in equilibrium by inhibiting each other. Notably, IL-20 was measured for the first time in BVDVinfected cattle, making it an important finding. Altogether, it may be concluded on the basis of these results that cytokines are important in the evaluation of the disease process.
Investigation of the Effects of Cephalosporin Antibiotics on Glutathione S-Transferase Activity in Different Tissues of Rats in Vivo Conditions in Order To Drug Development Research
(Taylor & Francis Ltd, 2020) Turkan, Fikret; Huyut, Zubeyir; Taslimi, Parham; Huyut, Mehmet Tahir; Gulcin, Ilhami
Glutathione S-transferases are multifunctional enzymes for the cellular defense against xenobiotics and provide protection for organism. In this study, the inhibition effects of some antibiotics were investigated against GST obtained from albino-rats kidney, liver, and heart tissues. Ninety-six albino-rats were randomly divided into 16 groups (n:6). The first four groups were control groups that were administrated blank enjection and decapitated at 1-7 h. The other groups were administrated the antibiotics. In all tissues, GST activity was increased in antibiotics groups at 1st and 3rd hours compared to control groups, while it began to fall at 5th and 7th hours (p < .05). In kidney tissues, it was lower than the same control group the cefuroxime and cefoperazone groups at 7th hours (p < .05). In addition, almost all antibiotic groups of kidney tissues had higher GST activity at all hours than those of control groups, but it was higher only at 5th hours in heart tissues (p < .05).
Metal Contained Phthalocyanines With 3,4-Dimethoxyphenethoxy Substituents: Their Anticancer, Antibacterial Activities and Their Inhibitory Effects on Some Metabolic Enzymes With Molecular Docking Studies
(Taylor & Francis inc, 2022) Taslimi, Parham; Turkan, Fikret; Gungordu Solgun, Derya; Aras, Abdulmelik; Erden, Yavuz; Celebioglu, Hasan Ufuk; Gulcin, Ilhami
The compounds (3-6) 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 alpha-glycosidase enzyme was absorved 1.01 +/- 0.08 mu M for compound 6. 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), alpha-glycosidase for ID 1XSI (alpha-Gly). ADME analysis was performed to examine the drug properties of the compounds (3-6). Besides, the anticancer properties of the complexes were studied. The doses of all compounds caused significant reductions in MCF-7 cell viability. The 3 and 5 compounds administered to PC-3 cells exhibited a more pronounced cytotoxic effect than the other two compounds (4 and 6). Furthermore, antibacterial activities of these compounds against Escherichia coli and Staphylococcus aureus were examined. Communicated by Ramaswamy H. Sarma
Pharmacological Assessment of Disulfide-Triazine Hybrids: Synthesis, Enzyme Inhibition, and Molecular Docking Study
(Springer Birkhauser, 2024) Turkan, Fikret; Cetin, Adnan; Rozbicki, Przemyslaw; Oguz, Ercan; Wolinska, Ewa; Branowska, Danuta
Acetylcholinesterase (AChE) is indispensable for neurotransmission, while glutathione S-transferase (GST) plays a crucial role in cellular detoxification and protection. These enzymes are pivotal subjects in scientific investigations aimed at understanding neurological functions and maintaining cellular equilibrium. In pursuit of this objective, a set of disulfide-triazine hybrids (1, 2, and 3a-h) was effectively synthesized and methodically examined for their capacity to inhibit both AChE and GST (the Ki values for AChE range from 0.893 +/- 0.117 mu M to 7.961 +/- 0.421 mu M, while the IC50 values fall within the range of 1.919-6.243 mu M. For GST, the Ki values span from 2.093 +/- 0.276 mu M to 8.840 +/- 1.934 mu M, with IC50 values ranging from 2.152 to 4.747 mu M). After synthesizing the compounds and studying their biological effects, molecular docking analyses were conducted to understand how these compounds interact with target enzymes. This helped identify how the compounds bind and which amino acid residues are crucial for inhibition. The positive results highlight the potential of disulfide-triazine hybrids as strong inhibitors of AChE and GST, suggesting they could be further developed and optimized as therapeutic agents.
Pyrazole[3,4-D]pyridazine Derivatives: Molecular Docking and Explore of Acetylcholinesterase and Carbonic Anhydrase Enzymes Inhibitors as Anticholinergics Potentials
(Academic Press inc Elsevier Science, 2019) Taslimi, Parham; Turkan, Fikret; Cetin, Adnan; Burhan, Hakan; Karaman, Muhammet; Bildirici, Ishak; Sen, Fatih
Recently, the pyridazine nucleus has been widely studied in the field of particular and new medicinal factors as drugs acting on the cardiovascular system. Additionally, a number of thienopyridazines have been claimed to possess interacting biological macromolecules and pharmacological activities such as NAD(P)H oxidase inhibitor, anticancer, and identified as a novel allosteric modulator of the adenosine A1 receptor. The literature survey demonstrates that coumarin, 1,2-pyrazole benzothiazole, and 1,3- thiazole scaffolds are the most versatile class of molecules. In this study, a series of substituted pyrazole[3,4-d]pyridazine derivatives (2a-n) were prepared, and their structures were characterized by Mass analysis, NMR, and FT-IR. These obtained pyrazole [3,4-d]pyridazine compounds were very good inhibitors of the carbonic anhydrase (hCA I and II) isoenzymes and acetylcholinesterase (AChE) with K-i values in the range of 9.03 +/- 3.81-55.42 +/- 14.77 nM for hCA I, 18.04 +/- 4.55-66.24 +/- 19.21 nM for hCA II, and 394.77 +/- 68.13-952.93 +/- 182.72 nM for AChE, respectively. The possible inhibition mechanism of the best-posed pyrazole[3,4-d]pyridazine and pyrazole-3-carboxylic acid derivatives and their interaction with catalytic active pocket residues were determined based on the calculations.
Rosmarinic Acid Inhibits Some Metabolic Enzymes Including Glutathione S-Transferase, Lactoperoxidase, Acetylcholinesterase, Butyrylcholinesterase and Carbonic Anhydrase Isoenzymes
(Taylor & Francis Ltd, 2016) Gulcin, Ilhami; Scozzafava, Andrea; Supuran, Claudiu T.; Koksal, Zeynep; Turkan, Fikret; Cetinkaya, Songul; Alwasel, Saleh H.
Rosmarinic acid (RA) is a natural polyphenol contained in many aromatic plants with promising biological activities. Carbonic anhydrases (CAs, EC 4.2.1.1) are widespread and intensively studied metalloenzymes present in higher vertebrates. Acetylcholinesterase (AChE, E.C. 3.1.1.7) is intimately associated with the normal neurotransmission by catalysing the hydrolysis of acetylcholine to acetate and choline and acts in combination with butyrylcholinesterase (BChE) to remove acetylcholine from the synaptic cleft. Lactoperoxidase (LPO) is an enzyme involved in fighting pathogenic microorganisms, whereas glutathione S-transferases (GSTs) are dimeric proteins present both in prokaryotic and in eukaryotic organisms and involved in cellular detoxification mechanisms. In the present study, the inhibition effects of rosmarinic acid on tumour-associated carbonic anhydrase IX and XII isoenzymes, AChE, BChE, LPO and GST enzymes were evaluated. Rosmarinic acid inhibited these enzymes with K(i)s in the range between micromolar to picomolar. The best inhibitory effect of rosmarinic acid was observed against both AChE and BChE.
Synthesis and Examination of 1,2,4-Triazine Hybrids as Potential Inhibitory Drugs: Inhibition Effects on Ache and Gst Enzymes in Silico and in Vitro Conditions
(Wiley-v C H verlag Gmbh, 2024) Rozbicki, Przemyslaw; Oguz, Ercan; Wolinska, Ewa; Turkan, Fikret; Cetin, Adnan; Branowska, Danuta
The crucial functions of acetylcholinesterase (AChE) in neurotransmission and glutathione S-transferase (GST) in detoxification and cellular protection underscore their pivotal roles as key enzymes, essential for maintaining the integrity of neurological and cellular homeostasis. For this purpose, a series of 1,2,4-triazine-sulfonamide hybrids (3a-r) was successfully synthesized, and subsequently evaluated for their inhibitory effects on AChE and GST. The investigation was complemented by molecular docking studies and ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) predictions. The synthesized hybrids demonstrated significant promise in inhibiting both AChE and GST activities. Molecular docking analyses provided insights into the interactions between the compounds and the target enzymes, shedding light on potential binding modes and key amino acid residues involved. Furthermore, the study benefited from ADMET predictions, offering valuable information on the compounds' pharmacokinetic properties and potential toxicity. The promising results obtained from this comprehensive approach highlight the potential of these 1,2,4-triazine-sulfonamide hybrids as effective inhibitors of AChE and GST, paving the way for further development and optimization in the pursuit of novel therapeutic agents. A series of 1,2,4-triazine-sulfonamide hybrids (3a-r) was synthesized and evaluated for their inhibitory effects on acetylcholinesterase (AChE) and glutathione S-transferase (GST). The hybrids demonstrated promising inhibition of both AChE and GST activities. Molecular docking analyses provided insights into the interactions between the compounds and the target enzymes. image
Synthesis and Investigation of the Conversion Reactions of Pyrimidine-Thiones With Nucleophilic Reagent and Evaluation of Their Acetylcholinesterase, Carbonic Anhydrase Inhibition, and Antioxidant Activities
(Wiley, 2018) Taslimi, Parham; Sujayev, Afsun; Turkan, Fikret; Garibov, Emin; Huyut, Zubeyir; Farzaliyev, Vagif; Gulcin, Ilhami
The conversion reactions of pyrimidine-thiones with nucleophilic reagent were studied during this scientific research. For this purpose, new compounds were synthesized by the interaction between 1,2-epoxy propane, 1,2-epoxy butane, and 4-chlor-1-butanol and pyrimidine-thiones. These pyrimidine-thiones derivatives (A-K) showed good inhibitory action against acetylcholinesterase (AChE), and human carbonic anhydrase (hCA) isoforms I and II. AChE inhibition was in the range of 93.1 +/- 33.7-467.5 +/- 126.9nM. The hCA I and II were effectively inhibited by these compounds, with K-i values in the range of 4.3 +/- 1.1-9.1 +/- 2.7nM for hCA I and 4.2 +/- 1.1-14.1 +/- 4.4nM for hCA II. On the other hand, acetazolamide clinically used as CA inhibitor showed K-i value of 13.9 +/- 5.1nM against hCA I and 18.1 +/- 8.5nM against hCA II. The antioxidant activity of the pyrimidine-thiones derivatives (A-K) was investigated by using different in vitro antioxidant assays, including Cu(2+)and Fe(3+)reducing, 1,1-diphenyl-2-picrylhydrazyl (DPPH center dot) radical scavenging, and Fe(2+)chelating activities.