Browsing by Author "Gulcin, Ilhami"

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Aminoalkylated Phenolic Chalcones: Investigation of Biological Effects on Acetylcholinesterase and Carbonic Anhydrase I and Ii as Potential Lead Enzyme Inhibitors
(Bentham Science Publ Ltd, 2020) Yamali, Cem; Gul, Halise Inci; Cakir, Tahir; Demir, Yeliz; Gulcin, Ilhami
Background: Phenolic Mannich bases have been reported as acetylcholinesterase (AChE) inhibitors for the medication of Alzheimer's disease. Carbonic Anhydrases (CAs) are molecular targets for anticonvulsant, diuretic and antiglaucoma drugs in the clinic. Phenolic compounds have also been mentioned as CA inhibitors. The importance of Mannich bases in drug design inspired our research group to design novel phenolic Mannic bases as potent enzyme inhibitors. Objective: In this study, novel Mannich bases, 1-(3,5-bis-aminomethyl-4-hydroxyphenyl)-3-(4-substitutedphenyl)-2-propen-1-ones (1-9), were designed to discover new and potent AChE inhibitors for the treatment of Alzheimer's disease and also to report their carbonic anhydrase inhibitory potency against the most studied hCA I and hCA II isoenzymes with the hope to find out promising enzyme inhibitors. Methods: Mannich bases were synthesized by the Mannich reaction. The structures of the compounds were elucidated by H-1 NMR, C-13 NMR, and HRMS. Enzyme inhibitory potency of the compounds was evaluated spectrophotometrically towards AChE, hCA I and hCA II enzymes. Results and Discussion: The compounds showed inhibition potency in nanomolar concentrations against AChE with Ki values ranging from 20.44 +/- 3.17 nM to 43.25 +/- 6.28 nM. They also showed CAs inhibition potency with Ki values in the range of 11.76 +/- 1.29-31.09 +/- 2.7 nM (hCA I) and 6.08 +/- 1.18-23.12 +/- 4.26 nM (hCA II). Compounds 1 (hCA I), 5 (hCA II), and 4 (AChE) showed significant inhibitory potency against the enzymes targeted. Conclusion: Enzyme assays showed that Mannich derivatives might be considered as lead enzyme inhibitors to design more selective and potent compounds targeting enzyme-based diseases.
Analysis of Phenolic Compounds by Lc-Hrms and Determination of Antioxidant and Enzyme Inhibitory Properties of Verbascum Speciousum Schrad
(Acg Publications, 2023) Kiziltas, Hatice; Bingol, Zeynebe; Goren, Ahmet C.; Alwasel, Saleh H.; Gulcin, Ilhami
Studies have shown an inverse correlation between age-related illnesses like coronary heart disease and cancer and fruit and vegetable intake. Given the probable health benefits of natural antioxidants from plants, research on them has increased. Verbascum L is a large genus of Scrophulariaceae family and 323 species distributed worldwide. Since Verbascum L. species are plants that are grown in many regions of Turkiye and are used in folk medicine, it is important to evaluate the biological activity of these species. In this study antioxidant properties of Verbascum speciosum Schrad. were investigated. The antioxidant capacities of water and ethanol-based extracts obtained from air parts were evaluated with Fe3+ reducing, CUPRAC, FRAP, DPPH center dot, and ABTS(center dot+) scavenging antioxidant methods. Extracts were also examined to determine their AChE, alpha-glycosidase and alpha-amylase enzyme inhibitions. This investigation could be a basis for further phytochemical investigations of Verbascum speciosum Schrad.
Anticholinergic, Antidiabetic and Antioxidant Activities of Ferula Orientalis L. Determination of Its Polyphenol Contents by Lc-Hrms
(Acg Publications, 2021) Kiziltas, Hatice; Goren, Ahmet C.; Bingol, Zeynebe; Alwasel, Saleh H.; Gulcin, Ilhami
To evaluate the antioxidant activity of evaporated ethanolic extract of Ferula orientalis L. (EEFO) and lyophilized water extract of Ferula orientalis L. (WEFO) several in vitro antioxidant methods such as ABTS(center dot+) scavenging activity, DPPH. scavenging activity, Fe(3+)reduction method, cupric ions (Cu2+) reduction capacity, and metal ion (Fe2+)-binding activities using ferrozine reagent were separately performed. Also, BHT, alpha-tocopherol and ascorbic acid were used as the standard antioxidant molecules. Moreover, some phenolic compounds that are responsible for antioxidant abilities of EEFO and WEFO were determined by LC-HRMS. EEFO and WEFO demonstrated effective antioxidant abilities when compared with the standards. EEFO demonstrated IC50 values of 1.946 mu g/mL against acetylcholinesterase (AChE), 0.815 mu g/mL against alpha-glycosidase, and 0.675 mu g/mL against alpha-amylase.
Antidiabetic, Anticholinergic and Antioxidant Activities of Aerial Parts of Shaggy Bindweed (Convulvulus Betonicifolia Miller Subsp.) - Profiling of Phenolic Compounds by Lc-Hrms
(Elsevier Sci Ltd, 2021) Bingol, Zeynebe; Kiziltas, Hatice; Goren, Ahmet C.; Kose, Leyla Polat; Topal, Meryem; Durmaz, Lokman; Gulcin, Ilhami
In order to evaluate the antioxidant activity of evaporated ethanolic extract (EESB) and lyophilized water extract (WESB) of Shaggy bindweed (Convulvulus betonicifolia Mill. Subs), some putative antioxidant methods such as DPPH. scavenging activity, ABTS(center dot)(-) scavenging effect, ferric ions (Fe3+) reduction method, cupric ions (Cu2+) reducing capacity, and ferrous ions (Fe2+) binding activities were separately performed. Also, ascorbic acid, alpha-tocopherol and BHT were used as the standard compounds. Additionally, some phenolic compounds that responsible for antioxidant abilities of EESB and WESB were screened by liquid chromatography-high resolution mass spectrometry (LC-HRMS). At the same concentration, EESB and WESB demonstrated effective antioxidant abilities when compared to standards. In addition, EESB demonstrated IC50 values of 1.946 mu g/mL against acetylcholinesterase (AChE), 0.815 mu g/mL against alpha-glycosidase and 0.675 mu g/mL against alpha-amylase enzymes.
Antioxidant and Antiradical Properties of Selected Flavonoids and Phenolic Compounds
(Hindawi Ltd, 2017) Huyut, Zubeyir; Beydemir, Sukru; Gulcin, Ilhami
Phenolic compounds and flavonoids are known by their antioxidant properties and one of the most important sources for humans is the diet. Due to the harmful effects of synthetic antioxidants such as BHA and BHT, natural novel antioxidants have become the focus of attention for protecting foods and beverages and reducing oxidative stress in vivo. In the current study, we investigated the total antioxidant, metal chelating, Fe3+ and Cu2+ reduction, and free radical scavenging activities of some phenolic and flavonoid compounds including malvin, oenin, ID-8, silychristin, callistephin, pelargonin, 3,4-dihydroxy-5-methoxybenzoic acid, 2,4,6-trihydroxybenzaldehyde, and arachidonoyl dopamine. The antioxidant properties of these compounds at different concentrations (10-30 mu g/mL) were compared with those of reference antioxidants such as BHA, BHT, alpha-tocopherol, and trolox. Each substance showed dose-dependent antioxidant activity. Furthermore, oenin, malvin, arachidonoyl dopamine, callistephin, silychristin, and 3,4-dihydroxy-5-methoxybenzoic acid exhibited more effective antioxidant activity than that observed for the reference antioxidants. These results suggest that these novel compounds may function to protect foods and medicines and to reduce oxidative stress in vivo.
Antioxidant, Antidiabetic, Anticholinergic, and Antiglaucoma Effects of Magnofluorine
(Mdpi, 2022) Durmaz, Lokman; Kiziltas, Hatice; Guven, Leyla; Karagecili, Hasan; Alwasel, Saleh; Gulcin, Ilhami
Magnofluorine, a secondary metabolite commonly found in various plants, has pharmacological potential; however, its antioxidant and enzyme inhibition effects have not been investigated. We investigated the antioxidant potential of Magnofluorine using bioanalytical assays with 2,2-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS(center dot+)), N,N-dimethyl-p-phenylenediamine dihydrochloride (DMPD center dot+), and 1,1-diphenyl-2-picrylhydrazyl (DPPH center dot) scavenging abilities and K-3[Fe(CN)(6)] and Cu2+ reduction abilities. Further, we compared the effects of Magnofluorine and butylated hydroxytoluene (BHT), butylated hydroxyanisole (BHA), alpha-Tocopherol, and Trolox as positive antioxidant controls. According to the analysis results, Magnofluorine removed 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals with an IC50 value of 10.58 mu g/mL. The IC50 values of BHA, BHT, Trolox, and alpha-Tocopherol were 10.10 mu g/mL, 25.95 mu g/mL, 7.059 mu g/mL, and 11.31 mu g/mL, respectively. Our results indicated that the DPPH center dot scavenging effect of Magnofluorine was similar to that of BHA, close to that of Trolox, and better than that of BHT and alpha-tocopherol. The inhibition effect of Magnofluorine was examined against enzymes, such as acetylcholinesterase (AChE), alpha-glycosidase, butyrylcholinesterase (BChE), and human carbonic anhydrase II (hCA II), which are linked to global disorders, such as diabetes, Alzheimer's disease (AD), and glaucoma. Magnofluorine inhibited these metabolic enzymes with Ki values of 10.251.94, 5.991.79, 25.411.10, and 30.563.36 nM, respectively. Thus, Magnofluorine, which has been proven to be an antioxidant, antidiabetic, and anticholinergic in our study, can treat glaucoma. In addition, molecular docking was performed to understand the interactions between Magnofluorine and target enzymes BChE (D: 6T9P), hCA II (A:3HS4), AChE (B:4EY7), and alpha-glycosidase (C:5NN8). The results suggest that Magnofluorine may be an important compound in the transition from natural sources to industrial applications, especially new drugs.
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.
Comprehensive Metabolite Profiling of Berdav Propolis Using Lc-ms/Ms: Determination of Antioxidant, Anticholinergic, Antiglaucoma, and Antidiabetic Effects
(Mdpi, 2023) Karagecili, Hasan; Yilmaz, Mustafa Abdullah; Erturk, Adem; Kiziltas, Hatice; Guven, Leyla; Alwasel, Saleh H.; Gulcin, Ilhami
Propolis is a complex natural compound that honeybees obtain from plants and contributes to hive safety. It is rich in phenolic and flavonoid compounds, which contain antioxidant, antimicrobial, and anticancer properties. In this study, the chemical composition and antioxidant activities of propolis were investigated; ABTS(center dot+), DPPH center dot and DMPD center dot+ were prepared using radical scavenging antioxidant methods. The phenolic and flavonoid contents of propolis were 53 mg of gallic acid equivalent (GAE)/g and 170.164 mg of quercetin equivalent (QE)/g, respectively. The ferric ion (Fe3+) reduction, CUPRAC and FRAP reduction capacities were also studied. The antioxidant and reducing capacities of propolis were compared with those of butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), alpha-tocopherol and Trolox reference standards. The half maximal inhibition concentration (IC50) values of propolis for ABTS(center dot+), DPPH center dot and DMPD center dot+ scavenging activities were found to be 8.15, 20.55 and 86.64 mu g/mL, respectively. Propolis extract demonstrated IC50 values of 3.7, 3.4 and 19.6 mu g/mL against alpha-glycosidase, acetylcholinesterase (AChE) and carbonic anhydrase II (hCA II) enzyme, respectively. These enzymes' inhibition was associated with diabetes, Alzheimer's disease (AD) and glaucoma. The reducing power, antioxidant activity and enzyme inhibition capacity of propolis extract were comparable to those demonstrated by the standards. Twenty-eight phenolic compounds, including acacetin, caffeic acid, p-coumaric acid, naringenin, chrysin, quinic acid, quercetin, and ferulic acid, were determined by LC-MS/MS to be major organic compounds in propolis. The polyphenolic antioxidant-rich content of the ethanol extract of propolis appears to be a natural product that can be used in the treatment of diabetes, AD, glaucoma, epilepsy, and cancerous diseases.
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
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).
Enzyme Inhibition Properties of Calendula Officinalis, Matricaria Chamomilla, and Anthemis Pseudocotula: Kinetics and Molecular Docking Studies
(Acg Publications, 2025) Aslan, Kubra; Kiziltas, Hatice; Guven, Leyla; Karagecili, Hasan; Arslan, Dogan; Gulcin, Ilhami
This study determined the enzyme inhibition potential of three species (Calendula officinalis, Matricaria chamomilla, and Anthemis pseudocotula) from the Asteraceae family through in silico, followed by in vitro studies. Quinic acid, fumaric acid, gallic acid, chlorogenic acid, vanillic acid, quercetin, apigenin, and isorhamnetin were determined by LC-MS/MS in all of the species. Metabolic enzymes are essential catalysts regulating biochemical reactions within living organisms, facilitating energy production, detoxification, and biosynthesis. These enzymes play a crucial role in maintaining cellular homeostasis and are tightly regulated to ensure optimal metabolic function. High docking scores were also obtained for butyrylcholinesterase (BChE), alpha-glycosidase, alpha-amylase, and human carbonic anhydrase I and II enzymes (hCA I and hCA II). Among the extracts, Anthemis pseudocotula was concluded to be the best inhibitor for the enzymes, which was further determined by in vitro enzyme inhibition tests. Besides, it was concluded that all extracts showed anti-cholinergic, anti-diabetic, and anti-glaucoma properties. This is the first study determining the enzyme inhibition property of Anthemis pseudocotula and the three species' hCA I and hCA II inhibition activities.
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 Properties of Some Flavonoids on Carbonic Anhydrase I and Ii Isoenzymes Purified From Human Erythrocytes
(Wiley, 2017) Huyut, Zubeyir; Beydemir, Sukru; Gulcin, Ilhami
Carbonic anhydrases (CAs, E.C.4.2.1.1) play a critical role in many important physiological events and treatment of some diseases. Flavonoids or phenolic compounds have been discovered as novel CAs inhibitors instead of the traditional sulfonamides, with different binding to CAs, pro-drug activities, and new inhibition mechanisms. Here, we investigated the inhibition effects of some flavonoids including malvin, callistephin, oenin, pelargonin, silychristin, and 1-(4-methoxyphenyl)-2-methyl-3-nitro-1-H-indol-6-ol (ID-8) against hCA I and II, which purified from human erythrocytes by affinity column chromatography. Both hCA isoenzymes were inhibited by flavonoids, with IC50 and K-i values in the range of 2.34nM to 346.5M and 51.01-99.55M for hCA I and 86.60-750.00M for hCA II, respectively. These results showed that flavonoids especially malvin and oenin effectively inhibited hCA I and II isoenzymes. Hence, they may be used as an effective CA inhibitor in medical applications for treatment of certain diseases such as glaucoma, in the future.
Inhibitory Effects of Some Phenolic Compounds on the Activities of Carbonic Anhydrase: From in Vivo To Ex Vivo
(Taylor & Francis Ltd, 2016) Huyut, Zubeyir; Beydemir, Sukru; Gulcin, Ilhami
Carbonic anhydrase (CA) inhibitors have been used for more than 60 years for therapeutic purposes in many diseases table such as in medications against antiglaucoma and as diuretics. Phenolic compounds are a new class of CA inhibitor. In our study, we tested the effects of arachidonoyl dopamine, 2,4,6-trihydroxybenzaldehyde and 3,4-dihydroxy-5-methoxybenzoic acid on esterase and the CO2-hydratase activities of CA I and II isozymes purified from in vivo to ex vivo. The K-i values of arachidonoyl dopamine, 2,4,6-trihydroxybenzaldehyde and 3,4-dihydroxy-5-methoxybenzoic acid were 203.80, 1170.00 and 910.00 mu M, respectively for hCA I and 75.25, 354.00 and 1510.00 mu M, respectively for hCA II. Additionally, IC50 values from in vivo studies were found to be in the range of 173.25-1360.0 mu M for CA I and II, respectively, using CO2-hydratase activity methods. These results demonstrated that phenolic compounds used in in vivo studies could be used in different biomedical applications to inhibit approximately 30% of the CO2-hydratase activity of the total CA enzyme of rat erythrocytes.
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).
Lc-Hrms Profiling and Antidiabetic, Anticholinergic, and Antioxidant Activities of Aerial Parts of Kinkor (Ferulago Stellata)
(Mdpi, 2021) Kiziltas, Hatice; Bingol, Zeynebe; Goren, Ahmet Ceyhan; Kose, Leyla Polat; Durmaz, Lokman; Topal, Fevzi; Gulcin, Ilhami
Kinkor (Ferulago stellata) is Turkish medicinal plant species and used in folk medicine against some diseases. As far as we know, the data are not available on the biological activities and chemical composition of this medicinal plant. In this study, the phytochemical composition; some metabolic enzyme inhibition; and antidiabetic, anticholinergic, and antioxidant activities of this plant were assessed. In order to evaluate the antioxidant activity of evaporated ethanolic extract (EEFS) and lyophilized water extract (WEFS) of kinkor (Ferulago stellata), some putative antioxidant methods such as DPPHGreek ano teleia scavenging activity, ABTS(center dot+) scavenging activity, ferric ions (Fe3+) reduction method, cupric ions (Cu2+) reducing capacity, and ferrous ions (Fe2+)-binding activities were separately performed. Furthermore, ascorbic acid, BHT, and alpha-tocopherol were used as the standard compounds. Additionally, the main phenolic compounds that are responsible for antioxidant abilities of ethanol and water extracts of kinkor (Ferulago stellata) were determined by liquid chromatography-high-resolution mass spectrometry (LC-HRMS). Ethanol and water extracts of kinkor (Ferulago stellata) demonstrated effective antioxidant abilities when compared to standards. Moreover, ethanol extract of kinkor (Ferulago stellata) demonstrated IC50 values of 1.772 mu g/mL against acetylcholinesterase (AChE), 33.56 +/- 2.96 mu g/mL against alpha-glycosidase, and 0.639 mu g/mL against alpha-amylase enzyme respectively.
Lc-Hrms Profiling of Phytochemicals, Antidiabetic, Anticholinergic and Antioxidant Activities of Evaporated Ethanol Extract of Astragalus Brachycalyx Fischer
(Acg Publications, 2021) Kiziltas, Hatice; Bingol, Zeynebe; Goren, Ahmet C.; Pinar, Suleyman Mesut; Alwasel, Saleh H.; Gulcin, Ilhami
Astragalus is a perennial plant that has existed for about 2500-3000 years and consists of more than 250 taxonomic parts. Twenty species of Astragalus are endemic to Turkey, as well as the richest genus with 425 taxa. The roots of Asfragalus species are used in folk medicine as hepatoprotective, antioxidant, antibacterial, antihypertensive, antidiabetic and diuretic. Also, it is used to treat diabetes mellitus, leukemia, nephritis and uterine cancer. It is known that in Anatolia, Astragalus roots are traditionally used against leukemia and wound healing. For the purpose, the measuring of antioxidant activity of evaporated ethanol extract of Asfragalus brachycalyx FISCHER (EEAB), some bioanalytic methods including DPPH center dot and ABTS(center dot+) scavenging effects, ferric ions (Fe3+) and cupric ions (Cu2+) reducing abilities, and metal (Fe') chelating activity were realized. alpha-Tocopherol, ascorbic acid, and BHT were used as the standard antioxidants. On the other hand, some phenolic compounds, which responsible for antioxidant activities of EEAB was determined by liquid chromatography-high resolution mass spectrometry (LC-HRMS). At the similar concentration, EEAB exhibited efficient antioxidant effects when compared to standard compounds. Additionally, EEAB showed IC50 values of 1.985 mu g/mL toward acetylcholinesterase (AChE), 0.620 mu g/mL on alpha-glycosidase and 0.306 mu g/mL against alpha-amylase enzymes.
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
Mono- or Di-Substituted Imidazole Derivatives for Inhibition of Acetylcholine and Butyrylcholine Esterases
(Academic Press inc Elsevier Science, 2019) Kuzu, Burak; Tan, Meltem; Taslimi, Parham; Gulcin, Ilhami; Taspinar, Mehmet; Menges, Nurettin
Mono- or di-substituted imidazole derivatives were synthesized using a one-pot, two-step strategy. All imidazole derivatives were tested for AChE and BChE inhibition and showed nanomolar activity similar to that of the test compound donepezil and higher than that of tacrine. Structure activity relationship studies, docking studies to on X-ray crystal structure of AChE with PDB code 1B41, and adsorption, distribution, metabolism, and excretion (ADME) predictions were performed. The synthesized core skeleton was bound to important regions of the active site of AChE such as the peripheral anionic site (PAS), oxyanion hole (OH), and anionic subsite (AS). Selectivity of the reported test compounds was calculated and enzyme kinetic studies revealed that they behave as competitive inhibitors, while two of the test compounds showed noncompetitive inhibitory behavior. ADME predictions revealed that the synthesized molecules might pass through the blood brain barrier and intestinal epithelial barrier and circulate freely in the blood stream without binding to human serum albumin. While the toxicity of one compound on the WS1 (skin fibroblast) cell line was 1790 mu M, its toxicity on the SH-SY5Y (neuroblastoma) cell line was 950 mu M.