Publications by authors named "Fikret Türkan"

39 Publications

Enzyme inhibitory function and phytochemical profile of Inula discoidea using in vitro and in silico methods.

Biophys Chem 2021 Jun 5;277:106629. Epub 2021 Jun 5.

Department of Plant Sciences, Quaid-i-Azam University Islamabad, Islamabad, Pakistan.

Many plant species have a large diversity of secondary metabolites with different biological activities. This study aims to assess the phenolic constituent, enzyme inhibitory and antioxidant activities of the aqueous (water) and methanol extracts of Inula discoidea. The enzyme assays showed effective enzyme inhibition of the methanol extract against acetylcholinesterase (AChE), butyrylcholinesterase (BChE), glutathione S-transferase (GST), and α-glycosidase (α-Gly) enzymes. The IC values for AChE, BChE, GST, and α-Gly were found as 38.5 mg/mL, 34.65 mg/mL, 77.0 mg/mL, and 40.76 mg/mL, respectively. Antioxidant properties of the aqueous and methanol extracts of I. discoidea were determined by four well-known in vitro techniques (ABTS, CUPRAC, DPPH, and FRAP methods). The antioxidant values of both water and methanol extracts were found to be better than the standard antioxidants (BHA, BHT, ascorbic acid, and α-tocopherol) in ABTS and CUPRAC methods. According to an updated LC-MS/MS technique analysis, quinic acid (21.08 mg/g), protocatechuic acid (4.49 mg/g), and gallic acid (0.48 mg/g) were found as major phenolic compounds of the plant extract. The binding interactions of major phenolic compounds of I. discoidea with the AChE, BChE, GST, and α-Gly enzymes were investigated by the molecular docking studies.
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http://dx.doi.org/10.1016/j.bpc.2021.106629DOI Listing
June 2021

Transition metal complexes of a multidentate Schiff base ligand containing pyridine: synthesis, characterization, enzyme inhibitions, antioxidant properties, and molecular docking studies.

Biometals 2021 Apr 2;34(2):393-406. Epub 2021 Feb 2.

Department of Pharmaceutical Chemistry, SPP School of Pharmacy & Technology Management, SVKM's NMIMS, Mumbai, 400 056, India.

A series of Fe(II), Ni(II), and Pd(II) complexes were prepared with a novel Schiff base ligand containing pyridine moiety. The prepared compounds were characterized using FT-IR, H and  C NMR, UV-Vis, powder XRD, thermogravimetric analysis, mass spectra, magnetic susceptibility, and elemental analysis. The coordination geometry of Fe(II) and Ni(II) complexes were octahedral, where Fe(II) and Ni(II) metal ions were coordinated by an oxygen atom of the carbonyl group, a nitrogen atom of the azomethine moiety, and a phenolic oxygen atom. The Pd(II) complex had square planar geometry. All of the synthesized compounds were tested for their biochemical properties, including enzyme inhibition and antioxidant activities. According to the in vitro DPPH and FRAP antioxidant methods, the Schiff base ligand and its Fe(II)/Pd(II) complexes showed close antioxidant activities against the standards (BHA, BHT, ascorbic acid, and α-tocopherol). Enzyme inhibitions of the metal complexes were investigated against glutathione S-transferase (GST), acetylcholinesterase (AChE), and butyrylcholinesterase (BChE) enzymes. The best inhibition value (K) was observed for the Ni(II) complex against GST (2.63 ± 0.04 µM). Also, the Pd(II) complex showed the best inhibition value (10.17 ± 1.88 µM) against AChE. Molecular docking specified significant interactions at the active pockets of respective target enzymes. The Ni(II) complex exhibited good binding affinity against both BChE (- 9.0 kcal/mol and 9.36 ± 2.03 µM) and GST (- 7.0 kcal/mol and 2.63 ± 0.04 µM) enzymes.
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http://dx.doi.org/10.1007/s10534-021-00287-zDOI Listing
April 2021

Synthesis of novel 1,2,3 triazole derivatives and assessment of their potential cholinesterases, glutathione S-transferase enzymes inhibitory properties: An in vitro and in silico study.

Bioorg Chem 2021 Feb 31;107:104606. Epub 2020 Dec 31.

Department of Chemistry, Faculty of Sciences, Karadeniz Technical University, 61080 Trabzon, Turkey.

In this study, new 1,2,3-triazole derivatives containing chalcone core (1-7) were synthesized. Obtained compounds were characterized by IR, H NMR, C NMR, and mass studies. Characterized compounds (1-7) inhibitory effects were tested against the glutathione S-transferase (GST), acetylcholinesterase (AChE), and Butyrylcholinesterase (BChE). Their K values were in the range of 5.88-11.13 µM on AChE, 5.08-15.12 µM on BChE, and 9.82-13.22 µM on GST. Remarkable inhibitory effects were obtained against three tested metabolic enzymes. Also, binding scores of the best-inhibitors against AChE, BChE, and GST enzymes were detected as -9.969 kcal/mol, -10.672 kcal/mol, and -8.832 kcal/mol, respectively. Isoindoline-1,3-dione and benzothiophene moieties played a critical role in the inhibition of AChE and BChE enzymes, respectively. Phenylene and triazole moieties had the most important interactions for inhibition of the GST enzyme. Therefore, in vivo and in silico results indicated that these compounds can be considered in drug design processes for the treatment of some diseases including Alzheimer's disease (AD), leukemia, and some type of cancer.
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http://dx.doi.org/10.1016/j.bioorg.2020.104606DOI Listing
February 2021

Synthesis, design, and assessment of novel morpholine-derived Mannich bases as multifunctional agents for the potential enzyme inhibitory properties including docking study.

Bioorg Chem 2021 Feb 3;107:104524. Epub 2020 Dec 3.

Department of Chemistry, Faculty of Science and Letters, Kafkas University, Kars 36100, Turkey.

The synthesized Schiff Bases were reacted with formaldehyde and secondary amine such as 2,6-dimethylmorpholine to afford N-Mannich bases through the Mannich reaction. 3-Substitued-4-(4-hydroxybenzylidenamino)-4,5-dihydro-1H-1,2,4-triazol-5-ones (4) were treated with 2,6-dimethylmorpholine in the presence of formaldehyde to synthesize eight new 1-(2,6-dimethylmorpholino-4-yl-methyl)-3-substitued-4-(4-hydroxybenzylidenamino)-4,5-dihydro-1H-1,2,4-triazol-5-ones (4a-h). The structures of the synthesized eight new compounds were characterized using IR, H NMR, C NMR, and HR-MS spectroscopic methods. Synthesized compounds inhibitory activity determined against the acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and glutathione S-transferase (GST) enzymes with Ki values in the range 25.23-42.19 µM for AChE, 19.37-34.22 µM for BChE, and 21.84-41.14 µM for GST, respectively. Binding scores of most active inhibitors against AChE, BChE, and GST enzymes were detected as -10.294 kcal/mol, -9.562 kcal/mol, and -7.112 kcal/mol, respectively. The hydroxybenzylidene moiety of the most active inhibitors caused to inhibition of the enzymes through hydrophobic interaction and hydrogen bond.
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http://dx.doi.org/10.1016/j.bioorg.2020.104524DOI Listing
February 2021

Comparison of the protective effects of curcumin and caffeic acid phenethyl ester against doxorubicin-induced testicular toxicity.

Andrologia 2020 Dec 1:e13919. Epub 2020 Dec 1.

Medical Faculty, Department of Pediatric Surgery, Van Yuzuncu Yıl University, Van, Turkey.

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 µL), 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.
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http://dx.doi.org/10.1111/and.13919DOI Listing
December 2020

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

Synthesis, characterization, powder X-ray diffraction analysis, thermal stability, antioxidant properties and enzyme inhibitions of M(II)-Schiff base ligand complexes.

J Biomol Struct Dyn 2020 Aug 5:1-8. Epub 2020 Aug 5.

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

The Schiff base ligand (()-6-methyl-2-(2,3,4-trimethoxybenzylideneamino)-4,5,6,7-tetrahydrobenzo[]thiophene-3-carbonitrile) and its cobalt(II) and palladium(II) complexes were successfully prepared. The structure of the compounds was elucidated by various techniques (NMR, FT-IR, powder X-ray diffraction, microanalysis, TGA, magnetic susceptibility, mass spectrometry). The Pd(II) complex showed a square planar geometry and the Co(II) complex had an octahedral geometry. ABTS (2,2-azino-bis 3-ethylbenzothiazloine-6-sulphonic acid), DPPH (1,1-diphenyl-2-picrylhydrazyl), FRAP (ferric-reducing antioxidant power) and CUPRAC (cupric reducing antioxidant capacity) methods were applied to identify the antioxidant features of the synthesized compounds. In addition, glutathione S-transferase and acetyl/butyryl cholinesterase enzymes were examined for possible inhibition capacities of the complexes. According to the enzyme activity measurements, Ru(II) complex inhibited both GST and BChE enzymes, while Fe(II) complex inhibited only AChE enzyme. Furthermore, the antioxidant activities and enzyme inhibitions of the previously synthesized Fe(II) and Ru(II) complexes of the same ligand were examined to make a comparison of the metal complexes.Communicated by Ramaswamy H. Sarma.
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http://dx.doi.org/10.1080/07391102.2020.1802340DOI Listing
August 2020

Benzenesulfonamide derivatives as potent acetylcholinesterase, α-glycosidase, and glutathione S-transferase inhibitors: biological evaluation and molecular docking studies.

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

Department of Biochemistry, Faculty of Pharmacy, Anadolu University, Eskişehir, Turkey.

Sulfonamide derivatives exhibit a wide biological activity and can function as potential medical molecules in the development of a drug. Studies have reported that the compounds have an effect on many enzymes. In this study, the derivatives of amine sulfonamide (-) were prepared with reduced imine compounds (-) with NaBH in methanol. The synthesized compounds were fully characterized by spectral data and analytical. The effect of the synthesized derivatives on acetylcholinesterase (AChE), glutathione S-transferase (GST) and α-glycosidase (α-GLY) enzymes were determined. For the AChE and α-GLY, the most powerful inhibition was observed on and series with value in the range 2.26 ± 0.45-3.57 ± 0.97 and 95.73 ± 13.67-102.45 ± 11.72 µM, respectively. values of the series for GST were found in the range of 22.76 ± 1.23-49.29 ± 4.49. Finally, the compounds have a stronger inhibitor in lower concentrations by the attachment of functional electronegative groups such as two halogens (-Br and -CI), -OH to the benzene ring and -SONH. The crystal structures of AChE, α-GLY, and GST in complex with selected derivatives and show the importance of the functional moieties in the binding modes within the receptors.Communicated by Ramaswamy H. Sarma.
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http://dx.doi.org/10.1080/07391102.2020.1790422DOI Listing
July 2020

Novel benzo[b]xanthene derivatives: Bismuth(III) triflate-catalyzed one-pot synthesis, characterization, and acetylcholinesterase, glutathione S-transferase, and butyrylcholinesterase inhibitory properties.

Arch Pharm (Weinheim) 2020 Aug 26;353(8):e2000030. Epub 2020 May 26.

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

In this study, 3,4-dihydro-12-aryl-1H-benzo[b]xanthene-1,6,11-(2H,12H)trione compounds were obtained through one-pot condensation of various substituted aromatic aldehydes, 2-hydroxy-1,4-naphthoquinone, and dimedone in the presence of Bi(OTf) as a green and reusable catalyst. The structural characterization of these novel substituted benzo[b]xanthenes was performed by spectroscopic methods, and their inhibitory actions against butyrylcholinesterase (BChE), acetylcholinesterase (AChE), and glutathione S-transferase (GST) were investigated. GST is an enzyme responsible for removing toxic molecules during Phase II reactions in the detoxification mechanism. The AChE and BChE enzymes, which are called cholinesterases, are among the enzymes that occur especially during dementia such as brain damage or Alzheimer's disease. Inhibition effects of the benzo[b]xanthene derivatives on AChE, BChE, and GST were found at the millimolar level. The best inhibitor for GST is compound 4a (31.18 ± 6.13 mM), for AChE, it is compound 4d (28.16 ± 3.46 mM), and for BChE, it is compound 4f (36.24 ± 3.19 mM). Compound 4a inhibited the dimerization of GST subunits, and compounds 4d and 4f directly inhibited the catalytic activity by interacting with the catalytic active site or a related site of the AChE and BChE enzymes, respectively.
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http://dx.doi.org/10.1002/ardp.202000030DOI Listing
August 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 2021 Jul 4;39(10):3693-3702. 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
July 2021

Inhibition effects of isoproterenol, chlorpromazine, carbamazepine, tamoxifen drugs on glutathione S-transferase, cholinesterases enzymes and molecular docking studies.

J Biomol Struct Dyn 2021 Jun 13;39(9):3277-3284. Epub 2020 May 13.

Department of Molecular Biology and Genetics, Faculty of Arts and Science, Kilis 7 Aralik University, Kilis, Turkey.

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.
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http://dx.doi.org/10.1080/07391102.2020.1763200DOI Listing
June 2021

Cholinesterases, α-glycosidase, and carbonic anhydrase inhibition properties of 1H-pyrazolo[1,2-b]phthalazine-5,10-dione derivatives: Synthetic analogues for the treatment of Alzheimer's disease and diabetes mellitus.

Bioorg Chem 2020 04 1;97:103647. Epub 2020 Feb 1.

Atatürk University, Faculty of Science, Department of Chemistry, 25240 Erzurum, Turkey.

In this study, using the Cu(OTf) catalyst, 1H-pyrazolo[1,2-b]phthalazine-5,10-dione derivative molecules were carried out in one step and with high yield (86-91%). The previously synthesized 1H-pyrazolo[1,2-b]phthalazine-5,10-dione derivatives, carbonic anhydrase I and II isozymes (hCA I and II), acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and α-glycosidase (α-Gly) enzymes with K values in the range of 4.88-15.94 nM for hCA I, 7.04-20.83 nM for hCA II, 68.25-158.27 for AChE, 60.17-91.27 for BChE and 0.36-2.36 nM for α-Gly, respectively. In silico studies were performed on the molecules inhibiting hCA I, hCA II, AChE, BChE and α-Gly receptors. When we evaluated the data obtained in this work, we determined the inhibition type of the 1H-pyrazolo[1,2-b]phthalazine-5,10-dione derivatives at the receptors. Reference inhibitors were used for all enzymes.
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http://dx.doi.org/10.1016/j.bioorg.2020.103647DOI Listing
April 2020

Toxicological effects of some antiparasitic drugs on equine liver glutathione S-Transferase enzyme activity.

J Pharm Biomed Anal 2020 Feb 17;180:113048. Epub 2019 Dec 17.

Sen Research Group, Biochemistry Department, Faculty of Arts and Science, Dumlupinar University, 43100, Kutahya, Turkey. Electronic address:

Benzimidazoles are antiparasitic drugs having an extensive application field like agriculture, medicine, and especially in veterinary medicine. In this study, we report the effect of some benzimidazole drugs such as ricobendazole (RBZ), thiabendazole (TBZ), albendazole (ALBA) and oxfendazole (OFZ) on glutathione s-transferase (GST) enzyme activity. The kinetics studies, IC and Ki values of the tested drugs on GSTs enzyme activity were investigated. The obtained ranking of IC values were found to be approximately RBZ (53.31 μM, r 0.9778) < OFZ (57.75 μM, r 0.9630) < ALBA (63.00 μM, r 0.9443) < TBZ (69.30 μM, r 0.9491). And the obtained ranking of Ki values of the tested drugs (RBZ, TBZ, ALBA, and OFZ) for GSTs enzyme activity was found to be approximately 26.37 ± 2.96, 44.01 ± 5.74, 39.82 ± 3.98 and 30.14 ± 3.03 μM, respectively. Experimental results showed that tested the benzimidazoles drugs have some significant inhibitory effect on GSTs enzyme activity. And also, it was determined that RBZ, ALBA, OFZ are competitive inhibition, but TBZ is non-competitive inhibitors on GSTs enzyme activity. RBZ drug showed the best inhibitory effect with the lowest Ki value.
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http://dx.doi.org/10.1016/j.jpba.2019.113048DOI Listing
February 2020

ICP-MS and HPLC analyses, enzyme inhibition and antioxidant potential of Achillea schischkinii Sosn.

Bioorg Chem 2020 01 1;94:103333. Epub 2019 Oct 1.

Department of Nursing, School of Health, Mus Alparslan University, Mus, Turkey. Electronic address:

Achillea schischkinii Sosn. is an endemic plant species and it belongs to Asteraceae family. It is distributed widely in the Central and East Anatolia. This study was carried out for evaluation of the antioxidant activity, enzyme inhibition effect, elemental and phenolic content of A. schischkinii. Briefly, acetylcholinesterase (AChE), butyrylcholinesterase (BChE), α-glycosidase (α-Gly), and glutathione S-transferase (GST) enzymes were strongly inhibited by A. schischkinii. IC values for AChE, BChE, α-Gly, and GST enzymes were found as 19.3 mg/mL, 15.4 mg/mL, 69.3 mg/mL, and 34.7 mg/mL respectively. The antioxidant activity of the sample was evaluated by four different in vitro bioanalytical methods. Besides, the concentrations of twelve elements in A. schischkinii were analyzed by ICP-MS technique. Zn (50.6 ppm), Mn (23.0 ppm), and Cu (12.7 ppm) were found as major elements. Furthermore, catechin (20.8 µg/mg extract), trans-ferulic acid (18.3 µg/mg extract), and gallic acid (11.2 µg/mg extract) were characterized as major phenolic compounds by using HPLC. PRACTICAL APPLICATIONS: Acetylcholinesterase, butyrylcholinesterase, α-glycosidase, and glutathione s-transferase enzymes have crucial functions on metabolism. Enzyme inhibition or activation mostly attributed to some health disorders such as Alzheimer's disease, Diabetes mellitus, cancer and hyperglycemia. Phenolic contents are responsible for effective biological activity. This study evaluated the phenolic content and antioxidant activity of Achillea schischkinii as well as the inhibition effect against four metabolic enzymes. The results would be beneficial for using the plant in the food industry and pharmacological process.
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http://dx.doi.org/10.1016/j.bioorg.2019.103333DOI Listing
January 2020

Pyrazole[3,4-d]pyridazine derivatives: Molecular docking and explore of acetylcholinesterase and carbonic anhydrase enzymes inhibitors as anticholinergics potentials.

Bioorg Chem 2019 11 20;92:103213. Epub 2019 Aug 20.

Sen Research Group, Biochemistry Department, Faculty of Arts and Science, Dumlupınar University, Evliya Çelebi Campus, 43100 Kütahya, Turkey. Electronic address:

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 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.
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http://dx.doi.org/10.1016/j.bioorg.2019.103213DOI Listing
November 2019

Phytochemical Content, Antidiabetic, Anticholinergic, and Antioxidant Activities of Endemic Lecokia cretica Extracts.

Chem Biodivers 2019 Oct 18;16(10):e1900341. Epub 2019 Sep 18.

Department of Chemistry, Faculty of Science, Erzincan University, 26100, Erzincan, Turkey.

The aim of this work was to investigate the enzyme inhibition, antioxidant activity, and phenolic compounds of Lecokia cretica (Lam.) DC. Acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and α-glycosidase enzymes were strongly inhibited by the L. cretica extracts. IC values for the three enzymes were found as 3.21 mg/mL, 2.1 mg/mL, and 2.07 mg/mL, respectively. Antioxidant activities were examined in both aqueous and ethanol (EtOH) extracts using CUPRAC, FRAP, and DPPH method. Also, the phenolic compounds of the endemic plant were identified and quantified by using HPLC/MS/MS. According to the results, the extracts have remarkable antioxidant activities. The most abundant phenolic acids of L. cretica in EtOH extract were determined as quinic acid (12.76 mg/kg of crude extract), chlorogenic acid (3.39 mg/kg), and malic acid (2.38 mg/kg).
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http://dx.doi.org/10.1002/cbdv.201900341DOI Listing
October 2019

In vivo biochemical evaluations of some β-lactam group antibiotics on glutathione reductase and glutathione S- transferase enzyme activities.

Life Sci 2019 Aug 14;231:116572. Epub 2019 Jun 14.

Tuzluca Vocational School, Igdır University, Igdır, Turkey.

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 × 6) were created from these rats, divided to another 4 groups (4 × 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.
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http://dx.doi.org/10.1016/j.lfs.2019.116572DOI Listing
August 2019

Spectroscopic and Structural Characterization, Enzyme Inhibitions, and Antioxidant Effects of New Ru(II) and Ni(II) Complexes of Schiff Base.

Chem Biodivers 2019 Aug 18;16(8):e1900243. Epub 2019 Jul 18.

Department of Nursing, School of Health, Muş Alparslan University, 49250, Muş, Turkey.

The new complex compounds [RuLCl(p-cymene)] ⋅ 3H O and [NiL (H O) ] ⋅ 3H O (L: 1-{4-[(2-hydroxy-3-methoxybenzylidene)amino]phenyl}ethanone) were prepared and characterized using FT-IR, H- and C-NMR, mass spectroscopy, TGA, elemental analysis, X-ray powder diffraction and magnetic moment techniques. Octahedral geometry for new Ni(II) and Ru(II) complexes was proposed. Thermal decomposition confirmed the existence of lattice and coordinated water molecule in the complexes. To determine the antioxidant properties of Schiff base ligand and its Ni(II), Ru(II) metal complexes, FRAP, CUPRAC, ABTS and DPPH methods of antioxidant assays were used. Moreover, enzyme inhibition of complexes was evaluated against carbonic anhydrase I and II isoenzymes (CA I and CA II) and acetylcholinesterase (AChE). For CA I and CA II, the best inhibition enzymes, was the Ni(II) complex with 62.98±18.41, 86.17±23.62 Ki values, whereas this inhibition effect showed ligand with 24.53±2.66 Ki value for the AChE enzyme.
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http://dx.doi.org/10.1002/cbdv.201900243DOI Listing
August 2019

Investigation of the toxicological and inhibitory effects of some benzimidazole agents on acetylcholinesterase and butyrylcholinesterase enzymes.

Authors:
Fikret Türkan

Arch Physiol Biochem 2021 Apr 28;127(2):97-101. Epub 2019 May 28.

Health Services Vocational School, Igdır University, Igdır, Turkey.

Benzimidazole, an anthelmintic used in the manufacture of human and veterinary drugs, is an important heterocyclic compound. In this work, I investigated the effect of drugs such as ricobendazole, thiabendazole, albendazole, and oxfendazole, on Acetylcholinesterase (AChE) and Butyrylcholinesterase (BChE) enzyme activity. As kinetic studies, K and IC values were calculated separately for each drug, respectively. Study findings have shown that benzimidazoles inhibit both AChE and BChE enzymes at the nanomolar level. The compound that best was inhibited the AChE enzyme ricobendazole, and it was that the best inhibited the BChE enzyme thiabendazole. IC and K values were calculated 123.02 nM, 28.68 ± 8.46 nM for AChE and 64.26 nM, 12.08 ± 2.18 nM for BChE respectively. The types of inhibition indicated by the drugs were investigated and they were found to show non-competitive inhibition.
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http://dx.doi.org/10.1080/13813455.2019.1618341DOI Listing
April 2021

Synthesis, characterization, molecular docking and biological activities of novel pyrazoline derivatives.

Arch Pharm (Weinheim) 2019 Jun 24;352(6):e1800359. Epub 2019 May 24.

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

In this study, synthesis of ethyl 2-((4-bromophenyl)diazenyl)-3-oxo-phenylpropanoate 1 was carried out and a series of new 3H-pyrazol-3-ones (P1-7) were synthesized from 1 as well as various hydrazines. The obtained yields of the synthesized compounds were moderate (40-70%) and these compounds were confirmed by spectral data. These novel pyrazoline derivatives were effective inhibitor compounds of the human carbonic anhydrase I and II isozymes (hCAs I and II) and of the acetylcholinesterase (AChE) enzyme, with K values in the range of 17.4-40.7 nM for hCA I, 16.1-55.2 nM for hCA II, and 48.2-84.1 nM for AChE. In silico studies were performed on the compounds inhibiting hCA I, hCA II, and AChE receptors. On the basis of the findings, the inhibition profile of the new pyrazoline compounds at the receptors was determined.
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http://dx.doi.org/10.1002/ardp.201800359DOI Listing
June 2019

Influence of some β-lactam drugs on selected antioxidant enzyme and lipid peroxidation levels in different rat tissues.

Drug Chem Toxicol 2020 Jan 7;43(1):27-36. Epub 2019 May 7.

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

Antioxidant enzymes play an important role in body defense and free radical removal. Cephalosporins are β-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 ( = 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 ( < 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.
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http://dx.doi.org/10.1080/01480545.2019.1608230DOI Listing
January 2020

Purification and characterization of glutathione S-transferase from blueberry fruits ( L.) and investigated of some pesticide inhibition effects on enzyme activity.

Heliyon 2019 Apr 10;5(4):e01422. Epub 2019 Apr 10.

Sen Research Group, Department of Biochemistry, Faculty of Arts and Science, Dumlupınar University, Evliya Çelebi Campus, 43100, Kütahya, Turkey.

Pesticides cause pollution by remaining in water, soil, fruits and vegetables for a long time and also reach human through the food chain. It was thought that some pesticides used in agriculture could adversely affect the antioxidant enzyme system and the minimum inhibition values were studied. glutathione s-transferase (GST), an important antioxidant enzyme, catalyzes the conjugation of glutathione with toxic metabolites. It was purified from the blueberry fruits. The purification of the enzyme was performed separately by affinity and gel filtration chromatography. The purity of the enzyme was determined by SDS-PAGE electrophoresis. Characterization studies were done for the enzyme. For this purpose, optimal pH, temperature, K and V values for GSH and CDNB were also determined for the enzyme as 7.2 in K-phosphate buffer, 50 °C, 1.0 M, 7.0 in K-phosphate buffer, 1.57 mM; 0.17 mM and 0.048 EU/mL, 0.0159 EU/mL, respectively. Additionally, inhibitory effects of some pesticides; dichlorvos, acetamiprid, cyhalothrin, haloxyfop-p-Methyl, 2,4 dichlorophenoxy acetic acid, cypermethrin, imidacloprid, fenoxaprop-p-ethyl, glyphosate isopropylamine salt were examined the enzyme activity by performing Lineweaver-Burk graphs and plotting activity % IC and K values were calculated for each of pesticides. All of the pesticides inhibited the GST enzyme at millimolar level. Pesticide showing the best inhibitory effect was found as dichlorvos. The Ki value which is the inhibition constant of this pesticide was 0.0175 ± 0.005.
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http://dx.doi.org/10.1016/j.heliyon.2019.e01422DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6460380PMC
April 2019

Tannic acid as a natural antioxidant compound: Discovery of a potent metabolic enzyme inhibitor for a new therapeutic approach in diabetes and Alzheimer's disease.

J Biochem Mol Toxicol 2019 Aug 11;33(8):e22340. Epub 2019 Apr 11.

Department of Pharmacognosy, Faculty of Pharmacy, Anadolu University, Eskisehir, Turkey.

Multiple studies have been recorded on the synthesis and design of multi-aim anti-Alzheimer molecules. Using dual butyrylcholinesterase/acetylcholinesterase inhibitor molecules has attracted more interest in the therapy for Alzheimer's disease. In this study, a tannic acid compound showed excellent inhibitory effects against acetylcholine esterase (AChE), α-glycosidase, α-amylase, and butyrylcholinesterase (BChE). IC values of tannic acid obtained 11.9 nM against α-glycosidase and 3.3 nM against α-amylase, respectively. In contrast, K values were found of 50.96 ± 2.18 µM against AChE and 53.17 ± 4.47 µM against BChE. α-Glycosidase inhibitor compounds can be utilized as a novel group of antidiabetic drugs. By competitively decreasing glycosidase activity, these inhibitor molecules help to hamper the fast breakdown of sugar molecules and thereby control the blood sugar level.
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http://dx.doi.org/10.1002/jbt.22340DOI Listing
August 2019

Synthesis, biological evaluation and molecular docking of novel pyrazole derivatives as potent carbonic anhydrase and acetylcholinesterase inhibitors.

Bioorg Chem 2019 05 5;86:420-427. Epub 2019 Feb 5.

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

A series of substituted pyrazole compounds (1-8 and 9a, b) were synthesized and their structure was characterized by IR, NMR, and Mass analysis. These obtained novel pyrazole derivatives (1-8 and 9a, b) were emerged as effective inhibitors of the cytosolic carbonic anhydrase I and II isoforms (hCA I and II) and acetylcholinesterase (AChE) enzymes with K values in the range of 1.03 ± 0.23-22.65 ± 5.36 µM for hCA I, 1.82 ± 0.30-27.94 ± 4.74 µM for hCA II, and 48.94 ± 9.63-116.05 ± 14.95 µM for AChE, respectively. Docking studies were performed for the most active compounds, 2 and 5, and binding mode between the compounds and the receptors were determined.
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http://dx.doi.org/10.1016/j.bioorg.2019.02.013DOI Listing
May 2019

Synthesis and characterization of novel substituted thiophene derivatives and discovery of their carbonic anhydrase and acetylcholinesterase inhibition effects.

J Biochem Mol Toxicol 2019 Mar 10;33(3):e22261. Epub 2018 Dec 10.

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

Novel substituted thiophene derivatives (1, 2a-e, 3, and 4) were synthesized and their structures were characterized by infrared radiation, nuclear magnetic resonance, and mass analysis. These novel substituted thiophene derivatives were effective inhibitor compounds of the carbonic anhydrase I and II isozymes (hCA I and II), and acetylcholinesterase (AChE) enzyme with K values in the range of 447.28 to 1004.65 nM for hCA I, 309.44 to 935.93 nM for hCA II, and 0.28 to 4.01 nM for AChE, respectively. Novel substituted thiophene derivatives can be good candidate drugs for the treatment of some diseases like neurological disorders, epilepsy, glaucoma, gastric and duodenal ulcers, mountain sickness, or osteoporosis as carbonic anhydrase isozymes inhibitors, and for the treatment of Alzheimer's and Parkinson's diseases as acetylcholinesterase inhibitors.
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http://dx.doi.org/10.1002/jbt.22261DOI Listing
March 2019

Some pyrazoles derivatives: Potent carbonic anhydrase, α-glycosidase, and cholinesterase enzymes inhibitors.

Arch Pharm (Weinheim) 2018 Oct 23;351(10):e1800200. Epub 2018 Sep 23.

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

A series of substituteed pyrazol-4-yl-diazene derivatives were found to be effective inhibitors against α-glycosidase, cytosolic carbonic anhydrase I and II isoforms (hCA I and II), butyrylcholinesterase (BChE), and acetylcholinesterase (AChE) with K values in the range of 33.72 ± 7.93 to 90.56 ± 27.52 nM for α-glycosidase, 1.06 ± 0.16 to 9.83 ± 0.74 nM for hCA I, 0.68 ± 0.12 to 7.16 ± 1.14 nM for hCA II, 44.66 ± 10.06 to 78.34 ± 17.83 nM for AChE, and 50.36 ± 13.88 to 88.36 ± 20.03 nM for BChE, respectively. Recently, inhibition of these metabolic enzymes has been considered as a promising factor for pharmacologic intervention in a diversity of disturbances, such as diabetes, glaucoma, obesity, epilepsy, cancer, and neurodegenerative diseases.
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http://dx.doi.org/10.1002/ardp.201800200DOI Listing
October 2018

Investigation of the effects of cephalosporin antibiotics on glutathione S-transferase activity in different tissues of rats conditions in order to drug development research.

Drug Chem Toxicol 2020 Jul 11;43(4):423-428. Epub 2018 Sep 11.

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

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 ( < .05). In kidney tissues, it was lower than the same control group the cefuroxime and cefoperazone groups at 7th hours ( < .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 ( < .05).
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http://dx.doi.org/10.1080/01480545.2018.1497644DOI Listing
July 2020

The toxicological impact of some avermectins on human erythrocytes glutathione S-transferase enzyme.

J Biochem Mol Toxicol 2018 Oct 8;32(10):e22205. Epub 2018 Aug 8.

Department of Treatment and Rehabilitation, Tuzluca Vocational School, Igdır University, Igdır, Turkey.

The drugs of the class avermectins are antiparasitic agents, which are widely used in medical and agricultural fields, especially in veterinary medicine. The aim of this study was to investigate the inhibitory effects of avermectin derivatives such as abamectin, doramectin, eprinomectin, ivermectin, and moxidectin, which are used for internal and external mammalian parasites. Glutathione S-transferase (GST, E.C. 2.5.1.18) was purified from fresh human erythrocytes. The purification of the GST enzyme was performed separately by affinity chromatography with a yield of 34.81% and 117.94-fold purification. The control of the pure GST enzyme was performed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis, and a single band was obtained. The IC values were approximately 0.31, 0.39, 0.13, 0.44, and 0.73 mM for abamectin, doramectin, eprinomectin, ivermectin, and moxidectin, and the K values were 0.32 ± 0.06, 0.39 ± 0.09, 0.13 ± 0.03, 0.44 ± 0.02, 0.73 ± 0.04 mM, respectively. This data revealed that the tested avermectins showed significant inhibitory effects on the GST enzyme.
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http://dx.doi.org/10.1002/jbt.22205DOI Listing
October 2018

Antidiabetic and antiparasitic potentials: Inhibition effects of some natural antioxidant compounds on α-glycosidase, α-amylase and human glutathione S-transferase enzymes.

Int J Biol Macromol 2018 Nov 1;119:741-746. Epub 2018 Aug 1.

Sen Research Group, Department of Biochemistry, Faculty of Arts and Science, Dumlupınar University, Evliya Çelebi Campus, 43100 Kütahya, Turkey. Electronic address:

The glutathione S-transferase (GST) was purified from fresh blood erythrocytes using affinity column chromatography. Also, α-amylase from porcine pancreas and α-glycosidase from Saccharomyces cerevisiae were used as target enzymes. In this study, these compounds were tested on α-amylase, α-glycosidase, and GST enzymes and demonstrated effective inhibitor compounds with K values in the range of 8.34-40.78 μM against GST, and 120.53-892.36 nM against α-glycosidase. Additionally, the phenolic molecules were tested for the inhibition of α-amylase enzyme which determined effective inhibition profile with IC values in the range of 175.01-626.58 nM. Indeed, these molecules can be elective inhibitors of GST, α-glycosidase and α-amylase enzymes as antidiabetic and antiparasitic agents.
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http://dx.doi.org/10.1016/j.ijbiomac.2018.08.001DOI Listing
November 2018

Synthesis, crystal structure and biological evaluation of spectroscopic characterization of Ni(II) and Co(II) complexes with N-salicyloil-N'-maleoil-hydrazine as anticholinergic and antidiabetic agents.

J Biochem Mol Toxicol 2018 Sep 25;32(9):e22197. Epub 2018 Jul 25.

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

[Ni(C H N O ) (H O) ]•3(C H NO) (1) and [Co(C H N O ) (H O) ]•3(C H NO) (2) are synthesized and characterized by elemental analysis, FT-IR spectra, magnetic susceptibility, and thermal analysis. In addition, the crystal structure of Ni(II) complex is presented. Both complexes show distorted octahedral geometry. In 1 and 2, metal ions are coordinated by two oxygen atoms of salicylic residue and two nitrogen atoms of maleic amide residue from two ligands, and two oxygen atoms from two water molecules. In this paper, both compounds showed excellent inhibitory effects against human carbonic anhydrase (hCA) isoforms I, and II, α-glycosidase, acetylcholinesterase (AChE), and butyrylcholinesterase (BChE). Compounds 1 and 2 had Ki values of 18.36 ± 4.38 and 26.61 ± 7.54 nM against hCA I and 13.81 ± 3.02 and 29.56 ± 6.52 nM against hCA II, respectively. On the other hand, their Ki values were found to be 487.45 ± 54.18 and 453.81 ± 118.61 nM against AChE and 199.21 ± 50.35 and 409.41 ± 6.86 nM against BChE, respectively.
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http://dx.doi.org/10.1002/jbt.22197DOI Listing
September 2018