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In this study, the preparation, aggregation behavior and investigation of carbonic anhydrase and cholinesterase enzyme inhibition features of non-peripherally (4-isopropylbenzyl)oxy-substituted phthalocyanines (

In this study, preparation, as well as investigation of α-glycosidase and cholinesterase (ChE) enzyme inhibition activities of furan-2-ylmethoxy-substituted compounds 1-7, are reported. Peripherally, tetra-substituted copper and manganese phthalocyanines (5 and 6) were synthesized for the first time. The substitution of furan-2-ylmethoxy groups provides remarkable solubility to the complex and redshift of the phthalocyanines Q-band. Besides, the inhibitory effects of these compounds on acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and α-glycosidase (α-Gly) enzymes have been investigated. The AChE was inhibited by these compounds (1-7) in low micromolar levels, and K i values were recorded between 11.17 ± 1.03 and 83.28 ± 11.08 µM. Against the BChE, the compounds demonstrated K i values from 7.55 ± 0.98 to 81.35 ± 12.80 µM. Also, these compounds (1-7) effectively inhibited α-glycosidase, with K i values in the range of 744.87 ± 67.33 to 1094.38 ± 88.91 µM. For α-glycosidase, the most effective K i values of phthalocyanines 3 and 6 were with K i values of 744.87 ± 67.33 and 880.36 ± 56.77 µM, respectively. Moreover, the studied metal complexes were docked with target proteins PDB ID: 4PQE, 1P0I, and 3WY1. Pharmacokinetic parameters and secondary chemical interactions that play an active role in interaction were predicted with docking simulation results. Overall, furan-2-ylmethoxy-substituted phthalocyanines can be considered as potential agents for the treatment of Alzheimer's diseases and diabetes mellitus.

In recent years, acetylcholinesterase (AChE) and α-glycosidase (α-gly) inhibition have emerged as a promising and important approach for pharmacological intervention in many diseases such as glaucoma, epilepsy, obesity, cancer, and Alzheimer's. In this manner, the preparation and enzyme inhibition activities of peripherally 1,2,3-triazole group substituted metallophthalocyanine derivatives with strong absorption in the visible region were presented. These novel metallophthalocyanine derivatives (2-6) effectively inhibited AChE, with Ki values in the range of 40.11 ± 5.61 to 78.27 ± 15.42 µM. For α-glycosidase, the most effective Ki values of compounds 1 and 2 were with Ki values of 16.11 ± 3.13 and 18.31 ± 2.42 µM, respectively. Also, theoretical calculations were investigated to compare the chemical and biological activities of the ligand (1) and its metal complexes (2–6). Biological activities of 1 and its complexes against acetylcholinesterase for ID 4M0E (AChE) and α-glycosidase for ID 1R47 (α-gly) are calculated. Theoretical calculations were compatible with the experimental results and these 1,2,3-triazole substituted phthalocyanine metal complexes were found to be efficient inhibitors for anticholinesterase and antidiabetic enzymes. Communicated by Ramaswamy H. Sarma

In the article, various substituted derivatives of 1,2-aminopropanthiol (1a–g) have been prepared by a general and efficient method, in one-steps, starting from available thiirane and aromatic amines (aniline, o-toluidine) as a convenient source of sulfur and nitrogen. The synthesized compounds were fully characterized by spectral and analytical data. Seven novel compounds are synthesized. The biochemical properties indicating their potential for constituting an anti-Alzheimer’s disease substance were also recorded revealing strong carbonic anhydrase I, and II, ?-glycosidase, and acetylcholinesterase inhibitory effects. These synthesized novel 1,2-aminopropanthiols substituted derivatives (1a–g) were found to be effective inhibitors for the ?-glycosidase, human carbonic anhydrase I and II, and acetylcholinesterase enzymes, with Ki values in the range of 11.47 ± 0.87–24.09 ± 6.37 µM for ?-glycosidase, 29.30 ± 4.67-79.01 ± 4.49 µM for hCA I, 14.27 ± 2.82-30.85 ± 12.24 µM for hCA II and 5.76 ± 1.55–55.39 ± 2.27 µM for AChE, respectively. In the last step of this study, molecular docking calculations were obtained in order to compare the biological activities of indicated molecules against the enzymes of acetylcholinesterase, butyrylcholinesterase and ?-glycosidase. Communicated by Ramaswamy H. Sarma. © 2020 Informa UK Limited, trading as Taylor & Francis Group., RSP-2019/59; -4-BGM-GIN-2017-3(29)-19/05/4-M-07; RGD-020; King Saud University, KSU, This work is supported by the Scientific Research Project Fund of Sivas Cumhuriyet University under the project number RGD-020. This research was made possible by TUBITAK ULAKBIM, High Performance and Grid Computing Center (TR-Grid e-Infrastructure). S. Alwasel would like to extend his sincere appreciation to the Researchers Supporting Project (RSP-2019/59), King Saud University, Saudi Arabia, for support. This work was carried out with the support of the Science Development Fund under the President of Azerbaijan Republic-EIF/GAM-4-BGM-GIN-2017-3(29)-19/05/4-M-07., This research was made possible by TUBITAK ULAKBIM, High Performance and Grid Computing Center (TR-Grid e-Infrastructure). S. Alwasel would like to extend his sincere appreciation to the Researchers Supporting Project (RSP-2019/59), King Saud University, Saudi Arabia, for support. This work was carried out with the support of the Science Development Fund under the President of Azerbaijan Republic-EIF/GAM-4-BGM-GIN-2017-3(29)-19/05/4-M-07.

Gallocatechin gallate is a form of catechin and an ester of gallocatechin and gallic acid. This is an epimer of the gallate epigallocatechin. In this study, the effect of this molecule, containing a biologically active group, was investigated in terms of important metabolic enzymes (carbonic anhydrase isoenzymes I and II (hCA I and II), achethylcholinesterase (AChE) and a-glycosidase (a-Gly) enzymes). The molecular docking method used to compare the biological activities of the Catechin 5-O-gallate molecule against enzymes was used. Afterwards, the ADME/T analysis was performed to investigate the drug availability of the Catechin 5-O-gallate molecule and the parameters obtained from ADME/T analysis were examined. Continuation of this study, for evaluating antioxidant and radical scavenging capacity Catechin 5-O-gallate, cupric ion (Cu2þ) reduction capacity by CUPRAC method, Fe3þ-Fe2þ reducing capacity, DPPH free radical clarifying (DPPH· ), ABTS radical clarifying (ABTS þ) were performed separately and during the study, trolox, a-tocopherol BHT and BHA were used as the reference antioxidant compound. Comparisons were applied with the four standard substances. Abbreviations: ADME: absorption, distribution, metabolism and excretion; ACR: acarbose; AZA: acetazolamide; AChE: achethylcholinesterase; ABTS: 2, 2’-azino-Bis-3-ethylbenzothiazoline-6-sulfonic acid (biochemical reagent); a-Gly: a-glycosidase; BHA: butylated hydroxyanisole; BHT: butylated hydroxytoluene; BChE: butyrylcholinesterase; CA: carbonic anhydrase; CUPRAC: cupric reducing antioxidant capacity; DPPH: 2,2-diphenyl-1-picrylhydrazyl; EGCG: gallate epigallocatechin; GA: gallic acid; GCG: gallocatechin gallate

In this study, in vitro inhibition effects of (E)-1-(4-aminophenyl)-3-(aryl) prop-2-en-1-one (4-amino-chalcones) derivatives (3a–o) on acetylcholinesterase (AChE) enzyme and human erythrocyte carbonic anhydrase I and II isoenzymes (hCA I- II) were investigated. And also, the biological activities of 4-amino-chalcone derivatives against enzymes which names are acetylcholinesterase (PDB ID: 1OCE), human Carbonic Anhydrase I (PDB ID: 2CAB), human carbonic anhydrase II (PDB ID: 3DC3), were compared. After the results obtained, ADME/T analysis was performed in order to use 4-amino-chalcone derivatives as a drug in the future. Effective inhibitors of carbonic anhydrase I and II isozymes (hCAI and II) and acetylcholinesterase (AChE) enzymes with Ki values in the range of 2.55 ± 0.35–11.75 ± 3.57 nM for hCA I, 4.31 ± 0.78–17.55 ± 5.86 nM for hCA II and 96.01 ± 25.34–1411.41 ± 32.88 nM for AChE, respectively, were the 4-amino-chalcone derivatives (3a–o) molecules. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40203-021-00094-x.

A new class of cyanopyridine derivatives (10a-e and 11a-e) containing the phenylurea unit was synthesized and tested against some metabolic enzymes including acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and alpha-glycosidase (alpha-Gly). The new cyanopyridine derivatives showed K-i values in the range of 40.73 +/- 6.54 to 87.05 +/- 16.98 mu M against AChE, 29.17 +/- 4.88 to 124.03 +/- 22.43 mu M against BChE, and 3.66 +/- 0.93 to 26.33 +/- 5.05 mu M against alpha-Gly. These inhibition effects were compared with standard enzyme inhibitors like tacrine (for AChE and BChE) and acarbose (for alpha-Gly). Also, these cyanopyridine derivatives with the best inhibition score were docked into the active site of the indicated metabolic enzymes. Finally, molecular docking calculations were made to compare the biological activities of the compounds against AChE (-8.81 kcal/mol for molecule 11d), BChE (-3.52 kcal/mol for molecule 11d), and alpha-Gly (-2.98 kcal/mol for molecule 11a). After molecular docking calculations, the ADME/T analysis was performed to examine the future drug use properties of the new cyanopyridine derivatives containing phenylurea., This study is supported by the Scientific Research Project Fund of Sivas Cumhuriyet University under project number RGD‐020. This study was made possible by TUBITAK ULAKBIM, High Performance and Grid Computing Center (TR‐Grid e‐Infrastructure).

Okten, Salih/0000-0001-9656-1803; Gulcin, ilhami/0000-0001-5993-1668; aydin, ali/0000-0002-9550-9111; Taslimi, Parham/0000-0002-3171-0633 WOS:000567558100004 PubMed: 32537757 A series of substituted quinolines was screened for their antiproliferative, cytotoxic, antibacterial activities, DNA/protein binding affinity, and anticholinergic properties by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide cell proliferation, lactate dehydrogenase cytotoxicity, and microdilution assays, the Wolfe-Shimmer equality method, the Ellman method, and the esterase assay, respectively. The results of the cytotoxic and anticancer activities of the compounds displayed that 6-bromotetrahydroquinoline (2), 6,8-dibromotetrahydroquinoline (3), 8-bromo-6-cyanoquinoline (10), 5-bromo-6,8-dimethoxyquinoline (12), the novelN-nitrated 6,8-dimethoxyquinoline (13), and 5,7-dibromo-8-hydroxyquinoline (17) showed a significant antiproliferative potency against the A549, HeLa, HT29, Hep3B, and MCF7 cancer cell lines (IC50 = 2-50 mu g/ml) and low cytotoxicity (similar to 7-35%) as the controls, 5-fluorouracil and cisplatin. The compound-DNA linkages are hyperchromic or hypochromic, causing variations in their spectra. This situation shows that they can be bound to DNA with the groove-binding mode, withK(b)value in the range of 2.0 x 10(3)-2.2 x 10(5) M-1. Studies on human Gram(+) and Gram(-) pathogenic bacteria showed that the substituted quinolines exhibited selective antimicrobial activities with MIC values of 62.50-250 mu g/ml. All tested quinoline derivatives were found to be effective inhibitors of acetylcholinesterase (AChE) and the human carbonic anhydrase I and II isoforms (hCA I and II), withK(i)values of 46.04-956.82 nM for hCA I, 54.95-976.93 nM for hCA II, and 5.51-155.22 nM for AChE. As a result, the preliminary data showed that substituted quinolines displayed effective pharmacological features. Molecular docking studies were performed to investigate the binding modes and interaction energies for compounds2-17with AChE (PDB ID: 4EY6), hCA I (PDB ID: 1BMZ), and hCA II (PDB ID: 2ABE).

Demir, Yeliz; Ardahan Üniversitesi - Nihat Delibalta Göle Meslek Yüksekokulu - Eczane Hizmetleri Bölümü - Eczane Hizmetleri Programı - Makale, Aldose reductase (AR) is the first and rate‐limiting enzyme of the polyol pathway, which converts glucose to sorbitol in an NADPH‐dependent reaction. α‐Glycosidase breaks down starch and disaccharides to glucose. Hence, inhibition of these enzymes can be regarded a considerable approach in the treatment of diabetic complications. AR was purified from sheep liver using simple chromatographic methods. The inhibitory effects of pyrazolyl–thiazoles ((3aR,4S,7R,7aS)‐2‐(4‐{1‐[4‐(4‐bromophenyl) thiazol‐2‐yl]‐5‐(aryl)‐4,5‐dihydro‐1H‐pyrazol‐3‐yl}phenyl)‐3a,4,7,7a‐tetrahydro‐1H‐ 4,7‐methanoisoindole‐1,3(2H)‐dione derivatives; 3a–i) on AR and α‐glycosidase enzymes were investigated. All compounds showed a good inhibitory action against AR and α‐glycosidase. Among these compounds, compound 3d exhibited the best inhibition profiles against AR, with a Ki value of 7.09 ± 0.19 μM, whereas compound 3e showed the lowest inhibition effects, with a Ki value of 21.89 ± 1.87 μM. Also, all compounds showed efficient inhibition profiles against α‐glycosidase, with Ki values in the range of 0.43 ± 0.06 to 2.30 ± 0.48 μM, whereas the Ki value of acarbose was 12.60 ± 0.78 μM. Lastly, molecular modeling approaches were implemented to predict the binding affinities of compounds against AR and α‐glycosidase. In addition, the ADME analysis of the molecules was performed.

In this study, first, Schiff base-containing chalcone derivatives were synthesized. The human carbonic anhydrase (hCA) isoenzymes I and II were then purified from human erythrocytes using Sepharose-4B-l-tyrosine-sulfanilamide affinity chromatography. In addition, the inhibitory effects of the newly synthesized compounds on the activities of hCA and acetylcholinesterase (AChE) were investigated in vitro, using the esterase and acetylcholine iodide method. The IC50 values were determined and the Ki values of AChE and hCA activities were calculated from the Lineweaver-Burk graphs determined in this study. The hCA I isoform was inhibited by these chalcone derivatives containing Schiff bases (3a-j and 5a-f) in low nanomolar levels, whose Ki values ranged between 141.88 ± 24.10 and 2,234.47 ± 38.11 nM. Against the physiologically dominant isoform hCA II, the compounds demonstrated Ki values varying from 199.31 ± 40.45 to 602.79 ± 263.22 nM. Also, these compounds effectively inhibited AChE, with Ki values ranging from 20.41 ± 6.04 to 125.94 ± 23.88 nM. According to these results, the newly synthesized molecules were found to be potent inhibitors of these enzymes.

Taslimi, Parham/0000-0002-3171-0633; Okten, Salih/0000-0001-9656-1803 WOS:000573639200003 Regioselective routes are described for convenient preparation of novel piperazine/morpholine substituted quinoline derivatives at C-3, C-6 and C-8 starting with 3,6,8-tribromoquinoline (6) by nucleophilic substitution via conventional heating or microwave assisted reaction conditions. 3,6,8-Tribromoquinoline (6) was treated with piperazine and morpholine under microvawe irradiation, which selectively furnished 3-mopholinyl and 3-piperazinyl quinoline derivatives 7 and 8 in yields of 58% and 60%, respectively. On the other hand, the activation of benzene cycle of quinoline by nitration of 3,6,8-tribromoquinoline, giving 5-nitro-3,6,8-tribromoquinoline (18) in quantitative yield, was enabled. Then, the bromines at C-6 and C-8 were selectively exchanged by morpholine and piperazine via SNAr reactions. Thus, 6,8-dimopholinylquinoline (22) and 5-nitro-6,8-dipiperazinylquinoline (24), biologically valuable derivatives, were prepared in high yields (82% and 72%, respectively). The synthesized compounds were fully characterizated by H-1 NMR, C-13 NMR, 2D NMR, XRD, HRMS and IR spectra. The novel molecules had effective inhibition profiles against some metabolic enzymes. Also, they have the potential of drug candidates to treat of some diseases including glaucoma, epilepsy, Alzheimer's disease (AD), leukemia, and type-2 diabetes mellitus (T2DM). (C) 2020 Elsevier B.V. All rights reserved. Scientific and Technological Research Council of Turkey (TUBITAK)Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [112T394] This study was financially supported by grants from the Scientific and Technological Research Council of Turkey (TUBITAK, Project number: 112T394). The authors thank to Scientific and Technological Research Application and Research Center, Sinop University, Turkey, for the use of the Bruker D8-QUEST diffractometer.

WOS: 000462504500015, A series of novel 1,3,5-trisubstituted pyrazoline derivatives, (3aR,4S,7R,7aS)-2-[4-[1-acetyl-5-(aryl/heteroaryl)-4,5-dihydro-1H-pyrazol-3-yl]phenyl]-3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindole-1,3(2H)-diones, were synthesized and evaluated for their antimicrobial and anticancer activities. In addition, the compounds were tested against acetylcholinesterase (AChE) enzyme and two physiologically relevant carbonic anhydrase I and II isozymes (hCA I and II). In this study, inhibition of hCA I and hCA II by the novel synthesized 1,3,5-trisubstituted pyrazolines was impressive, with K-i values in the range of 3.33-7.90nM for hCA I and 2.07-8.47nM for hCA II, while the K-i values of these compounds for AChE were recorded in the range of 9.61-48.42nM, respectively. Two compounds can be investigated as the leader compounds because of their lowest K-i values to make further detailed CA inhibition studies. [GRAPHICS] ., Scientific and Technological Research Council of Turkey (TUBITAK) [111T990], The authors are indebted to The Scientific and Technological Research Council of Turkey (TUBITAK Project No: 111T990) for financial supports.

WOS: 000457586700007, PubMed ID: 30600535, The synthesis, characterization, aggregation behavior, theoretical studies, and investigation of antimicrobial, antidiabetic, and anticholinergic properties of 4-(2-(5-amino-4-(4-bromophenyl)-3-methyl-1H-pyrazol-1-yl)ethoxy)phthalonitrile (2) and its soluble aminopyrazole-substituted peripheral metallo (Mn, Co, and Ni)-phthalocyanine complexes (3-5) are reported for the first time. The synthesized compounds and phthalocyanine complexes were characterized spectroscopically. The new phthalonitrile derivative (2) and its peripheral metallophthalocyanine complexes (3-5) were found to be effective inhibitors of alpha-glycosidase, acetylcholinesterase (AChE), human carbonic anhydrase I and II isoforms (hCA I and II), and butyrylcholinesterase (BChE) with K-i values in the range of 1.55 +/- 0.47 to 10.85 +/- 3.43 nM for alpha-glycosidase, 8.44 +/- 0.32 to 21.31 +/- 7.91 nM for hCA I, 11.73 +/- 2.82 to 31.03 +/- 4.81 nM for hCA II, 101.62 +/- 26.58 to 326.54 +/- 89.67 nM for AChE, and 68.68 +/- 11.15 to 109.53 +/- 19.55 nM for BChE. This is the first study of peripherally substituted phthalocyanines containing an aminopyrazole group as potential carbonic anhydrase enzyme inhibitor. Also, the antimicrobial activities of the synthesized compounds were evaluated against six microorganisms (four bacteria and two Candida species) using the broth microdilution method. The gram-positive bacteria were detected to be more sensitive than gram-negative bacteria and yeasts in the synthesized compounds., Sakarya University [2012-02-04-036], Sakarya University, Grant number: 2012-02-04-036

WOS: 000468028500017, PubMed ID: 30597695, A series of 1,3-bis-chalcone derivatives (3a-i, 6a-i and 8) were synthesized and evaluated antimicrobial, antibiofilm and carbonic anhydrase inhibition activities. In this evaluation, 6f was found to be the most active compound showing the same effect as the positive control against Bacillus subtilis and Streptococcus pyogenes in terms of antimicrobial activity. Biofilm structures formed by microorganisms were damaged by compounds at the minimum inhibitory concentration value between 0.5% and 97%.1,3-bis-chalcones ( 3a-i, 6a-i and 8) showed good inhibitory action against human (h) carbonic anhydrase (CA) isoforms I and II. hCA I and II were effectively inhibited by these compounds, with K-i values in the range of 94.33 +/- 13.26 to 787.38 +/- 82.64nM for hCA I, and of 100.37 +/- 11.41 to 801.76 +/- 91.11nM for hCA II, respectively. In contrast, acetazolamide clinically used as CA inhibitor showed K-i value of 1054.38 +/- 207.33nM against hCA I, and 983.78 +/- 251.08nM against hCA II, respectively., Cumhuriyet Universitesi [SBF-035]; Cumhuriyet University, Cumhuriyet Universitesi, Grant/Award Number: SBF-035; Cumhuriyet University

WOS: 000456314600017, The Achillea genus belongs to the Asteraceae family, which is mostly found in the northern hemisphere and is comprised of 115 species in the world. In Turkish flora, there are 52 species and 58 taxa, among them half of which are recorded as endemic. To the best of our knowledge, there has been no biological activity studied in this species until now, with the exception of one study of the antimicrobial activity of certain essential oils. This study focused primarily on the determination of antioxidant, antimicrobial, and enzyme-inhibition activity of aqueous ethanol extract of Turkish endemic Achillea cucullata by in vitro methods. The extract exhibited DPPH radical scavenging activity with an IC50 value of 132.55 +/- 0.026 mu g/mL, the total phenol content was 53.807 +/- 0.059 (mg GAE/g), and the total flavonoid content was 21.372 +/- 0.026 (mg QE/g), on the dry-weight basis. Antimicrobial activity was evaluated by a micro-dilution method focused on five microorganisms; two Gram-positive [Staphylococcus aureus (ATCC 29213) and Enterococcus faecalis (ATCC 29212)], two Gram-negative [Pseudomonas aeruginosa (ATCC 27853) and Escherichia coli (ATCC 25922)], and one fungal strain [Candida albicans (ATCC 10231)]. Results show that the MIC value for the tested microorganism was higher than 5 mg/mL. In this work, acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and alpha-glucosidase enzymes were strongly inhibited by the A. cucullata extract, and the IC50 values for these enzymes were 2.4 mu g/mL, 0.26 mu g/mL, and 24.75 mu g/mL, respectively. Certain acetylcholinesterase inhibitors have been used for treatment of Alzheimer's disease in the past. alpha-Glucosidase inhibitors are strong drug candidates, as well as potential functional food agents, for deferring the postprandial absorbency of glucose. (c) 2018 SAAB. Published by Elsevier B.V. All rights reserved.

WOS: 000455510900008, PubMed ID: 30368973, The 1,2,4-triazole and its derivatives were reported to exhibit various pharmacological activities such as antimicrobial, analgesic, anti-inflammatory, antitumoural, cytotoxic, and antioxidant properties. In this study, a series of triazole compounds (M1-M10) were evaluated for some biological activities. In vitro qualifications of these compounds on acetylcholinesterase (AChE) and human carbonic anhydrase enzyme activities were performed. Also, their antitumoral activities in human colon cancer (HT29) cell line cultures were examined. In addition, colon cancer experimentation was induced in rats by an in vivo method, and the in vivo anticancer effects of triazole derivatives were investigated. Also, the effects of these derivatives in levels of antioxidant vitamin A, vitamin E, and MDA were studied in rat liver and blood samples. Most of the compounds were found to exhibit significant antioxidant and antitumoral activities. All the compounds had cytotoxic activities on HT29 cell lines with their IC50 values lower than 10 mu M concentrations. The low IC50 values of the compounds are M1 (3.88 mu M), M2 (2.18 mu M), M3 (4.2 mu M), M4 (2.58 mu M), M5 (2.88 mu M), M6 (2.37 mu M), M7 (3.49 mu M), M8 (4.01 mu M), M9 (8.90 mu M), and M10 (3.12 mu M).

In this work, the carbonic anhydrase (CA) enzyme was purified from Kangal Akkaraman sheep in Sivas, Turkey with specific activity value of 6681.57 EU/mg and yield of 14.90% with using affinity column chromatography. For designating the subunit molecular mass and enzyme purity, sodium dodecyl sulfate polyacrylamide gel electrophoresis method was used and single band for this procedure was obtained. The molecular mass of CA enzyme was found as 28.89 kDa. In this study, the optimum temperature and optimum pH were obtained from 30 and 7.5. V

WOS: 000427566900001, PubMed ID: 29341350, The purpose of our study is to assist in understanding the effects of wireless electromagnetic waves on carbonic anhydrase (CA) and acetylcholinesterase (AChE) enzymes activities in the different tissues of the rats. For this purpose, two different groups each of which contains eight rats (n=8) were formed as being control group and wireless electromagnetic wave-administered group. The rats were necropsied after 60min from the injection of chemicals into the rats intraperitoneally. The different tissues of the rats were extracted. CA and AChE enzymes activities were measured for each tissue. All the experimental results were provided in mean +/- S.D. Statistical significance was identified to be P

WOS: 000425063500008, PubMed ID: 28792233, The new 1-(4-(3-(aryl)acryloyl)phenyl)-1H-pyrrole-2,5-diones (5a-g) were prepared from 4-aminchalcones (3a-g) and screened for biological activities. All compounds (3a-g and 5a-g), except 3d and 3e displayed good cytotoxic activities with IC50 values in the range of 7.06-67.46 mu M. IC50 value of 5-fluorouracil (5-FU) was 90.36 mu M. Moreover, most of compounds 5a-g showed high antibacterial activity with 8-20 mm of inhibition zone (19-25mm of Sulbactam-Cefoperazone (SCF)). In addition, they showed good inhibitory action against acetylcholinesterase (AChE), and human carbonic anhydrase I, and II (hCA I and hCA II) isoforms. Also, these compounds demonstrated effective inhibition profiles with Ki values of 426.47-699.58 nM against hCA I, 214.92-532.21 nM against hCA II, and 70.470-229.42nM against AChE. On the other hand, acetazolamide, clinically used drug, showed a Ki value of 977.77 +/- 227.4nM against CA I, and 904.47 +/- 106.3 nM against CA II, respectively. Also, tacrine inhibited AChE showed a Ki value of 446.56 +/- 58.33 nM., Scientific and Technological Research Council of Turkey [TUBITAK Project] [111T990], The authors are indebted to the Scientific and Technological Research Council of Turkey [TUBITAK Project No. 111T990] for financial supports.

WOS: 000419943200002, PubMed ID: 28960668, In this study, carbonic anhydrase (CA) enzyme was purified and characterized from blood samples of Kangal Akkaraman sheep and inhibitory properties on certain antibiotics were examined. CA purification was composed of preparation of the hemolysate and conducting the Sepharose-4B-tyrosine-sulfanilamide affinity gel chromatography in having specific activity of 11626EUmg(-1), yield of 14.40%, and 242.76-fold purification. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis was performed to assess the enzyme purity and a single band was observed. Some antibiotics were exhibited in vitro inhibition on the CA activity. IC50 values of these inhibitors were calculated by plotting activity percentage. IC50 values of certain drugs (dexamethasone; caffeine; metamizole sodium; tetramisol; ceftiofur HCl; ivermectin; tavilin 50; penokain G; neosym; and sulfamezathine) were found as 0.38, 8.24, 285.53, 114.77, 5.33, 2.76, 27.58, 213.50, 208.28, and 36.60M, respectively. K-i values of different drugs on Kangal Akkaraman sheep blood CA activity were found in the range of 0.21 +/- 0.038-266.64 +/- 37.11 mu M., Cumhuriyet University Research Fund (CUBAP) [SHMYO-011], We acknowledge with great pleasure the partly support provided by Cumhuriyet University Research Fund (CUBAP), project no: SHMYO-011.

WOS: 000443379600007, PubMed ID: 30079554, We report the synthesis of bromoindenoquinolines (15a-f) by Friedlander reactions in low yields (13-50%) and the conversion of the corresponding phenyl-substituted indenoquinoline derivatives 16-21 in high yields (80-96%) by Suzuki coupling reactions. To explore the structure-activity relationship (SAR), their inhibition potentials to inhibit acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and human carbonic anhydrase cyctosolic (hCA I and II) enzymes were determined. Monophenyl (16-18) indenoquinolines significantly inhibited the AChE and BChE enzymes in ranges of IC50 37-57nM and 84-93nM, respectively, compared with their starting materials 15a-c and reference compounds (galanthamine and tacrine). On the other hand, these novel arylated indenoquinoline-based derivatives were effective inhibitors of the BChE, hCA I and II, BChE and AChE enzymes with K-i values in the range of 37 +/- 2.04 to 88640 +/- 1990nM for AChE, 120.94 +/- 37.06 to 1150.95 +/- 304.48nM for hCA I, 267.58 +/- 98.05 to 1568.16 +/- 438.67nM for hCA II, and 84 +/- 3.86 to 144120 +/- 2910nM for BChE. As a result, monophenyl indenoquinolines 16-18 may have promising anti-Alzheimer drug potential and 3,8-dibromoindenoquinoline amine (15f) can be novel hCA I and hCA II enzyme inhibitors.

WOS: 000419943200008, PubMed ID: 29131470, Some novel derivatives of thiosemicarbazide and 1,2,4-triazole-3-thiol were synthesized and evaluated for their biological activities. The title compounds were prepared starting from readily available pyridine-2,5-dicarboxylic acid. The reaction carboxylic acid with absolute ethanol afforded the corresponding dimethyl pyridine-2,5-dicarboxylate (1). The reaction of dimethyl-2,5-pyridinedicarboxylate (1) with hydrazine hydrate good yielded pyridine-2,5-dicarbohydrazide (2). Refluxing compound 2 with alkyl/aryl isothiocyanate derivatives for 3-8 h afforded 1,4-disubstituted thiosemicarbazides (3a-e). Base-catalyzed intra-molecular dehydrative cyclization of these intermediates furnished the 4,5-disubstituted bis-mercaptotriazoles (4a-e) in good yield (85%-95%). Among the target compounds, 2,2'-(pyridine-2,5-diyldicarbonyl)bis[N-(p-methoxyphenyl)hydrazinecarbothioamide] (3c) showed very high activity with value of 72.93% against 1,1-diphenyl-2-picrylhydrazyl free radical at the concentration of 25 mu g/mL. The inhibitory effects of the target compounds against acetylcholinesterase (AChE), hCA I, and II were studied. AChE, cytosolic hCA I and II isoforms were potently inhibited by synthesized these derivatives with K(i)s in the range of 3.07 +/- 0.76-87.26 +/- 29.25 nM against AChE, in the range of 1.47 +/- 0.37-10.06 +/- 2.96 nM against hCA I, and in the range of 3.55 +/- 0.57-7.66 +/- 2.06 nM against hCA II, respectively., Bingol University Scientific Research Projects Coordination Unit (BUBAP) [2010-013, BAP136-104-2011], We acknowledge with great pleasure the financial support provided by Bingol University Scientific Research Projects Coordination Unit (BUBAP), project no: 2010-013 and BAP136-104-2011.

WOS: 000408915800013, Carbonic anhydrase (CA; EC 4.2.1.1) is used for remedial purposes for several years, as there is significant focus on expanding more new activators (CAAs) and high affinity inhibitors. Alzheimers disease and other similar ailments such as dementia and vascular dementia with Lewy bodies reduce cholinergic activity in the important areas involved in cognition and memory. Prevalent drugs for the symptomatic therapy of dementia are significant in increasing the associated cholinergic deficiency by inhibiting acetylcholinesterase (AChE). These six-membered carbocycles showed nice inhibitory action against AChE and human carbonic anhydrase (hCA) II and I isoforms. The hCA I, II, and AChE were efficiently inhibited by these molecules, with K-i values in the range of 6.70-35.85nM for hCA I, 18.77-60.84nM for hCA II, and 0.74-4.60 for AChE, respectively.

In the present study, human carbonic anhydrase (hCA) enzyme was purified and characterized from fresh blood human red cells by Sepharose-4B-l-tyrosine-sulfanilamide affinity gel chromatography. Secondly, a series of new tetrabromo chalcone derivatives containing 4,7-methanoisoindol-1,3-dione (2a-i) were synthesized from the addition of Br

Glucose-6-phosphate dehydrogenase (G6PD) is the first enzyme on which the pentose phosphate pathway was checked. In this study, purification of a G6PD enzyme was carried out by using rat erythrocytes with a specific activity of 13.7 EU/mg and a yield of 67.7 and 155.6-fold by using 2',5'-ADP Sepharose-4B affinity column chromatography. For the purpose of identifying the purity of enzyme and molecular mass of the subunit, a sodium dodecyl sulfate-polyacrylamide gel electrophoresis was carried out. The molecular mass of subunit was calculated 56.5 kDa approximately. Then, an investigation was carried out regarding the inhibitory effects caused by various metal ions (Fe

WOS: 000401253900001, PubMed ID: 27780313, Benzothiazepine compounds have a wide range of applications such as antibacterial, antidepressants, anticonvulsants, antihypertensives, antibiotics, antifungal, hypnotic, enzyme inhibitors, antitumor, anticancer and anti-HIV agents. In this study, the synthesis of novel tetralone-based benzothiazepine derivatives (1-16) and their in vitro antibacterial activity and human carbonic anhydrase isoenzymes I and II ( hCA I and II) inhibitory effects were investigated. Both isoenzymes were purified by sepharose-4B-L-tyrosine-sulfanilamide affinity chromatography from fresh human red blood cells. All compounds demonstrated the low nanomolar inhibitory effects on both isoenzymes using esterase activity. Benzothiazepine derivative 2 demonstrated the best hCA I inhibitory effect with Ki value of 18.19 nM. Also, benzothiazepine derivative 7 showed the best hCA II inhibitory effect with Ki value of 11.31 nM. On the other hand, acetazolamide clinically used as CA inhibitor, showed Ki value of 19.92 nM against hCA I and 33.60 nM against hCA II, respectively., Gaziosmanpasa University, Scientific Research Projects Commission [BAP2014/33]; King Saud University, Contract Grant Sponsor: Gaziosmanpasa University, Scientific Research Projects Commission.; Contract Grant Number: BAP2014/33.; Contract Grant Sponsor: King Saud University.

WOS: 000418065300004, Novel 4,5-dihydropyrazole derivatives (3a-i), 3-(4-((3aR,4S,7R,7aS)-1,3-dioxo-3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindol-2(3H)-yl)phenyl)-5-phenyl-4,5-dihydro-1H-pyrazole-1-carbothio amide, were obtained by the addition of thiosemicarbazide (2) to the chalcones (1a-i). The addition-cyclization of 2,4-dibromoacetophenone (4) to pyrazole derivatives (3a-i) gave the new pyrazolyl-thiazole derivatives (5a-i), (3aR,4S,7R,7aS)-2-(4-(1-(4-(4-bromophenyl)thiazol-2-yl)-5-phenyl-4,5-dihydro-1H-pyrazol-3-yl)phenyl)-3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindole-1,3(2H)-dione. Antibacterial and acetylcholinesterase (AChE) enzyme and human carbonic anhydrase (hCA) I, and II isoform inhibitory activities of the compounds 3a-i and 5a-i were investigated. Some of the compounds showed promising antibacterial activity. In addition, the hCA II and I were effectively inhibited by the lately synthesized derivatives, with K-i values in the range of 18.90 +/- 2.37 -58.25 +/- 13.62nM for hCA II and 5.72 +/- 0.98 -37.67 +/- 5.54nM for hCA I. Also, the K-i parameters of these compounds for AChE were obtained in the range of 25.47 +/- 11.11-255.74 +/- 82.20nM. Also, acetazolamide, clinical molecule, was used as a CA standard inhibitor that showed K-i value of 70.55 +/- 12.30nM against hCA II, and 67.17 +/- 9.1nM against hCA I, and tacrine inhibited AChE showed K-i value of 263.67 +/- 91.95. [GRAPHICS] ., Scientific and Technological Research Council of Turkey (TUBITAK) [111T990], The authors are indebted to The Scientific and Technological Research Council of Turkey (TUBITAK Project No: 111T990) for financial supports.

WOS: 000397808700014, PubMed ID: 28043719, In the present study, a series of new hybrid compounds containing chalcone and methanoisoindole units 7a-n ((3aR,4S,7R,7aS)-2-(4-((E)-3-(3-aryl) acryloyl) phenyl)-3a, 4,7,7a-tetrahydro-1H-4,7-methanoisoin dole-1,3(2H)-dione) were synthesized, characterized and investigated for their anticancer activity against C6 gliocarcinoma cell in rats, and antimicrobial activity against some human pathogen microorganisms. The compounds 7e, 7h, 7j, 7k, 7L and 7n showed very high anticancer activity with the inhibition range of 80.51-97.02% compared to 5-FU. Some of the compounds exhibited anti-microbial activity. Also, they evaluated for inhibition effects against human carbonic anhydrase I, and II isoenzymes (hCA I and II) with Ki values in the range of 405.26-635.68 pM for hCA I, and 245.40-489.60 pM for hCA II, respectively. These results demonstrated that 3aR, 4S, 7R, 7aS)-2-(4-((E)-3-(3-aryl) acryloyl) phenyl)-3a, 4,7,7a-tetrahy dro-1H-4,7-methanoisoindole-1,3(2H)-dione derivatives could be used in different biomedical applications. (C) 2016 Elsevier Inc. All rights reserved.

Carbonic anhydrase (CA, EC 4.2.1.1) is a member of the metalloenzyme family. It catalyzes the rapid conversion of carbon dioxide (CO

In this work, the carbonic anhydrase (CA) enzyme was purified from Kangal Akkaraman sheep in Sivas, Turkey with specific activity value of 6681.57 EU/mg and yield of 14.90% with using affinity column chromatography. For designating the subunit molecular mass and enzyme purity, sodium dodecyl sulfate polyacrylamide gel electrophoresis method was used and single band for this procedure was obtained. The molecular mass of CA enzyme was found as 28.89 kDa. In this study, the optimum temperature and optimum pH were obtained from 30 and 7.5. Vmax and Km values for p-nitrophenylacetate substrate of the CA were determined from Lineweaver-Burk graphs. Additionally, the inhibitory results of diverse heavy metal ions (Hg+ , Fe2+ , Pb2+ , Co2+ , Ag+ , and Cu2+ ) on sheep were studied. Indeed, CA enzyme activities of Kangal sheep were investigated with using esterase procedure under in vitro conditions. The heavy metal concentrations inhibiting 50% of enzyme activity (IC50 ) and Ki values were obtained.

Taxifolin is a kind of flavanonol, whose biological ability. The objectives of this study were to investigate the antioxidants and antiradical activities of taxifolin by using different in vitro bioanalytical antioxidant methods including DMPD center dot+, ABTS(center dot+), O-2(center dot-) , and DPPH center dot-scavenging effects, the total antioxidant influence, reducing capabilities, and Fe2+-chelating activities. Taxifolin demonstrated 81.02% inhibition of linoleic acid emulsion peroxidation at 30 mu g/mL concentration. At the same concentration, standard antioxidants including trolox, alpha-tocopherol, BHT, and BHA exhibited inhibitions of linoleic acid emulsion as 88.57, 73.88, 94.29, and 90.12%, respectively. Also, taxifolin exhibited effective DMPD center dot+, ABTS(center dot+), O-2(center dot-), and DPPH center dot-scavenging effects, reducing capabilities, and Fe2+-chelating effects. The results obtained from this study clearly showed that taxifolin had marked antioxidant, reducing ability, radical scavenging and metal-chelating activities. Also, this study exhibits a scientific shore for the significant antioxidant activity of taxifolin and its structure-activity insight., Research Chairs Program at King Saud University, The authors declare no conflict of interest. S. H. Alwasel would like to extend his sincere appreciation to the Research Chairs Program at King Saud University for funding this research.

The use of quail meat and eggs has made this animal important in recent years, with its low cost and high yields. Glutathione S-transferases (GST, E.C.2.5.1.18) are an important enzyme family, which play a critical role in detoxification system. In our study, GST was purified from quail liver tissue with 47.88-fold purification and 12.33% recovery by glutathione agarose affinity chromatography. The purity of enzyme was checked by SDS-PAGE method and showed a single band. In addition, inhibition effects of (3aR,4S,7R,7aS)-2-(4-((E)-3-(aryl)acryloyl)phenyl)-3a,4,7,7a-tetrahydro-1H-4,7methanoisoindole-1,3(2H)-dion derivatives (1a-g) were investigated on the enzyme activity. The inhibition parameters (IC50 and Ki values) were calculated for these compounds. IC50 values of these derivatives (1a-e) were found as 23.00, 15.75, 115.50, 10.00, and 28.75 μM, respectively. Ki values of these derivatives (1a-e) were calculated in the range of 3.04 ± 0.50 to 131.50 ± 32.50 μM. However, for f and g compounds, the inhibition effects on the enzyme were not found.

In the present study, human carbonic anhydrase (hCA) enzyme was purified and characterized from fresh blood human red cells by Sepharose-4B-l-tyrosine-sulfanilamide affinity gel chromatography. Secondly, a series of new tetrabromo chalcone derivatives containing 4,7-methanoisoindol-1,3-dione (2a–i) were synthesized from the addition of Br2 to related chalcone derivatives (1a–i). The structures of the new molecules (2a–i) were confirmed by means of 1H NMR, 13C NMR and elemental analysis. Finally, the inhibitory effects of 2a–i on CA activities were investigated using the esterase method under in vitro conditions. The compounds 2a–i exhibited excellent inhibitory effects, in the low nanomolar range, with Ki values in the range of 11.30–21.22 nM against hCA I and in the range of 8.21–12.86 nM against hCA II. Our findings suggest that the new compounds 2a–i have superior inhibitory effect over acetazolamide (AZA), which is used as clinical CA inhibitor, with obtained Ki values of 34.50 and 28.93 nM against the hCA I and II isozymes, respectively. In addition to the inhibition assays, molecular modeling approaches were implemented for prediction of the binding affinities of compounds 2a and 2c, which had the highest inhibition effects, against the hCA I and II isozymes.

Glucose-6-phosphate dehydrogenase (G6PD) is the first enzyme on which the pentose phosphate pathway was checked. In this study, purification of a G6PD enzyme was carried out by using rat erythrocytes with a specific activity of 13.7 EU/mg and a yield of 67.7 and 155.6-fold by using 2′,5′-ADP Sepharose-4B affinity column chromatography. For the purpose of identifying the purity of enzyme and molecular mass of the subunit, a sodium dodecyl sulfate-polyacrylamide gel electrophoresis was carried out. The molecular mass of subunit was calculated 56.5 kDa approximately. Then, an investigation was carried out regarding the inhibitory effects caused by various metal ions (Fe2+, Pb2+, Cd2+, Ag+, and Zn2+) on G6PD enzyme activities, as per Beutler method at 340 nm under in vitro conditions. Lineweaver–Burk diagrams were used for estimation of the IC50 and Ki values for the metals. Ki values for Pb+2, Cd+2, Ag+, and Zn+2 were 113.3, 215.2, 19.4, and 474.7 μM, respectively.

WOS: 000387768300031, beta-Lactams are pharmacologically important compounds because of their various biological uses, including antibiotic and so on. beta-Lactams were synthesized from benzylidene-inden derivatives and acetoxyacetyl chloride. The inhibitory effect of these compounds was examined for human carbonic anhydrase I and II (hCA I, and II) and acetylcholinesterase (AChE). The results reveal that beta-lactams are inhibitors of hCA I, II and AChE. The Ki values of beta-lactams (2a-k) were 0.44-6.29 nM against hCA I, 0.93-8.34 nM against hCA II, and 0.25-1.13 nM against AChE. Our findings indicate that beta-lactams (2a-k) inhibit both carbonic anhydrases (CA) isoenzymes and AChE at low nanomolar concentrations., Sakarya University [BAPK-2012-02-04-031], We gratefully acknowledge the partial financial support for this research project from Sakarya University BAPK-2012-02-04-031.