Publications by authors named "Burak Tuzun"

23 Publications

  • Page 1 of 1

ADME properties, bioactivity and molecular docking studies of 4-amino-chalcone derivatives: new analogues for the treatment of Alzheimer, glaucoma and epileptic diseases.

In Silico Pharmacol 2021 3;9(1):34. Epub 2021 May 3.

Department of Chemistry, Faculty of Arts and Sciences, Tokat Gaziosmanpaşa University, 60250 Tokat, Turkey.

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.
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http://dx.doi.org/10.1007/s40203-021-00094-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093346PMC
May 2021

Evaluation of potential anti-RNA-dependent RNA polymerase (RdRP) drugs against the newly emerged model of COVID-19 RdRP using computational methods.

Biophys Chem 2021 05 20;272:106564. Epub 2021 Feb 20.

Herbal and Traditional Medicines Research Center, Kerman University of Medical Sciences, Kerman, Iran; Department of Clinical Biochemistry, Afzalipour School of Medicine, Kerman University of medical sciences, Kerman, Iran. Electronic address:

Introduction: Despite all the efforts to treat COVID-19, no particular cure has been found for this virus. Since developing antiviral drugs is a time-consuming process, the most effective approach is to evaluate the approved and under investigation drugs using in silico methods. Among the different targets within the virus structure, as a vital component in the life cycle of coronaviruses, RNA-dependent RNA polymerase (RdRP) can be a critical target for antiviral drugs. The impact of the existence of RNA in the enzyme structure on the binding affinity of anti-RdRP drugs has not been investigated so far.

Methods: In this study, the potential anti-RdRP effects of a variety of drugs from two databases (Zinc database and DrugBank) were evaluated using molecular docking. For this purpose, the newly emerged model of COVID-19 (RdRP) post-translocated catalytic complex (PDB ID: 7BZF) that consists of RNA was chosen as the target.

Results: The results indicated that idarubicin (IDR), a member of the anthracycline antibiotic family, and fenoterol (FNT), a known beta-2 adrenergic agonist drug, tightly bind to the target enzyme and could be used as potential anti-RdRP inhibitors of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). These outcomes revealed that due to the ligand-protein interactions, the presence of RNA in this structure could remarkably affect the binding affinity of inhibitor compounds.

Conclusion: In silico approaches, such as molecular docking, could effectively address the problem of finding appropriate treatment for COVID-19. Our results showed that IDR and FNT have a significant affinity to the RdRP of SARS-CoV-2; therefore, these drugs are remarkable inhibitors of coronaviruses.
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http://dx.doi.org/10.1016/j.bpc.2021.106564DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7895701PMC
May 2021

Synthesis and docking calculations of tetrafluoronaphthalene derivatives and their inhibition profiles against some metabolic enzymes.

Arch Pharm (Weinheim) 2021 Jun 5;354(6):e2000409. Epub 2021 Mar 5.

Chemistry Department, Science Faculty, Sivas Cumhuriyet University, Sivas, Turkey.

Syntheses of tetrahydroepoxy, O-allylic, O-prenylic, and O-propargylic tetrafluoronaphthalene derivatives, starting from 1-bromo-2,3,4,5,6-pentafluorobenzene, are reported here for the first time. The O-substituted tetrafluoronaphthalene derivatives were designed and also synthesized via a one-pot nucleophilic substitution reaction in excellent yields, whereas the tetrafluorotetrahydroepoxynaphthalene derivate was synthesized via a reduction reaction in excellent yield. The chemical structures of all the synthesized molecules were characterized by nuclear magnetic resonance, infrared spectroscopy, and high-resolution mass spectrometry techniques. In this study, a series of novel tetrafluoronaphthalene derivatives (2, 2a, 4-6) was tested toward several enzymes including α-glucosidase, acetylcholinesterase (AChE), and human carbonic anhydrase I and II (hCA I/II). The tetrafluoronaphthalene derivatives 2, 2a, and 4-6 showed IC and K values in the range of 0.83-1.27 and 0.71-1.09 nM against hCA I, 1.26-1.85 and 1.45-5.31 nM against hCA II, 39.02-56.01 and 20.53-56.76 nM against AChE, and 15.27-34.12 and 22.58-30.45 nM against α-glucosidase, respectively. Molecular docking calculations were made to determine the biological activity values of the tetrafluoronaphthalene derivatives against the enzymes. After the calculations, ADME/T analysis was performed to examine the effects on human metabolism. Finally, these compounds had antidiabetic and anticholinesterase potentials.
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http://dx.doi.org/10.1002/ardp.202000409DOI Listing
June 2021

Anti-quorum sensing activity in a PA01 of benzimidazolium salts: electronic, spectral and structural investigations as theoretical approach.

J Biomol Struct Dyn 2021 Mar 1:1-12. Epub 2021 Mar 1.

Faculty of Pharmacy, Department of Basic Pharmaceutical Sciences, Suleyman Demirel University, Isparta, Turkey.

Quorum sensing (QS) is a system used in the expression of virulence factors by many pathogenic bacteria, and blockage of the system is seen as a new and effective strategy in combating with resistant bacteria. The inhibition effects of two benzimidazolium salts, namely 1-(2-methylbenzonitrile)-3-benzylbenzimidazolium bromide () and 1-(-methylphthalimide)-3-(4-methylbenzyl)benzimidazolium bromide (), on quorum sensing-related virulence factors such as pyocyanin, elastase, biofilm formation and swarming motility, which is an opportunistic pathogen a PA01, were investigated in this study. The results show that the compound has a significant inhibition on biofilm formation with 94%. Furthermore, the compounds and reduced swarming motility by 64-69% as well as pyocyanin production by 49-64% in a PA01 without preventing bacterial growth in the tested concentrations. HF, B3LYP and M06-2X methods were used with 3-21 g, 6-31 g, sdd basis sets to compare the chemical activity of the compounds. Theoretically, H NMR, C NMR and Infrared spectra of the compounds were calculated in the HF/6-31++g basis set. The biological activities of the relative compounds were theoretically studied against cancer proteins. Crystal structure of the BRCT repeat region from the breast cancer associated protein, ID: 1JNX, crystal structure of liver cancer protein, ID: 3WZE and crystal structure of lung cancer protein, ID: 5ZMA, were compared. In the docking studies, the best result was obtained with compound against the lung cancer cell with a docking score parameter of -5.85.Communicated by Ramaswamy H. Sarma.
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http://dx.doi.org/10.1080/07391102.2021.1890222DOI Listing
March 2021

Synthesis, molecular docking, and biological activities of new cyanopyridine derivatives containing phenylurea.

Arch Pharm (Weinheim) 2021 Apr 10;354(4):e2000334. Epub 2020 Dec 10.

Department of Chemistry, Faculty of Science and Arts, Tokat Gaziosmanpaşa University, Tokat, Turkey.

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 α-glycosidase (α-Gly). The new cyanopyridine derivatives showed K values in the range of 40.73 ± 6.54 to 87.05 ± 16.98 µM against AChE, 29.17 ± 4.88 to 124.03 ± 22.43 µM against BChE, and 3.66 ± 0.93 to 26.33 ± 5.05 µM against α-Gly. These inhibition effects were compared with standard enzyme inhibitors like tacrine (for AChE and BChE) and acarbose (for α-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 α-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.
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http://dx.doi.org/10.1002/ardp.202000334DOI Listing
April 2021

1,2,3-Triazole substituted phthalocyanine metal complexes as potential inhibitors for anticholinesterase and antidiabetic enzymes with molecular docking studies.

J Biomol Struct Dyn 2020 Dec 9:1-11. Epub 2020 Dec 9.

Department of Fundamental Sciences, Faculty of Technology, Sakarya University of Applied Sciences, Sakarya, Turkey.

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 () effectively inhibited AChE, with values in the range of 40.11 ± 5.61 to 78.27 ± 15.42 µM. For α-glycosidase, the most effective values of compounds and were with 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 () and its metal complexes (-). Biological activities of 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.
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http://dx.doi.org/10.1080/07391102.2020.1857842DOI 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

Biological effects and molecular docking studies of Catechin 5-O-gallate: antioxidant, anticholinergics, antiepileptic and antidiabetic potentials.

J Biomol Struct Dyn 2020 Nov 4:1-9. Epub 2020 Nov 4.

Department of Chemistry, Faculty of Arts and Sciences, Bingol University, Turkey.

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 α-glycosidase (α-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 (Cu) reduction capacity by CUPRAC method, Fe-Fe reducing capacity, DPPH free radical clarifying (DPPH·), ABTS radical clarifying (ABTS) were performed separately and during the study, trolox, α-tocopherol BHT and BHA were used as the reference antioxidant compound. Comparisons were applied with the four standard substances. Communicated by Ramaswamy H. Sarma.
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http://dx.doi.org/10.1080/07391102.2020.1840440DOI Listing
November 2020

Design, synthesis, characterization, biological evaluation, and molecular docking studies of novel 1,2-aminopropanthiols substituted derivatives as selective carbonic anhydrase, acetylcholinesterase and α-glycosidase enzymes inhibitors.

J Biomol Struct Dyn 2020 Aug 27:1-13. Epub 2020 Aug 27.

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

In the article, various substituted derivatives of 1,2-aminopropanthiol () have been prepared by a general and efficient method, in one-steps, starting from available thiirane and aromatic amines (aniline, -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, α-glycosidase, and acetylcholinesterase inhibitory effects. These synthesized novel 1,2-aminopropanthiols substituted derivatives () were found to be effective inhibitors for the α-glycosidase, human carbonic anhydrase I and II, and acetylcholinesterase enzymes, with K values in the range of 11.47 ± 0.87-24.09 ± 6.37 µM for α-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 α-glycosidase. Communicated by Ramaswamy H. Sarma.
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http://dx.doi.org/10.1080/07391102.2020.1811772DOI Listing
August 2020

New anti-viral drugs for the treatment of COVID-19 instead of favipiravir.

J Biomol Struct Dyn 2020 Aug 12:1-11. Epub 2020 Aug 12.

Faculty of Medicine, Department of Gastroenterology, Sivas Cumhuriyet University, Sivas, Turkey.

The SARS-CoV-2 virus is a major problem in the world right now. Currently, all the attention of research centers and governments globally are focused on the investigation of vaccination studies and the discovery of small molecules that inhibit the SARS-CoV-2 virus in the treatment of patients. The goal of this study was to locate small molecules to be used against COVID19 instead of favipiravir. Favipiravir analogues were selected as drug candidates from the PubChem web tool. The RNA dependent RNA polymerase (RdRp) protein was selected as the target protein as favipiravir inhibits this protein in the human body. Initially, the inhibition activity of the studied compounds against RdRp of different virus types was investigated. Then, the inhibition properties of selected drug candidates and favipiravir were examined in detail against SARS-CoV-2 RdRp proteins. It was found that 2-oxo-1-pyrazine-3-carboxamide performed better than favipiravir in the results of molecular docking, molecular mechanics Poisson-Boltzmann surface area (MM-PSBA) calculations, and ADME analyses.Communicated by Ramaswamy H. Sarma.
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http://dx.doi.org/10.1080/07391102.2020.1806112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7484583PMC
August 2020

Determination of the inhibition profiles of pyrazolyl-thiazole derivatives against aldose reductase and α-glycosidase and molecular docking studies.

Arch Pharm (Weinheim) 2020 Dec 6;353(12):e2000118. Epub 2020 Aug 6.

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

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 K value of 7.09 ± 0.19 µM, whereas compound 3e showed the lowest inhibition effects, with a K value of 21.89 ± 1.87 µM. Also, all compounds showed efficient inhibition profiles against α-glycosidase, with K values in the range of 0.43 ± 0.06 to 2.30 ± 0.48 µM, whereas the K 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.
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http://dx.doi.org/10.1002/ardp.202000118DOI Listing
December 2020

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

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

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

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

Bioactivity and molecular docking studies of some nickel complexes: New analogues for the treatment of Alzheimer, glaucoma and epileptic diseases.

Bioorg Chem 2020 08 30;101:104066. Epub 2020 Jun 30.

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

The interaction of the coordination compounds with biological molecules resulted in the investigation of the drug potential of these molecules. In this study, enzyme inhibition of DSA (1-3) coordination compounds that were previously investigated for their anticancer and antibacterial properties was investigated. Also, DSA (1-3) had K values of 635.30 + 152.62, 184.01 + 90.05, and 163.03 ± 60.01 µM against human carbonic anhydrase I, 352.23 ± 143.09, 46.2 ± 15.47, and 54.117 ± 18.80 µM against AChE, 310.64 ± 97.35, 35.54 ± 7.01, and 101.51 ± 15.314 µM against BChE, respectively. The biological activity values of these compounds against enzymes whose name are AChE, BChE, and hCAI were compared. Ellman and Verporte methods were used for the study of these enzymes. Cholinesterase inhibitors, also known as anti-cholinesterase and cholinesterase blocking drugs, are chemicals that prevent the breakdown of the neurotransmitter acetylcholine or butyrylcholine. They may be used as drugs for Alzheimer's and myasthenia gravis. It is a common method for comparing biological activity values of nickel complexes with molecular docking calculations. Nickel complexes were studied against enzymes that are human carbonic anhydrase isozyme I for ID 2CAB (hCA I), butyrylcholinesterase for ID 1P0I (BChE), and acetylcholinesterase for ID 1EEA (AChE), respectively.
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http://dx.doi.org/10.1016/j.bioorg.2020.104066DOI Listing
August 2020

Novel propanolamine derivatives attached to 2-metoxifenol moiety: Synthesis, characterization, biological properties, and molecular docking studies.

Bioorg Chem 2020 08 24;101:103969. Epub 2020 May 24.

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

The synthesis of seven new ß-amino alcohols was designed and performed by starting from eugenol, a natural phenolic compound known to be biologically active. The synthesized compounds were obtained in yields ranging from 54 to 81%. Molecule structures were determined with FT-IR, H NMR and C NMR spectroscopies. In addition, the inhibitory effects of these substances on acetylcholinesterase (AChE), α-glycosidase (α-Gly), human carbonic anhydrase I (hCA I), and human carbonic anhydrase II (hCA II) enzymes have been investigated. It has been seen that all compounds have a better ability to inhibit compared to existing tried inhibitors. Among these, the best inhibitor against AChE enzyme is 2b (Ki 62.08 ± 11.67 µM and IC 90.33), and against α-Gly, 2c showed the highest effect (Ki 0.33 ± 0.08 µM and IC 0.28). The best inhibitor against hCA I, and hCA II enzymes is compound 2f. For hCA I and hCA II, Ki value was measured as 9.68 ± 1.32 and 11.46 ± 2.64 µM and IC values as 7.37 and 8.26 µM respectively. The interactions of the studied new propanolamine derivatives with the enzymes were done by molecular docking calculations and their biological activities were compared to the experimental tests. Studied enzymes in molecular docking calculations are acetylcholinesterase (AChE) is PDB ID: 4M0E, α-glycosidase (α-Gly) is PDB ID: 1R47, human carbonic anhydrase isoenzyme I (hCA I) PDB ID: 3LXE is human carbonic anhydrase isoenzyme II (hCA II) is PDB ID: 5 AML.
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http://dx.doi.org/10.1016/j.bioorg.2020.103969DOI 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

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

J Biomol Struct Dyn 2021 Jun 15;39(9):3336-3346. Epub 2020 May 15.

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

This work is devoted to definition of the direction of reaction between 1-benzenesulfonylimino pyridinium chloride and α- or β-halo-containing sulfamides, chloroacetic acid, 1-chloro-2,3-dihydroxypropane, etc. The optimal conditions for the synchronous reaction of heterocyclization are determined. Benzenesulfonyliminopyridinium chloride was obtained to form pyrazolopyridines with 1,2-polarophiles, and pyridazine pyridines with 1,3-polarophiles. These novel derivatives were found as effective inhibitors of the α-glycosidase with K values in the range of 13.66 ± 2.63-60.63 ± 12.71 nM. The molecules () against enzyme were compared theoretically with the help of molecular docking to compare biological activities. The results were compared with the numerical values of the parameters obtained from molecular docking calculations and found to be in great agreement with the experimental results. However, ADME analysis of molecules was performed. Also, the compounds exhibited significant anticancer effect depending on the doses administered.Communicated by Ramaswamy H. Sarma.
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http://dx.doi.org/10.1080/07391102.2020.1763838DOI Listing
June 2021

Synthesis, characterization, biological evaluation, and molecular docking studies of some piperonyl-based 4-thiazolidinone derivatives.

Arch Pharm (Weinheim) 2020 Jan 28;353(1):e1900304. Epub 2019 Nov 28.

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

Heterocyclic compounds are of particular importance among pharmacologically active compounds. In this study, some piperonyl-based 4-thiazolidinone derivatives (2a-i) were synthesized and characterized by spectroscopic assays. All molecules were tested as enzyme inhibitory factors. These compounds were effective inhibitors of the enzymes acetylcholinesterase (AChE), α-glycosidase (α-Gly), and the human carbonic anhydrase I and II isoforms (hCA I and II), with K values in the range of 8.90-66.51 nM for α-Gly, 94.8-289.5 nM for hCA I, 106.3-304.6 nM for hCA II, and 0.55-2.36 nM for AChE. The synthesized molecules were also studied theoretically. Molecular docking calculations were performed to investigate the interaction between the target protein and molecules. CA inhibitor compounds have been clinically used for almost 60 years as antiglaucoma and diuretic drugs. The inhibition of the AChE enzyme results in the blockage of ACh hydrolysis. On the contrary, the design of inhibitor compounds or/and modulators for AChE is of major interest as it is one of the most popular tools to prevent Alzheimer's disease.
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http://dx.doi.org/10.1002/ardp.201900304DOI Listing
January 2020

Investi̇gati̇on of pyrazoly derivatives schi̇ff base li̇gands and thei̇r metal complexes used as anti-cancer drug.

Authors:
Burak Tüzün

Spectrochim Acta A Mol Biomol Spectrosc 2020 Feb 15;227:117663. Epub 2019 Oct 15.

Sivas Cumhuriyet University, Faculty of Science, Chemistry Department, SİVAS, Turkey. Electronic address:

In this study, six pyrazole derivatives containing hetero atoms have been analyzed using theoretical calculation method. The ligands were tested by HF, B3LYP and M06-2X methods using 3-21G, 6-31G, 6-31G(d, p), and sdd basis sets. The results showed that Ligand 5 has a HOMO value of -7.470 at HF / 6-31g (d.p) level. These ligands were investigated in IR, NMR, and UV-VIS spectrum, then experimental values were compared with IR and NMR spectrum data. The solvents, whose effects were investigated in UV-VIS spectrum, were gas phase (ε = 1), toluene (ε = 2.3741), chloroform (ε = 4.7113), methanol (ε = 32.613), water (ε = 78.3553), and n-methylformamide-mixture (ε = 181.56). Metal complexes of tested ligands were produced with copper, nickel, and zinc. Lastly, the interactions between these six pyrazole derivatives and three proteins, namely 3dju, 2IJN, and 1JNX, were also examined. Biological and anti-cancer properties of six pyrazole derivatives were analyzed by DockingServer. In docking calculations, Estimated Free Energy of Binding value of Ligand 5 was found to be -4.87, -4.82, -1.73 respectively, which indicated the highest biological activity.
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http://dx.doi.org/10.1016/j.saa.2019.117663DOI Listing
February 2020

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

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

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

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

Synthesis of non-peripherally tetra-substituted copper(ii) phthalocyanines: characterization, optical and surface properties, fabrication and photo-electrical properties of a photosensitive diode.

Dalton Trans 2019 Oct;48(39):14839-14852

Department of Chemistry, Sakarya University, 54187 Esentepe, Sakarya, Turkey.

This study describes the synthesis and characterization of a non-peripherally tetra-substituted copper(ii) phthalocyanine bearing 4-(trifluoromethoxy)phenol groups. Some spectroscopic techniques such as FT-IR, 1H-NMR, 13C-NMR, MALDI-TOF, SEM and UV-vis were used to characterize the compounds. The novel molecule of 3-(4-(trifluoromethoxy) phenoxy) phthalonitrile (1) was confirmed and its molecular structure and supra-molecular dynamics were revealed by the analysis of single crystal X-ray diffraction measurements. Ligand (1) and its copper(ii) phthalocyanine (2) were theoretically examined via HF and B3LYP, M06-2X methods by using the 3-21G, 6-31G and sdd basis sets. The calculated values of IR, NMR and UV-Vis spectra for ligand (1) and its copper(ii) phthalocyanine (2) were compared with the experimentally obtained values. The absorbance and reflectance spectra, optical band gaps, refractive indices, and the optical and electrical conductivities of compound (2) for different concentrations were investigated in detail. We fabricated a photosensitive diode and investigated its photo-electrical properties under dark and light conditions.
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http://dx.doi.org/10.1039/c9dt02868dDOI Listing
October 2019

Investigations over optical properties of boron complexes of benzothiazolines.

Spectrochim Acta A Mol Biomol Spectrosc 2019 Feb 2;208:48-56. Epub 2018 Oct 2.

Sivas Cumhuriyet University, Science Faculty, Chemistry Department, 58140 Sivas, Turkey. Electronic address:

Quantum chemical analyses over benzothiazolines and their boron complexes are performed. In calculations, M06-2X method was selected with 6-31 + G(d,p) level. Structural and spectral (IR and NMR) characterization of studied compounds are done in detail. Quantum chemical descriptors (QCDs) are calculated to investigate the optical properties. Furthermore, molecular electrostatic potential (MEP) maps of the studied compounds are calculated by using electro-static potential (ESP) charges. According to QCDs and MEP maps, NLO properties of boron complexes are more than those of benzothiazolines and (Z)-2-((pyridin-2-ylmethylene)amino) benzenethiolatebutane-1,3-bis(olate)boron(III), complex (7), has the most NLO activity in studied compounds. Finally, solvent effect on NLO activity are investigated by calculating UV-vis spectrum in gas phase (ε = 1), toluene (ε = 2.3741), chloroform (ε = 4.7113), methanol (ε = 32.613), water (ε = 78.3553) and n-methylformamide-mixture (ε = 181.56). According to these spectra results, NLO activity mainly increases with increasing of polarizability of media.
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http://dx.doi.org/10.1016/j.saa.2018.09.060DOI Listing
February 2019

Anticorrosive Effects of Some Thiophene Derivatives Against the Corrosion of Iron: A Computational Study.

Front Chem 2018 7;6:155. Epub 2018 May 7.

Department of Chemistry, Faculty of Science, Cumhuriyet University, Sivas, Turkey.

It is known that iron is one of the most widely used metals in industrial production. In this work, the inhibition performances of three thiophene derivatives on the corrosion of iron were investigated in the light of several theoretical approaches. In the section including DFT calculations, several global reactivity descriptors such as , , ionization energy (), electron affinity (), HOMO-LUMO energy gap (Δ), chemical hardness (η), softness (σ), as well as local reactivity descriptors like Fukui indices, local softness, and local electrophilicity were considered and discussed. The adsorption behaviors of considered thiophene derivatives on Fe(110) surface were investigated using molecular dynamics simulation approach. To determine the most active corrosion inhibitor among studied thiophene derivatives, we used the principle component analysis (PCA) and agglomerative hierarchical cluster analysis (AHCA). Accordingly, all data obtained using various theoretical calculation techniques are consistent with experiments.
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http://dx.doi.org/10.3389/fchem.2018.00155DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5949371PMC
May 2018

4D-QSAR Study of Some Pyrazole Pyridine Carboxylic Acid Derivatives By Electron Conformational-Genetic Algorithm Method.

Curr Comput Aided Drug Des 2018 ;14(4):370-384

Department of Chemistry, Science Faculty, Erciyes University, Kayseri, Turkey.

Introduction: In the present work, pharmacophore identification and biological activity prediction for 86 pyrazole pyridine carboxylic acid derivatives were made using the electron conformational genetic algorithm approach which was introduced as a 4D-QSAR analysis by us in recent years. In the light of the data obtained from quantum chemical calculations at HF/6-311 G** level, the Electron Conformational Matrices of Congruity (ECMC) were constructed by EMRE software. Comparing the matrices, electron conformational submatrix of activity (ECSA, Pha) was revealed that are common for these compounds within a minimum tolerance. A parameter pool was generated considering the obtained pharmacophore.

Methods: To determine the theoretical biological activity of molecules and identify the best subset of variables affecting bioactivities, we used the nonlinear least square regression method and genetic algorithm.

Results: The results obtained in this study are in good agreement with the experimental data presented in the literature. The model for training and test sets attained by the optimum 12 parameters gave highly satisfactory results with R2 training= 0.889, q2=0.839 and SEtraining=0.066, q2 ext1 = 0.770, q2 ext2 = 0.750, q2 ext3=0.824, ccctr = 0.941, ccctest = 0.869 and cccall = 0.927.
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http://dx.doi.org/10.2174/1573409914666180514094202DOI Listing
January 2019