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In this study, the synthesis and characterization of newly designed compounds containing pyrazole, acridine, and benzothiazole groups with their biological activity potentials were evaluated. For this purpose, the starting compound of our study, 1-(benzo[d]thiazol-2-yl)-3-(4-chlorophenyl)-1H-pyrazole-4-carbaldehyde (4), was synthesized according to the Vilsmeier-Haack method. Afterward, a series of new pyrazolo-acridine derivatives (7a-l) were obtained as a result of one-pot three-component reaction of compound 1 with 5,5-dimethyl cyclohexane-1,3?dione and various aromatic amines. The structures of the synthesized compounds were characterized using FT-IR, 1H NMR, 13C NMR, Mass spectroscopy techniques, and elemental analysis. Then, the enzyme inhibition effects of these compounds on acetylcholinesterase (AChE) were investigated. According to the in vitro AChE enzyme activity studies, the most effective inhibitions of the compounds 7f (0.76±0.19 µM), 7d (0.82±0.33 µM), and 7e (1.70±1.66 µM) were determined from their low Ki values. On the other hand, in silico molecular docking interactions of the respective compounds with AChE (pdb id: 4EY9) were carried out by using AutoDock Vina software. The molecular docking analyses showed the effective molecular interactions of all compounds (7a-7l) with the AChE enzyme from their low binding energy values. © 2022 Elsevier B.V. 2016-87; Çankiri Karatekin Üniversitesi This research has been supported by Kütahya Dumlupınar University Scientific Research Projects Coordination Office under grant number 2016-87. Also, authors would like to thank Cankırı Karatekin University for providing spectroanalytical facilities and Kütahya Dumlupınar University, Faculty of Arts and Sciences, Department of Physics for FT-IR measurements. This research has been supported by Kütahya Dumlupınar University Scientific Research Projects Coordination Office under grant number 2016-87 . Also, authors would like to thank Cankırı Karatekin University for providing spectroanalytical facilities and Kütahya Dumlupınar University, Faculty of Arts and Sciences, Department of Physics for FT-IR measurements.

In this study a series of pyrazole-3,4-dicarboxamide (3–10) derivatives bearing sulfonamide moiety were synthesized starting from 1-(3-nitrophenyl)-5-phenyl-1H-pyrazole-3,4-dicarboxylic acid (1). The structures of synthesized molecules were characterized by FT-IR, 1H NMR, 13C NMR, and elemental analysis methods. Human carbonic anhydrase isoenzymes (hCA I and hCA II) were purified separately from erythrocyte cells by the Sepharose-4B-L-tyrosine-sulfanilamide affinity column chromatography and inhibitory effects of newly synthesized sulfonamides on esterase activities of these isoenzymes have been studied as in vitro. The Ki values of compounds were found in the range of 0.056–110.400 μM for hCA I and 0.057–533.400 μM for hCA II. Compound 4 has the highest inhibitory effect for hCA I and hCA II while compound 5 showed lowest inhibition. The structure–activity relationships for the inhibition of these isoforms with the pyrazole-sulfonamides reported here were also elucidated. Keywords: Pyrazole, Pyrazole-3,4-dicarboxamide, Synthesis, Reduction, Carbonic anhydrase, Enzyme inhibition

Sulfonamides represent an important class of biologically active compounds. A sulfonamide possessing carbonic anhydrase (CA) inhibitory properties obtained from a pyrazole based sulfonamide, ethyl 1-(3-nitrophenyl)-5-phenyl-3-((5-sulfamoyl-1,3,4-thiadiazol-2-yl)carbamoyl)-1H-pyrazole-4-carboxylate (1), and its metal complexes with the Ni(II) for (2), Cu(II) for (3) and Zn(II) for (4) have been synthesized. The structures of metal complexes (2–4) were established on the basis of their elemental analysis, 1H NMR, IR, UV–Vis and MS spectral data. The inhibition of two human carbonic anhydrase (hCA, EC 4.2.1.1) isoenzymes I and II, with 1 and synthesized complexes (2–4) and acetazolamide (AAZ) as a control compound was investigated in vitro by using the hydratase and esterase assays. The complexes 2, 3 and 4 showed inhibition constant in the range 0.1460–0.3930 µM for hCA-I and 0.0740–0.0980 µM for hCA-II, and they had effective more inhibitory activity on hCA-I and hCA-II than corresponding free ligand 1 and than AAZ. © 2017 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group., This work was supported by Scientific and Technological Research Council of Turkey (TUB€ İTAK) with Grant No. TBAG-104T406.

WOS: 000427338300002, Ractopamine (RAC) is an important beta-agonist. It improves the growth rate and reduces the fat for animals. It is also utilized as nutrient repartitioning agent. Nonetheless, it is not licensed in many countries and RAC is dangerous for human health when it is used illegally. Thus, the development of the sensitive analytical methods for real samples is crucial. Carbon nitride nanotubes (C3N4NTs)/ionic liquid (ILs) nanocomposite was firstly synthesized for RAC detection in this study. n-hexyl-3-methylimidazolium hexafluoro phosphate was used as ionic liquid. The formation of the surfaces was characterized by scanning electron microscope (SEM), electrochemical impedance spectroscopy (EIS), cyclic voltammetry (CV) and x-ray photoelectron spectroscopy (XPS). The linearity range and the detection limit (LOD) for RAC were calculated as 1.0 x 10(-9)-1.0 x 10(-12) M and 1.0 x 10(-13) M, respectively. (C) 2018 Elsevier B.V. All rights reserved., Scientific and Technological Research Council of Turkey (TUBITAK)Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [116Z153]; TUBITAKTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK), This work was supported by The Scientific and Technological Research Council of Turkey (TUBITAK), with project number 116Z153. We would like to thank TUBITAK for the financial support.

In this study several novel 4-substituted-1-(3-nitrophenyl)-5-phenyl-1H-pyrazole-3-carboxylic acid derivatives were synthesized. The structures of these pyrazole-3-carboxylic acid derivatives were characterized by FT-IR, 1H NMR, 13C NMR, and elemental analysis methods. Synthesized molecules were screened to evaluate their antiproliferative activities against Vero (African green monkey kidney), C6 (rat brain tumor), and HeLa (human uterus carcinoma) cells as in vitro. The tests were carried out as dose-dependent assay starting from 100 to 500 µg/cm3. Ethyl 1-(3-nitrophenyl)-5-phenyl-3-(phenylcarbamoyl)-1H-pyrazole-4-carboxylate exhibited the highest performance against HeLa, Vero, and C6 cells among the synthesized derivatives. Also, it showed better antiproliferative activity compared with 5-fluorouracil (5-FU) against Vero cell. Two compounds showed moderate antiproliferative activities against C6 cell line when compared with 5-FU. Also moderate antiproliferative activities against Vero and HeLa cell lines were found. Graphical abstract: (Chemical Equation Presented). © 2015 Springer-Verlag.

2-(2-Amino-3,5-dinitrophenyl)-2-oxoacetic acid (2) was obtained from hydrolysis of 5,7-dinitroisatin (1) in alkaline media. A novel quinoxaline derivative (3) was synthesized from the reaction of the same compound (1) with o-phenylenediamine. Reacting 2 with ethyl 3-oxo-3-phenylpropanoate yields 6,8-dinitro-2-phenylquinoline-3,4-dicarboxylic acid (4). Then, 4 was converted into new quinoline-diacylchloride, quinoline-ester, quinoline-dicarboxamide, pyridazine, and pyrroledione derivatives (5, 6a, 6b, 6c, 6d, 7a, 7b, 7c, 7d, 8, 9, 10a, 10b, 10c, 10d, 11a, 11b, 12) with SOCl2, alcohols, amines, and hydrazines, respectively. The structures of synthesized compounds were clarified by 1H NMR, 13C NMR, IR, mass and elemental analysis methods.

WOS: 000387978400008, PubMed: 27454619, A series of 1-(3-substituted-phenyl)-5-phenyl-N-3,N-4-bis(5-sulfamoyl-1,3,4-thiadiazol-2-yl)-1H-pyrazole-3,4- dicarboxamides (4-15) were synthesized. The structures of these pyrazole-sulfonamides were confirmed by FT-IR, H-1 NMR, C-13 NMR and elemental analysis methods. Human cytosolic carbonic anhydrase (CA, EC 4.2.1.1) isozymes (hCA I and II) were purified from erythrocyte cells by affinity chromatography. The inhibitory effects of newly synthesized derivatives (4-15) were investigated in vitro on esterase activities of these isozymes. The K-i values were determined as 0.119-3.999 mu M for hCA I and 0.084-0.878 mu Mfor hCA II. The results showed that the compound 6 for hCA I and the compound 11 for hCA II had the highest inhibitory effect. Beside that, the compound 8 had the lowest inhibition effect on both isozymes. (C) 2016 Elsevier Inc. All rights reserved., Dumlupinar University Research FundDumlupinar University [2010/14], This work was supported by the Dumlupinar University Research Fund (Project Number: 2010/14). Also the authors are grateful to the Ataturk University Faculty of Sciences Department of Chemistry for providing the usage of spectroanalytic laboratory facilities and Dumlupinar University Faculty of Arts and Sciences Department of Physics for FT-IR measurements.

In this study, some new derivatives were synthesized of 4-benzoyl-1-(3-nitrophenyl)-5-phenyl-1H-pyrazole-3-carboxylic acid (1) and 4-(ethoxycarbonyl)-1-(3-nitrophenyl)-5-phenyl-1H-pyrazole-3-carboxylic acid (2) that they were pyrazole carboxylic acid derivatives. Firstly, 1 and 2 reacted with SOCl2 to transform them into acyl chlorides (3, 4). Then various bis-carboxamide derivatives (58) were obtained from the reaction of 3 and 4 with various diamines and also a β-hydroxy ester (9) derivative was obtained from the reaction of 3 with ethylene glycol. The structures of synthesized compounds were elucidated with using FT-IR, 1H NMR, 13C NMR and elemental analysis methods.

WOS: 000361782400003, Synthesis, characterization, and antiproliferative activity evaluation of a series of novel pyrazole bis-carboxamide derivatives (8-12) have been described. Synthesized molecules have been screened to evaluate their antiproliferative activities against He La (human uterus carcinoma), Vero (green monkey kidney), and C6 (Rat Brain tumor) cells as in vitro. The tests are carried out as dose-dependent assay starting from 100 mu g/mL to 500 mu g/mL. Generally the compounds have been shown to possess weak antiproliferative activity against all cell lines as compared with Cisplatin and 5-Fluorouracil. Only compound 8 shows moderate antiproliferative activity against Hela cancer cells., Scientific and Research Council of TurkeyTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [106T180]; Dumlupinar University Research FundDumlupinar University [52], This study was supported by the Scientific and Research Council of Turkey (Grant No: 106T180) and Dumlupinar University Research Fund (Grant No: 52). The authors would like to thank Department of Chemistry, Faculty of Sciences, and Ataturk University for providing spectroanalytical facilities and Department of Physics, Faculty of Arts and Sciences, Dumlupinar University for FT IR measurements.

A series of pyrazole-3-carboxylic acid and pyrazole-3,4-dicarboxylic acid derivatives were synthesized, the structures were confirmed by their NMR (1H and13C) and FT-IR spectra, and elemental analyses. The antibacterial and antifungal activities of the compounds against five bacterial and five fungal pathogens were screened using modified agar well diffusion assay. Most of the molecules have inhibitory effects on both standard and clinical Candida albicans strains. However, only the molecules 8, 10, 21, and 22 demonstrate some inhibitory effects on Candida parapsilosis, Candida tropicalis, and Candida glabrata strains. The structure-antifungal activity relationships of the compounds on the C. albicans strains were investigated by electron-conformational method. The pharmacophores and antipharmacophores responsible for the inhibition and non-inhibition of the C. albicans strains were obtained by electronic and geometrical characteristics of the reactive fragments of the molecules. These fragments along with the associated parameters can be used in designing the future more potent antifungal agents. It has been shown that both the positions of electronegative atoms like F and O in the pyrazole substituents and the amount of the associated charges on such atoms are crucial in regulating the strength of antifungal activity for the C. albicans strain. © 2014 Elsevier Masson SAS. All rights reserved.

In this study, a series of pyrazole-sulfonamide derivatives were designed and synthesized from 1-(4-aminophenyl)-4-benzoyl-5-phenyl-N-(5-sulfamoyl-1,3,4- thiadiazol-2-yl)-1H-pyrazole-3-carboxamide (1). The newly synthesized sulfonamides were characterized by FT-IR, 1 H NMR, 13 C NMR, and elemental analyses. The compounds were tested for their in vitro antiproliferative activities against HeLa and C6 cell lines. The tests were carried out as dose-dependent assay starting from 5 to 100 µg/mL. All compounds showed especially cell selective effect against rat brain tumor cells (C6). Some of the tested compounds (3) and (7) showed promising broad spectrum antitumor activity comparable to the activities of the commonly used anticancer drugs, 5-fluorouracil and cisplatin. © 2013 Springer Science+Business Media New York., National Council for Scientific Research: TUBI-TAK 106T180 DPT 2003K120510, Acknowledgments This study was financially supported by the grants from the Scientific and Research Council of Turkey (TUBI-TAK 106T180) and the State Planning Organization (DPT 2003K120510), Turkey.

In the current study, a series of pyrazole-sulfonamide derivatives (2-14) were synthesized, characterized, and the inhibition effects of the derivatives on human carbonic anhydrases (hCA I and hCA II) were investigated as in vitro. Structures of these sulfonamides were confirmed by FT-IR, 1H NMR, 13C NMR and LC-MS analysis. 1H NMR and 13C NMR revealed the tautomeric structures. hCA I and hCA II isozymes were purified from human erythrocytes and inhibitory effects of newly synthesized sulfonamides on esterase activities of these isoenzymes have been studied. The Ki values of compounds were 0.062-1.278 µM for hCA I and 0.012-0.379 µM for hCA II. The inhibition effects of 7 for hCA I and 4 for hCA II isozymes were almost in nanomolar concentration range. © 2012 Elsevier Ltd. All rights reserved., California Department of Fish and Game: STE 1127/15-1 National Council for Scientific Research King Fahd University of Petroleum and Minerals 106T180 King Fahd University of Petroleum and Minerals, The authors are very grateful to The Scientific and Research Council of Turkey (TUBITAK) for providing financial support for this project (Grant No. 106T180). The facility of King Fahd University of Petroleum and Minerals (KFUPM) is used, and KFUPM is gratefully acknowledged for the support of this project. The authors are thankful Stefan Walter and Kerstin Ruecker at Chemistry/Biology Branch of Osnabrück University for LC/MS and TGA measurements, respectively. S.O. is also grateful to German Science Foundation (DFG) for the support of summer research stay at Osnabrück University/Germany with Grant number STE 1127/15-1.

Objectives Two new metal complexes, diaquabis(4-benzoyl-1,5-diphenyl-N-(5-sulfamoyl-1,3,4-thiadiazol-2-yl)-1H-pyrazole-3-carboxamide)cobalt(II) dihydrate (2) and diaquabis(ethyl-1-(3-nitrophenyl)-5-phenyl-3-(5-sulfamoyl-1,3,4-thiadiazol-2-ylcarbamoyl)-1H-pyrazole-4-carboxylate)cobalt(II) monohydrate (4), containing sulfonamide have been synthesized by the reaction of Co(II) with 4-benzoyl-1,5-diphenyl-N-(5-sulfamoyl-1,3,4-thiadiazol-2-yl)-1H-pyrazole-3-carboxamide (1) and ethyl-1-(3-nitrophenyl)-5-phenyl-3-(5-sulfamoyl-1,3,4-thiadiazol-2-ylcarbamoyl)-1H-pyrazole-4-carboxylate (3), respectively. Methods The structures of Co(II) complexes 2 and 4 have been characterised by spectroscopic methods and elemental analyses. Human carbonic anhydrase isoenzymes (hCA-I and hCA-II) were purified from erythrocyte cells by affinity chromatography. The inhibitory effects of ligands 3 and 4, acetazolamide as a control compound and the newly synthesized complexes on the activity of hydratase and esterase of these isoenzymes have been studied in vitro. Key findings The concentration of compounds 2 and 4 producing a 50% inhibition of hydratase activity (IC50 values) were 0.473 ± 0.025 and 0.065 ± 0.002 μm for hCA-I and 0.213 ± 0.015 and 0.833 ± 0.021 μm for hCA-II, respectively. The IC50 values of synthesized compounds 2 and 4 for esterase activity were, 0.058 ± 0.006 and 0.297 ± 0.015 μm for hCA-I and 0.110 ± 0.010 and 0.052 ± 0.002 μm for hCA-II, respectively. In relation to esterase activity, the inhibition equilibrium constants (Ki) were determined as 0.039 ± 0.004 and 0.247 ± 0.035 μm on hCA-I and 0.078 ± 0.002 and 0.363 ± 0.015 μm on hCA-II for 2 and 4, respectively. Conclusions The synthesized compounds 2 and 4 had effective inhibitory activity (P < 0.0001) on hCA-I and hCA-II than the corresponding free ligands, 1 and 3, and acetazolamide. Compounds 2 and 4 might be considered as potential inhibitors.

In this study, some novel inhibitors were synthesised from the further stage reactions of 4-benzoyl-1-(4-nitrophenyl)-5-phenyl-1H-pyrazole-3-carbonyl chloride with 5-amino-1,3,4-thiadiazole-2-sulphonamide 1 (inhibitor 1). They were characterised by elemental and spectral (1H NMR, 13C NMR, IR) analyses. Human carbonic anhydrase isoenzymes (hCA-I and hCA-II) were purified from erythrocyte cells by affinity chromatography. The inhibitory effects of inhibitor 1, acetazolamide (2) and the 11 newly synthesised amides (8-18) on the hydratase and esterase activities of these isoenzymes (hCA-I and hCA-II) were studied in vitro. In relation to these activities, the inhibition equilibrium constants (Ki) were determined. The Ki values for the new compounds (8-18) were observed to be well below that of the parent compound inhibitor 1 and were also compared to 2 under the same experimental conditions. The comparison of the newly synthesised amides to inhibitor 1 and to 2 indicated that the new derivatives preferentially inhibited hCA-II and were more potent inhibitors of hCA-II than the parent inhibitor 1 and 2. © 2011 Informa UK, Ltd., 106T180, This research was funded by TUBITAK (The Foundation of Scientific and Technological Research of Turkey, 106T180) (Ankara, Turkey).

WOS: 000286682300002, 1-(3-Aminophenyl)-4-benzoyl-5-phenyl-1H-pyrazole-3-carboxylic acid (1) was synthesized according to the literature.(1) 2-(3-Aminophenyl)-2,6-dihydro-3,4-diphenyl-7H-pyrazolo[3,4-d]pyridazin-7-one (5) was obtained by the cyclocondensation reaction of 1 with hydrazine hydrate. New pyrazole derivatives of compounds 1 and 5 were synthesized by their reaction with beta-diketones, beta-ketoesters, beta-naphthol, phenol and various other reagents. The structures of the synthesized compounds were characterized by H-1-NMR, C-13-NMR, IR and mass spectroscopy, as well as elemental analysis., Scientific and Research Council of Turkey (TUBITAK)Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK); Dumlupinar University, Scientific Research and Project DepartmentDumlupinar University, This study was funded by The Scientific and Research Council of Turkey (TUBITAK) and Dumlupinar University, Scientific Research and Project Department. In addition, the authors would like to thank the Faculty of Science of Ataturk University, Turkey, for spectral analysis.