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Mannich bases (2a–d) of aromatic amines were synthesized by using a conventional microwave technique under solvent-free conditions and characterized by IR and NMR (1H and 13C) and elemental analysis. The inhibitory effects of the synthesized Mannich bases were examined in vitro by using hydratase and esterase assays on carbonic anhydrase I and II isozymes (hCA, EC 4.2.1.1) purified from human erythrocyte cells. Acetazolamide was used as the control compound. The values of IC50, the half-maximum inhibitory concentration, were found for hydratase and esterase activities. Only two compounds (2b and 2d) exhibited poor hCA I and hCA II inhibition effects on esterase activity. In contrast, compounds 2a and 2c could be used as carbonic anhydrase activators as a result of the increased esterase activity of hCA I and hCA II isozymes. © 2021, Macedonian Journal of Chemistry and Chemical Engineering. All Rights Reserved.

INTRODUCTION: Many regulations for aeromedical assessments state that a ratio between forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) of < 0.7 should be evaluated by a pulmonary specialist. The Global Lung Initiative (GLI) reference values introduced the lower limit of normal (LLN 2.5), in which the lowest 2.5% of the population is regarded as abnormal, instead of a fixed ratio. This study assesses the impact of adopting GLI reference values on aeromedical evaluation and referrals.METHODS: The Royal Netherlands Air Force performed 7492 aeromedical assessments between February 2012 and April 2017. Cases with FEV1/FVC < 0.7 from three groups were selected: 1) men < 25 yr; 2) men > 40 yr; and 3) women, with twice as many matched controls. Pearson's Chi-squared and Fisher’s exact tests were used to analyze the data.RESULTS: From the database, 23 (group 1), 62 (group 2), and 7 (group 3) cases were selected, with 184 controls. Respectively, 17%, 84%, and 29% would not be referred using the GLI. In the controls, this would lead to one additional referral (group 1). Qualitative analysis of the cases who would not be referred using the GLI showed that no significant diagnoses would have been missed.DISCUSSION: Using the GLI LLN 2.5 reference values for pulmonary function tests leads to significantly fewer referrals to a pulmonary specialist without missing relevant pulmonary pathology in our aircrew. This would reduce resources spent on the assessment of aircrew without compromising flight safety.Wingelaar-Jagt YQ, Wingelaar TT, Bülbül M, vd Bergh PP, Frijters E, Staudt E. The effect of using the lower limit of normal 2.5 in pulmonary aeromedical assessments. Aerosp Med Hum Perform. 2020; 91(8):636–640.

WOS: 000440125700023, 2-Amino-6-sulfamoylbenzothiazole (SMABT) and its proton transfer compound (HSMABT)(+)(HDPC)(-) (1) with 2,6-pyridinedicarboxylic acid (H2DPC), and their Cu(II) complexes (2 of SMABT, 3 and 4 of 1) have been prepared and characterized by spectroscopic techniques. Additionally, single crystal X-ray diffraction techniques were applied to all complexes. All compounds, including acetazolamide (AAZ) as the control compound, were also evaluated for their in vitro inhibition effects on human hCA I and hCA II for their hydratase and esterase activities. The synthesized complexes have remarkable inhibitory effects on hCA I and hCA II isoenzymes. The inhibition potentials of the proton transfer salt (1) and the metal complexes (2-4) are comparable with AAZ. Esterase K-i values of the compounds (1-4) are in the range of 0.089 +/- 0.008 mu M-0.149 +/- 0.017 mu M for hCA I and 0.046 +/- 0.008 mu M-0.085 +/- 0.019 mu M for hCA II. Inhibition data have been analyzed by using a one-way analysis of variance for multiple comparisons (p < 0.0001). (C) 2018 Published by Elsevier Ltd., Dumlupinar University Research Fund [2014/18]; Aksaray University of Science and Technology Application and Research Center [2010K120480], The authors acknowledge the support provided by Dumlupinar University Research Fund (grant No. 2014/18). In addition, the authors acknowledge Aksaray University of Science and Technology Application and Research Center, for the use of the Bruker SMART BREEZE CCD diffractometer (purchased under grant No. 2010K120480 of the State of Planning Organization).

In this study, we synthesized magnetic nanoparticles (MNPs) by co-precipitation method. After that, silica coating with tetraethyl orthosilicate (TEOS) (SMNPs), amine functionalization of silica coated MNPs (ASMNPs) by using 3-aminopropyltriethoxysilane (APTES) were performed, respectively. After activation with glutaraldehyde (GA) of ASMNPs, human carbonic anhydrase (hCA I) was immobilized on ASMNPs. The characterization of nanoparticles was performed by transmission electron microscopy (TEM), fourier transform infrared spectroscopy (FT-IR), X-ray powder diffraction (XRD) and vibrating sample magnetometer (VSM). The immobilization conditions such as GA concentration, activation time of support with GA, enzyme amount, enzyme immobilization time were optimized. In addition of that, optimum conditions for activity, kinetic parameters ( K m , V max , k cat , k cat/ K m ), thermal stability, storage stability and reusability of immobilized enzyme were determined. The immobilized enzyme activity was optimum at pH 8.0 and 25 °C. The K m value of the immobilized enzyme (1.02 mM) was higher than the free hCA I (0.48 mM). After 40 days incubation at 4 °C and 25 °C, the immobilized hCA I sustained 89% and 85% of its activity, respectively. Also, it sustained 61% of its initial activity after 13 cycles. Such results revealed good potential of immobilized enzyme for various applications.

WOS: 000392591100016, PubMed: 28100079, A novel proton transfer compound (SMHABT) (+)(HDPC)(-) (1) obtained from 2-amino-6-sulfamoylbenzothiazole (SMABT) and 2,6-pyridinedicarboxylic acid (H2DPC) and its Fe(III), Co(II), Ni(II) complexes (2-4), and Fe(II) complex of SMABT (5) have been prepared and characterized by spectroscopic techniques. Additionally, single crystal X-ray diffraction techniques were applied to complexes (2-4). All complexes (2-4) have distorted octahedral conformations and the structure of 5 might be proposed as octahedral according to spectral and analytical results. All compounds, including acetazolamide (AAZ) as the control compound, were also evaluated for their in vitro inhibition effects on human hCA I and hCA II for their hydratase and esterase activities. The synthesized compounds have remarkable inhibitory activities on hCA I and hCA II. Especially, the inhibition potentials of the salt and the metal complexes (1-5) are comparable with AAZ. Inhibition data have been analyzed by using a one-way analysis of variance for multiple comparisons (p < .0001)., Dumlupinar University Research Fund [2014/18], This work was supported by the Dumlupinar University Research Fund [(grant No. 2014/18)].

WOS: 000342056900013, PubMed ID: 24148087, A novel proton transfer compound (HMeOABT) (+) (HDPC)(-) (1) and its Fe(III), Co(II), Ni(II) and Cu(II) complexes (2-5) have been prepared and characterized by spectroscopic techniques. Complex 4 has distorted octahedral conformation revealed by single crystal X-ray diffraction method. Structures of the other complexes might be proposed as octahedral according to experimental data. All compounds were also evaluated for their in vitro inhibition effects on hCA I and II for their hydratase and esterase activities. Although there is no inhibition for hydratase activities, all compounds have inhibited the esterase activities of hCA I and II. Data have been analyzed by using a one-way analysis of variance. The comparison of the inhibition studies of 1-5 to parent compounds indicates that 1-5 have superior inhibitory effects. The inhibition effects of 2-5 are also compared to inhibitory properties of the metal complexes of MeOABT and H2DPC, revealing an improved transfection profile., Dumlupinar University Research Fund [2012/16], The authors acknowledge the support provided by Dumlupinar University Research Fund (grant No. 2012/16). The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

WOS: 000322938100008, A novel proton transfer compound (HMeABT)(+)(HDPC)(-)center dot H2O (1) obtained from 2-amino-6-methylbenzothiazole (MeABT) and dipicolinic acid (H2DPC) and its Fe(III), Fe(II), Co(II), Ni(II) and Cu(II) complexes (2-6) have been prepared and characterized by elemental, spectral (H-1 NMR, IR and UV-Vis) and thermal analyses, magnetic measurement and molar conductivity. Additionally, single crystal X-ray diffraction techniques were applied to all complexes. All compounds, including acetazolamide (AAZ) as the control compound, were also evaluated for their in vitro inhibition effects on human carbonic anhydrase isoenzymes (hCA I and hCA II) for their hydratase and esterase activities. Although there is no inhibition for hydratase activities, all compounds have inhibited the esterase activities of hCA land II. The comparison of the inhibition studies of 1-6 to parent compounds, MeABT and H2DPC, indicates that 1-6 have more inhibitory effects. The inhibition effects of 2-6 are also compared to the simple metal complexes of MeABT and H2DPC, and the complexes from proton transfer salt (2-6) have shown better inhibition effects. Nevertheless, all the studied compounds have less inhibition effects than AAZ, Dumlupinar University Research Fund [2010/2], The authors acknowledge the support provided by Dumlupinar University Research Fund (grant No. 2010/2). In addition, the authors would like to thank the Medicinal Plants and Medicine Research Center of Anadolu University Eskisehir for allowing to use the X-ray facility.

Mannich bases 2a-f derived from 3,4-dimethylphenol (1), formaldehyde and different amines are prepared and subjected to spectral (IR, 1H and 13C NMR) and elemental analyses. The inhibition of two human carbonic anhydrase (hCA, EC 4.2.1.1) isozymes I and II, with 1 and synthesized Mannich bases 2a-f and acetazolamide (AAZ) as a control compound was investigated in vitro by using the hydratase and esterase assays. In relation to hydratase and esterase activities of the half maximal inhibitory concentration (IC50) and the inhibition equilibrium constants (Ki)values were determined. Only two compounds (2a and 2e)exhibit weak hCA II inhibitory effects on esterase activity. IC50 and Ki values for 2a and 2e with respect to esterase activity of hCA II are0.88 × 103 and 6.3-7.6 µM and 0.44 × 103 and 19.0-96.4 µM,respectively. On the contrary, compounds 2b and 2d might be used as CA activators due to increasing esterase activity of hCA I and hCA II isozymes. © 2013 Informa UK, Ltd., This work was supported by grant (Grant No: 2008-1) from the Dumlupınar University Research Foundation and carried out in the Department of Chemistry of the Dumlupınar University.

Novel dioxoacridine sulfonamide compounds were synthesized from reaction of cyclic 1,3-diketones, sulfanilamide (4-amino benzene sulfonamide) and aromatic aldehydes. The structures of these compounds were confirmed by using spectral analysis (IR, H-NMR, 13C-NMR, and mass). Human carbonic anhydrase isoenzymes (hCA I and hCA II) were purified from erythrocyte cells by affinity chromatography. The inhibitory effects of sulfanilamide, acetazolamide (AAZ), and newly synthesized sulfonamides on hydratase and esterase activities of these isoenzymes have been studied in vitro. The IC50 values of compounds for esterase activity are 0.710.11 M for hCA I and 0.450.12 M for hCA II, respectively. The Ki values of these inhibitors were determined as 0,380,008 M for hCA I and 0,190,001 M for hCA II, respectively. © 2012 Informa UK, Ltd., Fundamental Research Fund of Shandong University: 2008-4, The authors are very grateful to Dumlupinar University Research Fund for providing financial support for this project (Grant No. 2008-4).

Three novel metal complexes of N-[5-(aminosulfonyl)-1,3,4-thiadiazol-2-yl]-4-benzoyl-1-(3-nitrophenyl)-5-phenyl-1H-pyrazole-3-carboxamide which possess strong carbonic anhydrase (CA) inhibitory properties have been synthesised. The structure of these compounds has been investigated by elemental analysis, FT-IR, LC/MS, UV-vis spectrophotometric method and magnetic susceptibility. Human carbonic anhydrase isoenzymes hCA-I and hCA-II were purified from erythrocyte cells by the affinity chromatography. The inhibitory effects of newly synthesized complexes and acetazolamide (AAZ) as a control compound on hydratase and esterase activities of these isoenzymes have been studied in vitro by comparing IC50 and Ki values and it has been found that the newly synthesised complexes behave as very powerful inhibitors against hCA-I and hCA-II than parent ligand (1) and than AAZ. © 2013 Informa UK, Ltd., National Council for Scientific Research, This work was supported by The Scientific and Research Council of Turkey (TÜBİTAK) with Grant No. TBAG-104T406.

Two novel proton transfer compounds were prepared between 2,4-dichloro-5-sulphamoylbenzoic acid (lasamide) (Hsba) and ethylenediamine (en), namely ethane-1,2-diaminium 2,4-dichloro-5-sulphamoylbenzoate (1), and also between Hsba and 2-amino-3-methylpyridine (2-amino-3-picoline) (amp), namely 2-amino-3-methylpyridinium 2,4-dichloro-5-sulphamoylbenzoate (2). All these were characterised by elemental, spectral (IR and UV-vis), thermal analyses, and single crystal X-ray diffraction studies. Compounds 1 and 2 crystallised in the P-1 and P21/c space groups, respectively. Intermolecular non-covalent interactions, such as ion pairing, hydrogen bonding, and ?Ï€-?Ï€ stacking were observed for these ionic compounds. The free ligands Hsba, en and amp, the products 1 and 2, and acetazolamide (AAZ) as the control compound, were also evaluated for their in vitro inhibitor effects on the human carbonic anhydrase isoenzymes (hCA I and hCA II) purified from erythrocyte cells by affinity chromatography for their hydratase and esterase activities. The half maximal inhibitory concentration (IC50) values for products 1 and 2 with respect to hydratase activity are 0.15 and 0.32 µ M for hCA I and 0.06 and 0.15 µ M for hCA II, respectively. The IC50 values of the same inhibitors for esterase activity are 0.13 and 0.8 µ M for hCA I and 0.14 and 0.1 µ M for hCA II, respectively. In relation to esterase activities, the inhibition equilibrium constants (Ki) were also determined and found to be 0.137 and 0.99 µ M on hCA I and 0.157 and 0.075 µ M on hCA II for 1 and 2, respectively. The comparison of the inhibition studies of the newly synthesised compounds 1 and 2 to the parent compounds Hsba and amp and also to AAZ indicated that 1 and 2 have an effective inhibitory activity on hCA I and II, and might be used as potential inhibitors. © 2011 Informa UK, Ltd., Faculty of Arts and Sciences 2007/2, The authors acknowledge the support provided by Dumlupınar University Research Fund (grant No. 2007/2). In addition, the authors would like to thank the Faculty of Arts and Sciences, Ondokuz Mayıs University, Turkey, for use of the Stoe IPDS-2 diffractometer purchased under grant F.279 of the University Research Fund.

A proton transfer compound, (Hamp)+(Hdipic)- 1.5H2O (1), and Cu(II) complexes, Cu(dipic)(amp)(H2O)] . [Cu(dipic)(amp)] . H2O.CH3COOH (2) and [Cu(dipic)(amp)Cu(dipic) (amp)(H2O)Cu(dipic)(amp)(H2O)] .3H2O (3), have been synthesized from 2,6-pyridinedicarboxylic acid (H2dipic) and 2-amino-4-methylpyridine (amp). They have been characterized by elemental, spectral (1H-NMR, IR, and UV-Vis), and thermal analyses. In addition, magnetic measurements and single crystal X-ray diffraction have been applied to 2 and 3. The crystal structure of 2 consists of two independent and different cationic sites with Cu2+ ions. Cu1 is four-coordinate in a distorted square planar geometry and Cu2 is five-coordinate in a distorted square pyramid. Compound 3 has three independent and different cationic sites of Cu2+ ions. Cu1 is four-coordinate in a distorted square planar geometry and Cu2 and Cu3 have fivecoordinate, distorted square-pyramidal sites. Inhibitory effects of 1, 2, and 3 have been studied and compared with starting compounds (amp and H2dipic) on bacterial growth of Staphylococcus aureus and Escherichia coli cultures. Compounds 2 and 3 prevent bacterial growth although 1 has no effect. Compounds 2 and 3 are more effective than amp and H2dipic, at similar concentrations on preventing bacterial growth for both organisms. © 2011 Taylor & Francis., Fundamental Research Fund of Shandong University Faculty of Arts and Sciences Ondokuz Mayis Üniversitesi 2007/2, The authors gratefully acknowledge the support provided by Dumlup|nar University, Turkey (under grant no. 2007/2 of the University Research Fund). The also thank the Faculty of Arts and Sciences, Ondokuz Mayis University, Turkey, for using the Stoe IPDS-2 diffractometer purchased under grant F.279 of the University Research Fund.

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).

A novel amino salicylato salt, 2-amino-6-methylpyridinium 2-hydroxy-5-sulfonatobenzoate (1), and its Cu(II) complex, 2-ammonio-6- methylpyridinium bis(µ6-5-sulfonatosalicylatoaquacopper(II)) (2), have been synthesized from free ligands, namely 5-sulfosalicylic acid (H 3ssa) and 2-amino-6-methylpyridine (amp). Compounds 1 and 2 have been characterized by elemental, spectral (1H NMR, IR and UV-Vis) and thermal analyses. Additionally, magnetic measurements and the single crystal X-ray diffraction technique have been applied to compound 2. Compound 2 crystallizes in the triclinic P1¯ space group. In the symmetric unit, the Cu(II) ion exhibits a distorted square planar configuration, coordinated by two carboxylate oxygen atoms (O2 and O2i), one phenolic oxygen atom (O1) of the ssa3- anion and a water molecule (O1w). The free ligands H3ssa and amp, and the products 1 and 2, and acetazolamide (AAZ) as a control compound have been also evaluated for their in vitro inhibitor effects on human carbonic anhydrase isoenzymes (hCA I and hCA II), purified from the erythrocyte cell by affinity chromatography for their hydratase and esterase activities. In relation to esterase activities, the inhibition equilibrium constants (Ki) have also been determined. A comparison of the inhibition studies of the newly synthesized compounds 1 and 2 with the parent compounds H 3ssa and amp, and to AAZ, indicates that 1 and 2 have an effective inhibitory activity on hCA I and II, and can be used as potential inhibitors.© 2010 Elsevier Ltd. All rights reserved., 2007/2 Faculty of Arts and Sciences Ondokuz Mayis Üniversitesi, The authors acknowledge the support provided by Dumlupinar University Research Fund (grant No. 2007/2 ). In addition, the authors would like to thank the Faculty of Arts and Sciences, Ondokuz Mayis University, Turkey, for use of the Stoe IPDS-2 diffractometer purchased under grant F.279 of the University Research Fund. Appendix A

[No abstract available]

Pyrazole carboxylic acid derivatives of 5-amino-1,3,4-thiadiazole-2- sulfonamide (inhibitor 1) were synthesized from ethyl 3-(chlorocarbonyl)-1-(3- nitrophenyl)-5-phenyl-1H-pyrazole-4-carboxylate compound. The inhibitory effects of inhibitor 1, acetazolamide (AAZ) and of 11 newly synthesized amides (5a-b, 6, 7a-g, and 8) on hydratase and esterase activities of carbonic anhydrase isoenzymes (hCA-I and hCA-II) have been studied in vitro. The comparison of newly synthesized amides to inhibitor 1 and to AAZ indicated that the new derivatives inhibit CA isoenzymes and they are more potent inhibitors than the parent inhibitor 1 and AAZ. © 2010 Elsevier Masson SAS. All rights reserved., Türkiye Bilimsel ve Teknolojik Araştirma Kurumu: 106T180 National Council for Scientific Research, This study was funded by The Scientific and Research Council of Turkey (TÜBITAK) with Grant No 106T180 .

WOS: 000273613500047 PubMed: 20006931 A novel proton transfer compound, pyridin-2-ylmethanaminium 2,4-dichloro-5-sulfamoylbenzoate ( 1), and a mixed-ligand Zn(II) complex, bis(2,4-dichloro-5-sulfamoylbenzoate)(2-aminomethylpyridine) aquazinc(II) monohydrate ( 2), have been synthesized from the same free ligands, which are 2,4-dichloro-5-sulfamoylbenzoic acid (Hsba) and 2-aminomethylpyridine ( amp). They have been characterized by elemental, spectral (H-1 NMR, IR and UV-vis.) and thermal analyses. Additionally, magnetic measurement and single crystal X-ray diffraction technique were applied to compound 2. In the complex, Zn( II) ion exhibits a distorted octahedral configuration coordinated by O1 and O1(i) atoms of two mono dentante sba anions and N1, N2, N2(i) atoms of bidentante amp anion and a water molecule (O1w). The free ligands Hsba and amp, and the products 1 and 2, and acetazolamide (AAZ) as the control compound, were also evaluated for their in vitro inhibitor effects on human Carbonic Anhydrase isoenzymes (hCA I and hCA II) purified from erythrocyte cell by affinity chromatography for their hydratase and esterase activities. The IC50 values of products 1 and 2 for hydratase activity are 0.26 and 0.13 mu M for hCA I and 0.30 and 0.15 mu M for hCA II, respectively. The IC50 values of the same inhibitors for esterase activity are 0.32 and 0.045 mu M for hCA I and 0.29 and 0.23 mu M for hCA II, respectively. In relation to esterase activities, the inhibition equilibrium constants (K-i) were also determined and found 0.25 and 0.058 mu M on hCA I and 0.22 and 0.24 mu M on hCA II for 1 and 2, respectively. The comparison of the inhibition studies of newly synthesized compounds 1 and 2 to parent compounds Hsba and amp and to AAZ indicated that 1 and 2 have effective inhibitory activity on hCA I and II, and might be used potential inhibitors. (C) 2009 Elsevier Ltd. All rights reserved. Dumlupinar University Research FundDumlupinar University [2007/2]; Faculty of Arts and Sciences at Ondokuz Mayis University, TurkeyOndokuz Mayis University; University Research Fund [F. 279] The authors acknowledge the support provided by Dumlupinar University Research Fund ( Grant No. 2007/2). In addition, the authors would like to thank the Faculty of Arts and Sciences at Ondokuz Mayis University, Turkey, for use of the Stoe IPDS-2 diffractometer purchased under Grant F. 279 of the University Research Fund.

Pyrazole carboxylic acid amides of 5-amino-1,3,4-thiadiazole-2-sulfonamide 1 (inhibitor 1) were synthesized from 4-benzoyl-1-(4-nitrophenyl)-5-phenyl-1H-pyrazole-3-carbonyl chloride and 4-benzoyl-1-(3-nitrophenyl)-5-phenyl-1H-pyrazole-3-carbonyl chloride compounds. Human carbonic anhydrase isoenzymes (hCA-I and hCA-II) were purified from erythrocyte cells by the affinity chromatography. The inhibitory effects of inhibitor 1, acetazolamide (AAZ), and of 16 newly synthesized amides (8-11, 12a-f, 13a-c, 14a-b, and 15) on hydratase and esterase activities of these isoenzymes have been studied in vitro. The average IC50 values of the new compounds (8-11, 12a-f, 13a-c, 14a-b, and 15) for hydratase activity ranged from 3.25 to 4.75 µM for hCA-I and from 0.055 to 2.6 µM for hCA-II. The mean IC50 values of the same inhibitors for esterase activity were in the range of 2.7-6.6 µM for hCA-I (with the exception of inhibitor 10, which did not inhibit the esterase activity of hCA-I) and of 0.013-4.2 µM for hCA-II. The Ki values for new compounds (8-11, 12a-f, 13a-c, 14a-b, and 15) were observed well below that of the parent compound inhibitor 1 and were also comparable to that of AAZ under the same experimental conditions. The comparison of newly synthesized amides to inhibitor 1 and to AAZ indicated that the new derivatives preferentially inhibit hCA-II and are more potent inhibitors of hCA-II than the parent inhibitor 1 and AAZ. © 2009 Elsevier Ltd. All rights reserved., Türkiye Bilimsel ve Teknolojik Araştirma Kurumu National Council for Scientific Research, This study was funded by The Scientific and Research Council of Turkey (TÜBITAK) with Grant No. TBAG-2376 and 106T180.

In this study, the in vitro effects of some sulfonamide derivatives, which are carbonic anhydrase inhibitors, on the enzymes activities of glucose-6-phosphate dehydrogenase, 6-phospho gluconate dehydrogenase and glutathione reductase were investigated. For this purpose, these three enzymes were purified from human erythrocytes. Purification procedure composed of four steps; preparation of the hemolysate, ammonium sulfate precipitation, 2',5'-ADP Sepharose 4B affinity chromatography, and gel filtration chromatography on Sephadex G-200. 5-(3alpha-Hydroxy-5-beta-cholanamido)-1,3,4-thiadiazole-2-sulfonamide (1), 5-(3alpha,12alpha-Dihydroxy-5-beta-cholanamido)-1,3,4-thiadiazole-2-sulfonamide (2), 5-(3alpha,7alpha,12alpha-Trihydroxy-5-beta-cholanamido)-1,3,4-thiadiazole-2-sulfonamide (3), 5-(3alpha,Acetoxy-5-beta-cholanamido)-1,3,4-thiadiazole-2-sulfonamide (4), 5-(3alpha,7alpha,12alpha-Triacetoxy-5-beta-cholanamido)-1,3,4-thiadiazole-2-sulfonamide (5), 5-(3,7,12-Trioxo-5-beta-cholanamido)-1,3,4-thiadiazole-2-sulfonamide (6), acetazolamide, and dorzolamide were tested in this experiment. Compounds 3, 5, and dorzolamide showed inhibitory effects on the activity of 6-phosphogluconate dehydrogenase, and I(50) values and K(i) constants were calculated as 0.0601 mM, 0.00253 mM, and 1.41 mM and 0.0878 +/- 0.0274 mM, 0.0042 +/- 0.0009 mM, and 3.1446 +/- 0.2081 mM, respectively. Glutathione reductase was also inhibited by 1 and 2. I(50) values and K(i) constants were 0.0471 mM and 0.0723 +/- 0.0388 mM for 1 and 0.0045 mM and 0.0061 +/- 0.0014 mM, for 2. If these sulfonamide derivatives are proposed as drugs, some of which are being used in glaucoma treatment such as acetazolamide and dorzolamide, these results should be taken into consideration concerning via these enzymes.