Rahmi Kasımoğulları

Synthesis, characterization and antiglaucoma activity of some novel pyrazole derivatives of 5-amino-1,3,4-thiadiazole-2-sulfonamide.

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.

Facile synthesis and characterization of novel pyrazole-sulfonamides and their inhibition effects on human carbonic anhydrase isoenzymes.

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, (1)H NMR, (13)C NMR and LC-MS analysis. (1)H NMR and (13)C 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 K(i) 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.

Inhibitory effect of novel pyrazole carboxamide derivatives on human carbonic anhydrase enzyme

The synthesis, characterization and biological evaluation of novel pyrazole carboxamide derivatives (2–9) are presented. 1H and 13C NMR have been used for the structure description, possible tautomeric structures determination and hydrogen bonding observation. FT-IR results have confirmed the synthesis of the pyrazole derivatives while thermal gravimetric analysis has confirmed thermal stability up to 300°C. The melting temperatures are strongly dependent on their crystal structure as confirmed by differential scanning calorimetry and X-ray diffraction measurements. Impacts of 2–9 as possible antiglaucoma agents were investigated on carbonic anhydrase I and II (CA-I and II) isozymes purified from human erythrocytes in vitro. Compounds 3 and 9 had the highest inhibitory effect while compounds 6 and 8 showed the lowest inhibition.

Synthesis of 5-amino-1,3,4-thiadiazole-2-sulphonamide derivatives and their inhibition effects on human carbonic anhydrase isozymes

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.

Synthesis and characterization of metal complexes of heterocyclic sulfonamide as carbonic anhydrase inhibitors

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.

The synthesis of novel pyrazole-3,4-dicarboxamides bearing 5-amino-1,3,4-thiadiazole-2-sulfonamide moiety with effective inhibitory activity against the isoforms of human cytosolic carbonic anhydrase I and II

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, (1)H NMR, (13)C 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 Ki values were determined as 0.119-3.999μM for hCA I and 0.084-0.878μM for 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.

Synthesis and characterisation of novel Co(II) complexes of pyrazole carboxylate derivated of sulfonamide as carbonic anhydrase inhibitors

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.

Synthesis, characterization and in vitro inhibition of metal complexes of pyrazole based sulfonamide on human erythrocyte carbonic anhydrase isozymes I and II

Abstract 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.