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

Abstract

Abstract 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.