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

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?mu m for hCA-I and 0.213?+/-?0.015 and 0.833?+/-?0.021?mu m 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?mu m for hCA-I and 0.110?+/-?0.010 and 0.052?+/-?0.002?mu m 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?mu m on hCA-I and 0.078?+/-?0.002 and 0.363?+/-?0.015?mu m on hCA-II for 2 and 4, respectively. Conclusions The synthesized compounds 2 and 4 had effective inhibitory activity (P?