Synthesis of some new pyrazole sulfonamide derivatives and investigation of inhibition effects on human erythrocyte carbonic anhydrase isoenzymes

Carbonic anhydrase (CA) (E.C 4.2.1.1) is a metalloenzyme containing zinc ions in its active site, which provide the reversible catalysis of the reactions of carbon dioxide and water to bicarbonate and hydrogen in living things. This enzyme which having 16 isoenzymes is distributed in human eye tissues and various tissues. CA inhibitors are widely used in the treatment of glaucoma because they reduce the high intraocular pressure (IOP) caused by excessive secretion of aqueous humor. In this study, acyl chloride was obtained by reacting our starting compound 4-benzoyl-1,5-diphenyl-1H-pyrazole-3-carboxylic acid with SOCl2. New pyrazole-sulfonamide derivatives (1-9) were synthesized from the reaction of this compound with various sulfonamides. Structures of the obtained compounds, illuminated with the help of IR, 1H-NMR, and 13C-NMR spectra. Afterward, the inhibition properties of newly synthesized pyrazole sulfonamide derivative compounds (1-9) on hCA-I and hCA-II isoenzymes were investigated as in vitro. From the kinetic data the enzyme activities were determined. The esterase activities of the carbonic anhydrase enzyme were measured to determine the inhibitory effects of the compounds. IC50 values were calculated by plotting %Activity-Inhibitor plots and Ki constants were determined by plotting Lineweaver-Burk plots. Esterase IC50 values were found to be between 0.182-57.988 μM for hCA-I and between 0.023-6.410 μM for hCA-II, Ki values were also found to be between 0.052-41.530 μM for hCA-I and between 0.003-4.431 μM for hCA-II.