Novel pyrazole-3,4-dicarboxamides bearing biologically active sulfonamide moiety as potential carbonic anhydrase inhibitors

Abstract

In this study a series of pyrazole-3,4-dicarboxamide (3–10) derivatives bearing sulfonamide moiety were synthesized starting from 1-(3-nitrophenyl)-5-phenyl-1H-pyrazole-3,4-dicarboxylic acid (1). The structures of synthesized molecules were characterized by FT-IR, 1H NMR, 13C NMR, and elemental analysis methods. Human carbonic anhydrase isoenzymes (hCA I and hCA II) were purified separately from erythrocyte cells by the Sepharose-4B-L-tyrosine-sulfanilamide affinity column chromatography and inhibitory effects of newly synthesized sulfonamides on esterase activities of these isoenzymes have been studied as in vitro. The Ki values of compounds were found in the range of 0.056–110.400 μM for hCA I and 0.057–533.400 μM for hCA II. Compound 4 has the highest inhibitory effect for hCA I and hCA II while compound 5 showed lowest inhibition. The structure–activity relationships for the inhibition of these isoforms with the pyrazole-sulfonamides reported here were also elucidated. Keywords: Pyrazole, Pyrazole-3,4-dicarboxamide, Synthesis, Reduction, Carbonic anhydrase, Enzyme inhibition