Synthesis of novel Sulfonamide Compounds based on 4-aminobenzenesulfonamide and investigation of carbonic anhydrase activity

In the current study new carbonic anhydrase inhibitors which candidates for glaucoma treatment was synthesized. For this purpose, firstly, 4-nitro-N-(4-sulfomoylphenyl)benzamide (3) was obtained from the reaction of 4-aminobenzene sulfonamide (1) and 4-nitrobenzoyl chloride (2). Later, compound 3 was reduced with Na2S.H2O, and 4-amino-N-(4-sulfamoylphenyl)benzamide (4) was obtained. Finally new sulfonamide derivatives, as carbonic anhydrase inhibitors, (6a-i) were synthesized with high yield (71%-90%) from the reactions of compound 4 and sulfonyl chloride derivatives (5a-i). The structures of these compounds were confirmed by using spectral analysis (FT-IR, 1H NMR, 13C-NMR (APT), LC/MS and HRMS). For investigate the inhibition effects of 6a-i on human carbonic anhydrase isoenzymes, hCA I and II were purified from human erythrocytes with Sepharose®4B-L-tyrosine-p-aminobenzene sulfonamide affinity chromatography and the inhibition effects of these compounds on the hydratase and esterase activities of the isozymes have been studied as in vitro, and, IC50 and Ki values were determined. The results were shown that newly synthesized compounds have quite powerful inhibitory properties. Anahtar kelimeler: Sulfonamide, Sulfonyl Chloride, Glaucoma, Carbonic Anhydrase.