Potent carbonic anhydrase I, II, IX and XII inhibition activity of novel primary benzenesulfonamides incorporating bis-ureido moieties

A novel series of twelve aromatic bis-ureido-substituted benzenesulfonamides was synthesised by conjugation of aromatic aminobenzenesulfonamides with aromatic bis-isocyanates. The obtained bis-ureido-substituted derivatives were tested against four selected human carbonic anhydrase isoforms (hCA I, hCA II, hCA IX and hCA XII). Most of the new compounds showed an effective inhibitory profile against isoforms hCA IX and hCA XII, also having some selectivity with respect to hCA I and hCA II. The inhibition constants of these compounds against isoforms hCA IX and XII were in the range of 6.73-835 and 5.02-429 nM, respectively. Since hCA IX and hCA XII are important drug targets for anti-cancer/anti-metastatic drugs, these effective inhibitors reported here may be considered of interest for cancer related studies in which these enzymes are involved.

Automated summary

By conjugating aromatic aminobenzenesulfonamides with aromatic bis-isocyanates, a series of twelve aromatic bis-ureido-substituted benzenesulfonamides was synthesized. These compounds showed effective inhibitory activity against four human carbonic anhydrase isoforms (hCA I, hCA II, hCA IX, and hCA XII), with selectivity towards hCA IX and hCA XII. The inhibition constants of these compounds ranged from 6.73-835 nM against hCA IX and 5.02-429 nM against hCA XII. Given the importance of hCA IX and hCA XII as drug targets for anti-cancer/anti-metastatic drugs, these inhibitors may have significance in cancer-related studies involving these enzymes.