Synthesis of sulfonamides with effective inhibitory action against Porphyromonas gingivalis gamma-carbonic anhydrase

New benzenesulfonamides incorporating GABA or N-alpha-acetyl-L-lysine scaffolds as well as guanidine functionalities as water solubilizing moieties were obtained, using 4-aminoethyl/methyl-benzenesulfonamide and metanilamide/sulfanilamide as zinc-binding motives. The new compounds were medium potency inhibitors of the widespread cytosolic human carbonic anhydrase (CA, EC 4.2.1.1) isoforms I and II and more effective inhibitors (K(I)s low nanomolar range) of the bacterial gamma-CA from the oral pathogen Porphyromonas gingivalis. These sulfonamides may be useful tools for understanding the physiological role of bacterial CAs in pathogenesis of some infectious disease. (C) 2014 Elsevier Ltd. All rights reserved.