By using N-alpha-acetyl-L-lysine or GABA scaffolds and the conversion of the terminal amino group to the guanidine one, benzenesulfonamides incorporating water solubilizing moieties were synthesized. The new compounds were medium potency inhibitors of the cytosolic carbonic anhydrase (CA, EC 4.2.1.1) isoforms I and II, and highly effective, nanomolar inhibitors of the pathogenic bacterial alpha-CA from Vibrio cholerae. These sulfonamides possess good selectivity for inhibiting the bacterial over the mammalian isoforms and may be used as tools to understand the role of bacterial CAs in pathogenesis.
