New series of sulfonamides containing amino acid moiety act as effective and selective inhibitors of tumor-associated carbonic anhydrase XII

Abstract

New benzenesulfonamides incorporating water solubilizing moieties were synthesized using N-α-acetyl-l-lysine or γ-aminobutyric acid as scaffolds followed by the conversion of their terminal amino group to the guanidine one. Their inhibition activity was assessed by determining their K_Is values against the human (h) carbonic anhydrase (CA, EC 4.2.1.1) isoforms hCA I, II, IX and XII. Some of these compounds were medium potency inhibitors of the cytosolic (CA I, II) and transmembrane (CA IX) isoforms and highly effective, nanomolar inhibitors of the second transmembrane isoform hCA XII. Some of these sulfonamides possessing good selectivity inhibition for the tumor-associated CA XII isoform over the cytosolic and physiologically dominant isoforms CA I and II may be used as tools to develop new anticancer agents.

• Amino acid
• carbonic anhydrase inhibitor
• sulfonamide
• tumor-associated CA XII

Declaration of interest

C.T.S. reports conflict of interest as author of many patents on CA inhibitors. The authors alone are responsible for the content and writing of this article. This project was funded by a 7th FP EU grant (METOXIA).