New hydroxypyrimidinone-containing sulfonamides as carbonic anhydrase inhibitors also acting as MMP inhibitors

A set of benzenesulfonamide (BSA) derivatives bearing a hydroxypyrimidinone (HPM) moiety were synthesized and investigated for their inhibitory activity against several carbonic anhydrase (CA, EC 4.2.1.1) isozymes. They all revealed to be very potent inhibitors (nanomolar order) of the cytosolic CA I and II isozymes, but especially of the transmembrane, tumor-associated CA IX isozyme, a beneficial feature for a potential antitumor effect of these compounds. Further structure optimization aimed at improving the specificity of CA inhibition and enhancing their matrix metalloproteinase (MMP) inhibitory activity may also lead to new compounds with an attractive dual mechanism of action as antitumor agents.