Ricerc@Sapienza

We discovered novel and selective sulfonamides/amides acting as inhibitors of the a-carbonic anhydrase
(CA, EC 4.2.1.1) from the pathogenic bacterium Vibrio cholerae (VchCA). This Gram-negative bacterium is
the causative agent of cholera and colonises the upper small intestine where sodium bicarbonate is present
at a high concentration. The secondary sulfonamides and amides investigated here were potent, low
nanomolar VchCA inhibitors whereas their inhibition of the human cytosolic isoforms CA I and II was in

Among human carbonic anhydrase (CA) inhibitors, the α,γ-diketocarboxylic acids and esters are still poorly investigated. Here, we report the first compounds of this class (1-6) acting as potent inhibitors at low nanomolar level against the cancer-related human CA IX and XII, and 2-3 magnitude orders selective toward the cytosolic isoforms hCA I and II. At enzymatic level, the α,γ-diketoacids 1-3 were more effective inhibitors compared to the corresponding ethyl esters 4-6.

We report here the synthesis and human carbonic anhydrases (CA, EC 4.2.1.1) inhibitory properties of a series of 4′-substituted 1,1′-biphenyl-4-sulfonamides incorporating a 2″- or 3″-amino- or carboxyphenyl unit. Most compounds showed significant variations in their inhibition profiles against CA II and IX when compared to previously reported analogs 12–18 bearing a 4″-amino or a 4″-carboxy group.