Carbonic anhydrase and matrix metalloproteinase inhibitors. Inhibition of human tumor-associated isozymes IX and cytosolic isozyme I and II with sulfonylated hydroxamates

A series of sulfonylated hydroxamates were synthesized and evaluated as dual inhibitors of both human carbonic anhydrases (hCAs) and matrix metalloproteinases (MMPs), two metalloenzyme families involved in carcinogenesis and tumor invasion processes. The new derivs. were tested on three CA isoenzymes, the cytosolic isoenzymes I and II, and the transmembrane, tumor-assocd. isoenzyme IX, and also on human gelatinases (MMP-2 and MMP-9). Some of the new derivs. proved to be potent and selective inhibitors of CA II, but only 2 compds., devoid of the arylsulfonyl moiety, proved to have a better inhibitory activity on hCA IX than on hCA I and II, in the micromolar range.