Carbonic anhydrase inhibitors. Part 37. Novel classes of isozyme I and II inhibitors and their mechanism of action. Kinetic and spectroscopic investigations on native and cobalt-substituted enzymes

Article abstract of DOI:10.1016/S0223-5234(97)86179-X

The interaction of Zn(II)- and Co(II)-carbonic anhydrase (CA) with a series of compounds possessing moieties resembling the aromatic sulfonamides, such as sulfamide, sulfamic acid, N-substituted aromatic sulfonamides, sulfenamides, sulfinic and seleninic acids, was investigated using kinetic and spectroscopic techniques. All these compounds inhibit the hydrasic and esterasic activity of the enzyme. Their binding within the active site of isozymes I and II is discussed on the basis of modifications of electronic and ¹H-NMR spectra of their adducts with the Co(II) enzyme. Some of these compounds represent novel classes of CA inhibitors, possessing equal or stronger potencies than the prototypical inhibitors, the unsubstituted sulfonamides. Qualitative structure-activity correlations are discussed.