Carbonic anhydrase inhibitors .50. Interaction of isozymes I and II of carbonic anhydrase with Ge(IV) and Sb(III) derivatives

The interaction of carbonic anhydrase (CA) isozymes I and II with a series of Ge(IV) and Sb(III) derivatives containing among others arylsulfonylamido moieties in their molecule was investigated kinetically and spectrophotometrically, utilizing the native and Co(II)-substituted enzymes. Depending on the substitution pattern at the germanium/antimony and the sulfonamide nitrogen atoms, moderately active inhibitors as well as inactive compounds were detected. The active derivatives constitute a novel class of CA inhibitors that bind to the metal ion at the enzyme active site, as proved by changes in the electronic spectra of adducts of such inhibitors with Co(II)CA. Similarly to the prototypical inhibitors of CAs, the aromatic/heterocyclic sulfonamides, the new inhibitors are of the non-competitive type when 4-nitrophenyl acetate is used as the substrate.