Carbonic anhydrase inhibitors. Part 89 1 metal complexes of benzolamide with strong enzyme inhibitory and putative antiulcer properties

Complexes of the potent carbonic anhydrase (CA) sulfonamide inhibitor benzolamide (5-benzenesulfonamido-1,3,4-thiadazole-2-sulfonamide) and metal ions such as A1(III); Cd(II) and Pb(II) have been prepared, characterized by spectroscopic and analytic methods, and assayed for the inhibition of three CA isozymes, the cytosolic hCA I and hCA II, as well as the membrane-bound bCA IV (h = human, b = bovine source). Very affective inhibition against all these isozymes has been evidenced (in the low nanomolar range), making some of these complexes (such as the aluminum derivatives) atractive candidates for the development of clinically useful agents with potential gastric applications. One of the pepared compounds (8) showed important reduction of the gastric acid secretion parameters 3 days after administration in dogs with chronic gastric fistulas. Both BAO (the basal acid output), and MAO (the maximal acid output after stimulation with histamine) were drastically reduced in the animals treated with the Al(III) complex of benzolamde, 8, as compared to the same parametrs in animals that did not receive the enzyme inhibitor. These are promising results for the possible use of metal complexes of heterocyclic sulfonamides as treatment alternatives (alone or in combination with other drugs) for gastric acid secretion imbalances.