CARBONIC-ANHYDRASE INHIBITORS - INHIBITION OF ISOZYME-I, ISOZYME-II AND ISOZYME-IV WITH HETEROCYCLIC MERCAPTANS, SULFENAMIDES, SULFONAMIDESAND THEIR METAL-COMPLEXES

A series of sulfenamides, sulfonamides and sulfonamide metal complexes have been prepared starting from 4,5-disubstituted-3-mercapto-1,2,4-t riazole derivatives. The heterocyclic mercaptans were oxidized to the corresponding sulfenamides by hypochlorite in the presence of ammonia. The sulfonamides were obtained by oxidation of sulfenamides with pota ssium per manganate. The Zn(II) and Cu(II) complexes of the new hetero cyclic sulfonamides have been prepared via the sodium salt of the liga nd. Inhibition of three carbonic anhydrase (CA) isozymes, hCA I, hCA I I and bCA IV (h = human, b = bovine) with the prepared compounds has b een investigated. Mercaptans were generally less inhibitory than sulfe namides, which in turn behaved as weaker inhibitors than the sulfonami des. The strongest inhibitors were the Zn(II) and Cu(II) complexes of the heterocyclic sulfonamides. Susceptibility to inhibition was genera lly: hCA II > bCA IV > hCA I. Although none of the obtained simple inh ibitors (mercaptans, sulfenamides, sulfonamides) possessed antiglaucom a action when administered directly into the eye in experimental anima ls, the Zn(II) and Cu(II) complexes of some sulfonamides acted as more efficient intraocular pressure lowering agents as compared to the cli nical drug dorzolamide. This constitutes an encouraging result for obt aining novel antiglaucoma drugs from this class of CA inhibitors.