Carbonic anhydrase inhibitors. Part 43. Schiff bases derived from aromatic sulfonamides: towards more specific inhibitors for membrane-bound versus cytosolic isozymes

Abstract

Summary Schiff bases were prepared by reaction of sulfanilamide, homosulfanilamide and p -aminoethyl-benzenesulfonamide with substituted benzene and heterocyclic aldehydes. The compounds were characterized by standard procedures and were assayed as inhibitors of three isozymes of carbonic anhydrase (CA). Several of these new compounds showed a modest two-fold selectivity for the membrane-bound (bovine) isozyme, CA IV (bCA IV) as compared to the cytosolic human isozymes hCA I and II, in contrast to classical inhibitors which are 17–33 times less effective against bCA IV. This greater selectivity toward bCA IV is due mainly to a decreased potency against hCA II relative to classical inhibitors. This type of compound might lead to the development of low molecular weight isozyme specific CA IV inhibitors.