Carbonic anhydrase inhibitors. Schiff bases of some aromatic sulfonamides and their metal complexes: towards more selective inhibitors of carbonic anhydrase isozyme IV.
Reaction of three aromatic sulfonamides possessing a primary amino group, i.e., sulfanilamide, homosulfanilamide and p-aminoethyl-benzenesulfonamide with heterocyclic and aromatic aldehydes afforded a series of Schiff bases. Metal complexes of some of these Schiff bases with divalent transition ions such as Zn(II), Cu(II), Co(II) and Ni(II) have also been obtained. The new compounds were assayed as inhibitors of three isozymes of carbonic anhydrase (CA). Several of the new compounds showed a modest 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 generally possess a 17-33 times lower affinity for bCA IV. This greater selectivity toward bCA IV is due mainly to a slightly decreased potency against hCA II relative to classical inhibitors. However, metal complexes of these Schiff bases possessed an increased affinity for hCA II, being less inhibitory against bCA IV. The first type of compounds reported here (i.e., the Schiff bases of aromatic sulfonamides with heterocyclic aldehydes) might thus lead to the development of low molecular weight isozyme specific CA IV inhibitors. The difference in affinity for the three isozymes of the inhibitors reported by us here is tentatively explained on the basis of recent X-ray crystallographic studies of these isozymes and their adducts with substrates/inhibitors.
Popescu
A
A
Department of Organic Chemistry, Polytechnic University, Bucharest, Roumania.
Simion
A
A
Scozzafava
A
A
Briganti
F
F
Supuran
C T
CT
D000447:Aldehydes; D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis* / Q000378:metabolism*; D002256:Carbonic Anhydrases / Q000378:metabolism*; D006801:Humans; D006841:Hydrocarbons, Aromatic; D008024:Ligands; D008565:Membrane Proteins / Q000378:metabolism; D008670:Metals / Q000378:metabolism; D012545:Schiff Bases / Q000138:chemical synthesis* / Q000378:metabolism; D013053:Spectrophotometry; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000378:metabolism
D000447:Aldehydes; D002257:Carbonic Anhydrase Inhibitors; D006841:Hydrocarbons, Aromatic; D008024:Ligands; D008565:Membrane Proteins; D008670:Metals; D012545:Schiff Bases; D013449:Sulfonamides; D002256:Carbonic Anhydrases