Carbonic anhydrase inhibitors: novel compounds containing S-NH moieties: sulfenamido-sulfonamides, sulfenimido-sulfonamides and their interaction with isozymes I, II and IV.
Reaction of 2-nitrophenyl- and 4-nitrophenylsulfenyl chlorides with aromatic/heterocyclic sulfonamides/bis-sulfonamides containing a free amino, hydrazino or imino group afforded sulfenamido-sulfonamides, or sulfenimido-sulfonamides. Oxidation of these derivatives with potassium permanganate in acetone led to the corresponding bis-sulfonamides. The obtained compounds were assayed as inhibitors of the zinc enzyme carbonic anhydrase (CA), isozymes hCA I, hCA II (human cytosolic forms from red cells) and bCA IV (bovine membrane-associated form). Good inhibition of the three CA isozymes was observed with some of the new compounds, the bis-sulfonamides being more active than the sulfenamido-sulfonamides. Structure-active correlations for the new series of inhibitors are discussed. Some of the sulfenamido-sulfonamides (but not the corresponding bis-sulfonamides) showed topical intraocular pressure lowering effects when applied as a 2% solution directly into the rabbit eye.
Scozzafava
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Università degli Studi, Laboratorio di Chimica Inorganica e Bioinorganica, Firenze, Italy.
Supuran
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CT
D000818:Animals; D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002256:Carbonic Anhydrases / Q000187:drug effects* / Q000378:metabolism; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D007429:Intraocular Pressure / Q000187:drug effects; D008297:Male; D011817:Rabbits; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
D002257:Carbonic Anhydrase Inhibitors; D013449:Sulfonamides; D002256:Carbonic Anhydrases