Carbonic Anhydrase Inhibitors: Novel Compounds Containing S-NH Moieties: Sulfenamido-Sulfonamides, Sulfenimido-Sulfonamides and their Interaction with Isozymes I, II and IV

Abstract

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 hCAI, hCAII (human cytosolic forms from red cells) and bCAIV (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.

Key Words:

• Aromatic/heterocyclic sulfonamide
• Bis-sulfonamide
• Carbonic anhydrase
• Isozyme I, II, IV
• Sulfenamide
• Antiglaucoma agents