Unsymmetrical Cysteine Disulfides as Carbonic Anhydrase Inhibitors

A small library of unsymmetrical cysteine disulfides as four aliphatic, three aromatic and one heteroaromatic were evaluated for their inhibition of two important carbonic anhydrase (CA) enzymes, namely human carbonic anhydrase isoenzymes I (hCA I) and II (hCA II). IC50 values were recorded in the low nanomolar range (8.6–18.3 nM for hCA I and 42.9–99.9 nM for hCA II). The inhibition activities were significantly superior to those of the clinically available CA inhibitor acetazolamide for hCA I, while only marginally inferior for hCA II. These results highlight the relevance of screening small molecules as potential CA inhibitors (CAIs).