Carbonic anhydrase inhibitors and their therapeutic potential

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Abstract
Carbonic anhydrases (CAs, EC 4.2.1.1) are wide-spread zinc enzymes, present in archaeo- and eubacteria, algae, green plants and animals. Within these organisms CAs are encoded by three distinct, evolutionarily unrelated gene families: the α-CA, the β-CA and the γ-CA families, respectively. These enzymes are very efficient catalysts for the reversible hydration of CO2 to bicarbonate; the α-CAs possess high versatility, being able to catalyse other hydrolytic processes. It is not known whether other reactions catalysed by CAs (than the hydration of CO2/dehydration of HCO-) may have physiological relevance in systems where these enzymes are present. CAs are inhibited primarily by two main classes of compounds: the metal complexing inorganic anions (e.g., cyanide, cyanate, thiocyanate, azide, hydrogensulphide etc.) and the unsubstituted sulphonamides possessing the general formula RSO2NH2 (R = aryl; hetaryl; perhaloalkyl). The first type of inhibitor was important for understanding in detail the catalytic and...