CA XIII Inhibitors

Carbonic anhydrase inhibitors (CAIs) are a class of compounds that bind to the metal ion in the active site of carbonic anhydrase enzymes, which are critical for pH and carbon dioxide regulation in various tissues. The inhibition of these enzymes can result in a reduction in the catalysis of the hydration of carbon dioxide and dehydration of bicarbonate. CA XIII inhibitors are largely sulfonamide-based, as sulfonamides have the ability to coordinate with the zinc ion in the active site of carbonic anhydrases, impeding their function. These sulfonamide-based inhibitors include compounds such as acetazolamide, methazolamide, and dichlorophenamide, which are structurally similar and function by a similar mechanism of action. Acetazolamide and methazolamide are archetypal molecules within this class, and their mechanism involves direct coordination with the active site zinc ion, displacing the water molecule that is essential for enzyme catalysis. This disruption of the normal catalytic cycle of the enzyme leads to a decrease in enzyme activity. Other inhibitors such as dorzolamide and brinzolamide are specifically formulated for ocular applications and function via the same mechanism but are optimized for better ocular penetration and reduced systemic absorption. Beyond sulfonamides, several other molecule classes can inhibit carbonic anhydrases. For example, topiramate and zonisamide are monosaccharide derivatives that inhibit carbonic anhydrase by binding to the same enzymatic site. Although not primarily developed as carbonic anhydrase inhibitors, these compounds have been found to possess inhibitory activity towards the enzyme.