Sulfonamides and their isosters as carbonic anhydrase inhibitors

Molecules containing the sulfonamide group (R-SO2NH2) as well as its structurally related isosters, sulfamido (R-NH-SO2NH2) and sulfamato (R-O-SO2NH2), constitute the most important class of inhibitors acting on the metalloenzyme carbonic anhydrase (EC 4.2.1.1). Despite their presence in the literature, in general the reports lack of a clear and organic overview linking the main structural features of the clinically used inhibitors with the therapeutic aspects. The current review is intended to highlight the structural basis of the interactions of sulfonamide-like groups within the active site of the carbonic anhydrases and will summarize the clinical use of the most interesting molecules for the treatment of relevant pathologies, such as glaucoma, obesity, cancer and CNS-affecting diseases.