Carbonic anhydrase/COX-2 inhibitors in the treatment of various diseases

Abstract

The sulfonamides constitute an important class of drugs, with several types of clinically used agents, possessing antibacterial, anticarbonic anhydrase (CA), diuretic, hypoglycaemic, anti-thyroid, protease inhibitory, anticancer and cyclooxygenase (COX) inhibitory activities, among others. A recently developed class of such pharmacological agents, incorporating primary sulfamoyl moieties in their molecule, is constituted by the COX-2 selective inhibitors, with at least two clinically used drugs, celecoxib and valdecoxib, discovered by Pharmacia Corp. It was recently shown that the sulfonamide COX-2-selective inhibitors (but not the methylsulfone ones, such as rofecoxib developed by Merck and Co.) also act as nanomolar inhibitors of CAs, some of which are strongly involved in tumorigenesis. In consequence, the potent anticancer effects of the sulfonamide COX-2-selective inhibitors and the much weaker effects of rofecoxib, reported ultimately by many researchers, may be explained by the contribution of CA inhibition to such processes in addition to COX-2 inhibition. In these two patents, Pharmacia Corp. claim the use of their sulfonamide COX-2 inhibitory compounds (celecoxib, valdecoxib and their many congeners), alone or in combination with classical sulfonamide CA inhibitors (acetazolamide, methazolamide, dichlorophenamide, dorzolamide, brinzolamide and their congeners, as well as structurally-related derivatives) for the treatment of CA-mediated disorders, including glaucoma and neoplasia. The patents do not contain any experimental evidence for the potential use of such compounds/combinations for the management of these pathologies, but are based on literature data from other laboratories.

• acetazolamide
• brinzolamide
• carbonic anhydrase
• celecoxib
• cyclooxygenase-2 (COX-2)
• dorzolamide
• rofecoxib
• sulfonamide
• valdecoxib