Sulfonamide Inhibition Studies of a New β-Carbonic Anhydrase from the Pathogenic Protozoan Entamoeba histolytica

A newly described -carbonic anhydrase (CA, EC 4.2.1.1) from the pathogenic protozoan Entamoeba histolytica, EhiCA, was recently shown to possess a significant catalytic activity for the physiologic CO2 hydration reaction (k(cat) of 6.7 x 10(5) s(-1) and a k(cat)/K-m of 8.9 x 10(7) M-1 s(-1)). A panel of sulfonamides and one sulfamate, some of which are clinically used drugs, were investigated for their inhibitory properties against EhiCA. The best inhibitors detected in the study were 4-hydroxymethyl/ethyl-benzenesulfonamide (K(I)s of 36-89 nM), whereas some sulfanilyl-sulfonamides showed activities in the range of 285-331 nM. Acetazolamide, methazolamide, ethoxzolamide, and dichlorophenamide were less effective inhibitors (K(I)s of 509-845 nM) compared to other sulfonamides investigated here. As -CAs are not present in vertebrates, the present study may be useful for detecting lead compounds for the design of more effective inhibitors with potential to develop anti-infectives with alternative mechanisms of action.