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A newly described β-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 × 10⁵ s -1 and a k cat /K m of 8.9 × 10⁷ M -1 s -1 ). A panel of sulphonamides 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 β-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.

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