Inhibition of the β-carbonic anhydrase from the protozoan pathogen Trichomonas vaginalis with sulphonamides

Sulphonamides and their isosteres are classical inhibitors of the carbonic anhydrase (CAs, EC 4.2.1.1) metalloenzymes. The protozoan pathogen Trichomonas vaginalis encodes two such enzymes belonging to the beta-class, TvaCA1 and TvaCA2. Here we report the first sulphonamide inhibition study of TvaCA1, with a series of simple aromatic/heterocyclic primary sulphonamides as well as with clinically approved/investigational drugs for a range of pathologies (diuretics, antiglaucoma, antiepileptic, antiobesity, and antitumor drugs). TvaCA1 was effectively inhibited by acetazolamide and ethoxzolamide, with K(I)s of 391 and 283 nM, respectively, whereas many other simple or clinically used sulphonamides were micromolar inhibitors or did not efficiently inhibit the enzyme. Finding more effective TvaCA1 inhibitors may constitute an innovative approach for fighting trichomoniasis, a sexually transmitted infection, caused by T. vaginalis.

Automated summary

Sulphonamides have been found to effectively inhibit the TvaCA1 enzyme, suggesting a potential new approach for combating trichomoniasis. Acetazolamide and ethoxzolamide were identified as the most effective inhibitors, while other sulphonamides tested showed weaker inhibition or were not efficient in inhibiting TvaCA1.