Abstract
The inhibition of delta- and eta-class carbonic anhydrases (CAs; EC 4.2.1.1) was poorly investigated so far. Only one delta-CA, TweCA from the diatom Thalassiosira weissflogii, and one eta-CA, PfCA, from Plasmodium falciparum, have been cloned and characterised to date. To enrich delta- and eta-CAs inhibition profiles, a panel of 22 phenols was investigated for TweCA and PfCA inhibition. Some derivatives showed effective, sub-micromolar inhibition of TweCA (K(I)s 0.81-65.4 mu M) and PfCA (K(I)s 0.62-78.7 mu M). A subset of compounds demonstrated a significant selectivity for the target CAs over the human physiologically relevant ones. This study promotes the identification of new potent and selective inhibitors of TweCA and PfCA, which could be considered as leads for finding molecular probes in the study of carbon fixation processes (in which TweCA and orthologue enzymes are involved) or drug candidates in the treatment of malaria.