Inhibition of α-, β-, γ-, and δ-carbonic anhydrases from bacteria and diatoms with N'-aryl-N-hydroxy-ureas

The inhibition of alpha-, beta-, gamma-, and delta-class carbonic anhydrases (CAs, EC 4.2.1.1) from bacteria (Vibrio cholerae and Porphyromonas gingivalis) and diatoms (Thalassiosira weissflogii) with a panel of N'-aryl-N-hydroxy-ureas is reported. The alpha-/beta-CAs from V. cholerae (VchC alpha and VchC beta) were effectively inhibited by some of these derivatives, with K(I)s in the range of 97.5 nM - 7.26 mu M and 52.5 nM - 1.81 mu M, respectively, whereas the beta-class enzyme VchC gamma was less sensitive to inhibition (K(I)s of 4.75 - 8.87 mu M). The beta-CA from the pathogenic bacterium Porphyromonas gingivalis (PgiC beta) was not inhibited by these compounds (K(I)s > 10 mu M) whereas the corresponding gamma-class enzyme (PgiC gamma) was effectively inhibited (K(I)s of 59.8 nM - 6.42 mu M). The beta-CA from the diatom Thalassiosira weissflogii (TweC delta) showed effective inhibition with these derivatives (K(I)s of 33.3 nM - 8.74 mu M). As most of these N-hydroxyureas are also ineffective as inhibitors of the human (h) widespread isoforms hCA I and II (K(I)s > 10 mu M), this class of derivatives may lead to the development of CA inhibitors selective for bacterial/diatom enzymes over their human counterparts and thus to anti-infectives or agents with environmental applications.