Sulfonamide inhibition studies of the beta-carbonic anhydrase from the pathogenic bacterium Vibrio cholerae

The genome of the pathogenic bacterium Vibrio cholerae encodes for three carbonic anhydrases (CAs, EC 4.2.1.1) belonging to the alpha-, beta- and gamma-classes. VchCA, the alpha-CA from this species was investigated earlier, whereas the beta-class enzyme, VchCA beta was recently cloned, characterized kinetically and its X-ray crystal structure reported by this group. Here we report an inhibition study with sulfonamides and one sulfamate of this enzyme. The best VchCA beta inhibitors were deacetylated acetazolamide and methazolamide and hydrochlorothiazide, which showed inhibition constants of 68.2-87.0 nM. Other compounds, with medium potency against VchCA beta, (K(I)s in the range of 275-463 nM), were sulfanilamide, metanilamide, sulthiame and saccharin whereas the clinically used agents such as acetazolamide, methazolamide, ethoxzolamide, dorzolamide, zonisamide and celecoxib were micromolar inhibitors (K(I)s in the range of 4.51-8.57 mu M). Identification of potent and possibly selective inhibitors of VchCA and VchCA beta over the human CA isoforms, may lead to pharmacological tools useful for understanding the physiological role (s) of this under-investigated enzymes. (C) 2016 Elsevier Ltd. All rights reserved.