Sulfonamide inhibition studies of the b carbonic anhydrase from the newly discovered bacterium Enterobacter sp. B13.
The genome of the newly identified bacterium Enterobacter sp. B13 encodes for a b class carbonic anhydrases (CAs, EC 4.2.1.1) EspCA. This enzyme was recently cloned, and characterized kinetically by this group (J. Enzyme Inhib. Med. Chem. 2016, 31) Here we report an inhibition study with sulfonamides and sulfamates of this enzyme. The best EspCA inhibitors were some sulfanylated sulfonamides with elongated molecules, metanilamide, 4 aminoalkyl benzenesulfonamides, acetazolamide, and deacetylated methazolamide (KIs in the range of 58.7 96.5nM) Clinically used agents such as methazolamide, ethoxzolamide, dorzolamide, brinzolamide, benzolamide, zonisamide, sulthiame, sulpiride, topiramate and valdecoxib were slightly less effective inhibitors (KIs in the range of 103 138nM) Saccharin, celecoxib, dichlorophenamide and many simple benzenesulfonamides were even less effective as EspCA inhibitors, with KIs in the range of 384 938nM. Identification of effective inhibitors of this bacterial enzyme may lead to pharmacological tools useful for understanding the physiological role(s) of the b class CAs in bacterial pathogenicity/virulence.
Bioorganic medicinal chemistry letters