Sulfonamide inhibition studies of the gamma-carbonic anhydrase from the oral pathogen Porphyromonas gingivalis

A carbonic anhydrase (CA, EC 4.2.1.1) denominated PgiCA, belonging to the gamma-class, from the oral pathogenic bacteria Porphyromonas gingivalis, the main causative agent of periodontitis, was investigated for its inhibition profile with sulfonamides and one sulfamate. Dichlorophenamide, topiramate and many simple aromatic/ heterocyclic sulfonamides were ineffective as PgiCA inhibitors whereas the best inhibition was observed with halogenosulfanilamides incorporating heavy halogens, 4-hydroxy-and 4-hydroxyalkyl- benzenesulfonamides, acetazolamide, methazolamide, zonisamide, indisulam, celecoxib, saccharin and hydrochlorothiazide (K(I)s in the range of 131-380 nM). The inhibition profile of PgiCA was very different from that of CAM, hCA I and II or the beta-CA from a protozoan parasite (Leishmania donovani chagasii). Identification of potent and possibly selective inhibitors of PgiCA may lead to pharmacological tools useful for understanding the physiological role(s) of this enzyme. (C) 2013 Elsevier Ltd. All rights reserved.