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


, : Sulfonamide inhibition studies of the γ-carbonic anhydrase from the oral pathogen Porphyromonas gingivalis. Bioorganic & Medicinal Chemistry Letters 24(1): 240-244

A carbonic anhydrase (CA, EC 4.2.1.1) denominated PgiCA, belonging to the γ-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 (KIs in the range of 131-380nM). The inhibition profile of PgiCA was very different from that of CAM, hCA I and II or the β-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.

US$19.90

PMID: 24316122

DOI: 10.1016/j.bmcl.2013.11.030


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