Sulfonamide inhibition studies of the 纬-carbonic anhydrase from the oral pathogen Porphyromonas gingivalis
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- 作者：Daniela Vullo ; Sonia Del Prete ; Sameh M. Osman ; Viviana De Luca ; Andrea Scozzafava ; Zeid AlOthman ; Claudiu T. Supuran ; Clemente Capasso
- 关键词：Carbonic anhydrase ; Gamma-class enzyme ; Sulfonamide ; Porphyromonas gingivalis
- 刊名：Bioorganic and Medicinal Chemistry Letters
- 出版年：1 January, 2014
- 年：2014
- 卷：24
- 期：1
- 页码：240-244
- 全文大小：434 K
文摘
A carbonic anhydrase (CA, EC 4.2.1.1) denominated PgiCA, belonging to the 纬-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 131-380 nM). The inhibition profile of PgiCA was very different from that of CAM, hCA I and II or the 尾-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.