title: Sulfonamide inhibition studies of the γ-carbonic anhydrase from the oral pathogen Porphyromonas gingivalis.
abstract: 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.
authors: Università degli Studi di Firenze, Laboratorio di Chimica Bioinorganica, Rm. 188, Via della Lastruccia 3, I-50019 Sesto Fiorentino (Firenze), Italy.
authors: Daniela
authors: D
authors: Vullo
authors: Istituto di Biochimica delle Proteine and Institute of Bioscience and Bioresources (IBBR), CNR, Via P. Castellino 111, 80131 Napoli, Italy.
authors: Sonia
authors: S
authors: Del Prete
authors: Department of Chemistry, College of Science, King Saud University, PO Box 2455, Riyadh 11451, Saudi Arabia.
authors: Sameh M
authors: SM
authors: Osman
authors: Istituto di Biochimica delle Proteine and Institute of Bioscience and Bioresources (IBBR), CNR, Via P. Castellino 111, 80131 Napoli, Italy.
authors: Viviana
authors: V
authors: De Luca
authors: Università degli Studi di Firenze, Laboratorio di Chimica Bioinorganica, Rm. 188, Via della Lastruccia 3, I-50019 Sesto Fiorentino (Firenze), Italy.
authors: Andrea
authors: A
authors: Scozzafava
authors: Department of Chemistry, College of Science, King Saud University, PO Box 2455, Riyadh 11451, Saudi Arabia.
authors: Zeid
authors: Z
authors: Alothman
authors: Università degli Studi di Firenze, Laboratorio di Chimica Bioinorganica, Rm. 188, Via della Lastruccia 3, I-50019 Sesto Fiorentino (Firenze), Italy; Department of Chemistry, College of Science, King Saud University, PO Box 2455, Riyadh 11451, Saudi Arabia; Università degli Studi di Firenze, Polo Scientifico, Dipartimento NEIROFABA, Sezione di Scienze Farmaceutiche e Nutraceutiche, Via Ugo Schiff 6, 50019 Sesto Fiorentino (Firenze), Italy. Electronic address: claudiu.supuran@unifi.it.
authors: Claudiu T
authors: CT
authors: Supuran
authors: Istituto di Biochimica delle Proteine and Institute of Bioscience and Bioresources (IBBR), CNR, Via P. Castellino 111, 80131 Napoli, Italy. Electronic address: c.capasso@ibp.cnr.it.
authors: Clemente
authors: C
authors: Capasso
mesh_terms: D002257:Carbonic Anhydrase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D002256:Carbonic Anhydrases / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015394:Molecular Structure; D016966:Porphyromonas gingivalis / Q000201:enzymology*; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D013449:Sulfonamides; D002256:Carbonic Anhydrases
keywords: Carbonic anhydrase; Gamma-class enzyme; Porphyromonas gingivalis; Sulfonamide