title: Anion inhibition studies of the β-carbonic anhydrase from the pathogenic bacterium Vibrio cholerae.
abstract: The genome of the pathogenic bacterium Vibrio cholerae encodes for three carbonic anhydrases (CAs, EC 4.2.1.1) belonging to the α-, β- and γ-classes. Here we report and anion inhibition study of the β-CA, VchCAβ with anions and other small molecules which inhibit metalloenzymes. The best VchCAβ anion inhibitors were sulfamide, sulfamate, phenylboronic acid and phenylarsonic acid, which showed KIs in the range of 54-86μM. Diethyldithiocarbonate was also an effective VchCAβ inhibitor, with an inhibition constant of 0.73mM. The halides, cyanate, thiocyanate, cyanide, bicarbonate, carbonate, nitrate, nitrite, stannate, selenate, tellurate, divanadate, tetraborate, perrhenate, perruthenate, peroxydisulfate, selenocyanide, trithiocarbonate, and fluorosulfonate showed affinity in the low millimolar range, with KIs of 2.3-9.5mM. Identification of selective inhibitors of VchCAβ (over the human CA isoforms) may lead to pharmacological tools useful for understanding the physiological role(s) of this under-investigated enzyme.
authors: Università degli Studi di Firenze, Dipartimento Di Chimica, Laboratorio di Chimica Bioinorganica, Polo Scientifico, Via della Lastruccia 3, 50019 Sesto Fiorentino, Florence, Italy.
authors: Daniela
authors: D
authors: Vullo
authors: Università degli Studi di Firenze, Dipartimento Di Chimica, Laboratorio di Chimica Bioinorganica, Polo Scientifico, Via della Lastruccia 3, 50019 Sesto Fiorentino, Florence, Italy; Istituto di Bioscienze e Biorisorse, CNR, Via Pietro Castellino 81, Napoli, Italy.
authors: Sonia
authors: S
authors: Del Prete
authors: Istituto di Bioscienze e Biorisorse, CNR, Via Pietro Castellino 81, Napoli, Italy.
authors: Viviana
authors: V
authors: De Luca
authors: Istituto di Bioscienze e Biorisorse, CNR, Via Pietro Castellino 81, Napoli, Italy.
authors: Vincenzo
authors: V
authors: Carginale
authors: Università degli Studi di Firenze, Dipartimento Di Chimica, Laboratorio di Chimica Bioinorganica, Polo Scientifico, Via della Lastruccia 3, 50019 Sesto Fiorentino, Florence, Italy.
authors: Marta
authors: M
authors: Ferraroni
authors: Università degli Studi di Firenze, Dipartimento Di Chimica, Laboratorio di Chimica Bioinorganica, Polo Scientifico, Via della Lastruccia 3, 50019 Sesto Fiorentino, Florence, Italy.
authors: Nurcan
authors: N
authors: Dedeoglu
authors: King Saud University, Department of Chemistry, Riyadh, Saudi Arabia.
authors: Sameh M
authors: SM
authors: Osman
authors: King Saud University, Department of Chemistry, Riyadh, Saudi Arabia.
authors: Zeid
authors: Z
authors: AlOthman
authors: Istituto di Bioscienze e Biorisorse, CNR, Via Pietro Castellino 81, Napoli, Italy. Electronic address: clemente.capasso@ibbr.cnr.it.
authors: Clemente
authors: C
authors: Capasso
authors: King Saud University, Department of Chemistry, Riyadh, Saudi Arabia; Università degli Studi di Firenze, Dipartimento Neurofarba, Sezione di Scienze Farmaceutiche e Nutraceutiche, Via U. Schiff 6, 50019 Sesto Fiorentino, Florence, Italy. Electronic address: claudiu.supuran@unifi.it.
authors: Claudiu T
authors: CT
authors: Supuran
mesh_terms: D000838:Anions / Q000737:chemistry / Q000494:pharmacology; D001152:Arsenicals / Q000737:chemistry / Q000494:pharmacology; D001897:Boronic Acids / Q000737:chemistry / Q000494:pharmacology; D002257:Carbonic Anhydrase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D002256:Carbonic Anhydrases / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D008958:Models, Molecular; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry / Q000494:pharmacology; D013451:Sulfonic Acids / Q000737:chemistry / Q000494:pharmacology; D014734:Vibrio cholerae / Q000201:enzymology*
chemical_list: D000838:Anions; D001152:Arsenicals; D001897:Boronic Acids; D002257:Carbonic Anhydrase Inhibitors; D013449:Sulfonamides; D013451:Sulfonic Acids; C005741:sulfamic acid; D002256:Carbonic Anhydrases; C010686:benzeneboronic acid
keywords: Anions; Carbonic anhydrase; Hydratase activity; Inhibitors; Metalloenzymes; Pathogenic bacteria; Vibrio cholerae