title: Sulfonamide inhibition studies of the β-carbonic anhydrase from the newly discovered bacterium Enterobacter sp. B13.
abstract: The genome of the newly identified bacterium Enterobacter sp. B13 encodes for a β-class carbonic anhydrases (CAs, EC 4.2.1.1), EspCA. This enzyme was recently cloned, and characterized kinetically by this group (J. Enzyme Inhib. Med. Chem. 2016, 31). Here we report an inhibition study with sulfonamides and sulfamates of this enzyme. The best EspCA inhibitors were some sulfanylated sulfonamides with elongated molecules, metanilamide, 4-aminoalkyl-benzenesulfonamides, acetazolamide, and deacetylated methazolamide (KIs in the range of 58.7-96.5nM). Clinically used agents such as methazolamide, ethoxzolamide, dorzolamide, brinzolamide, benzolamide, zonisamide, sulthiame, sulpiride, topiramate and valdecoxib were slightly less effective inhibitors (KIs in the range of 103-138nM). Saccharin, celecoxib, dichlorophenamide and many simple benzenesulfonamides were even less effective as EspCA inhibitors, with KIs in the range of 384-938nM. Identification of effective inhibitors of this bacterial enzyme may lead to pharmacological tools useful for understanding the physiological role(s) of the β-class CAs in bacterial pathogenicity/virulence.
authors.affiliation: Recep Tayyip Erdogan University, Faculty of Art and Science, Department of Biology, Molecular Biology Research Laboratories, Rize, Turkey.
authors.forename: Ayşenur
authors.initials: A
authors.lastname: Eminoğlu
authors.affiliation: Università degli Studi di Firenze, Dipaertimento di Chimica, Via della Lastruccia 3, 50019 Sesto Fiorentino (Firenze), Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Vullo
authors.affiliation: Selcuk University, Faculty of Medicine, Medical Biology Department, Konya, Turkey.
authors.forename: Aycan
authors.initials: A
authors.lastname: Aşık
authors.affiliation: Giresun University, Bulancak School of Applied Sciences, Giresun, Turkey.
authors.forename: Dilşat Nigar
authors.initials: DN
authors.lastname: Çolak
authors.affiliation: Karadeniz Technical University, Faculty of Science, Department of Biology, Trabzon, Turkey.
authors.forename: Sabriye
authors.initials: S
authors.lastname: Çanakçı
authors.affiliation: Karadeniz Technical University, Faculty of Science, Department of Biology, Trabzon, Turkey. Electronic address: belduz@ktu.edu.tr.
authors.forename: Ali Osman
authors.initials: AO
authors.lastname: Beldüz
authors.affiliation: Università degli Studi di Firenze, Dipaertimento di Chimica, Via della Lastruccia 3, 50019 Sesto Fiorentino (Firenze), Italy; 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.forename: Claudiu T
authors.initials: CT
authors.lastname: Supuran
mesh_terms: D000086:Acetazolamide / Q000737:chemistry / Q000494:pharmacology; D024401:Carbonic Anhydrase I / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002257:Carbonic Anhydrase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D004754:Enterobacter / Q000187:drug effects / Q000201:enzymology*; D004756:Enterobacteriaceae Infections / Q000188:drug therapy* / Q000382:microbiology; D006801:Humans; D008704:Methazolamide / Q000031:analogs & derivatives / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry* / Q000494:pharmacology*; D000096926:Benzenesulfonamides
chemical_list: D000086:Acetazolamide; D024401:Carbonic Anhydrase I; D002257:Carbonic Anhydrase Inhibitors; D008704:Methazolamide; D013449:Sulfonamides; D000096926:Benzenesulfonamides
keywords: Carbonic anhydrase; Enterobacter spp. B13; Inhibitors; Metalloenzymes; Pathogenic bacteria; Sulfonamide