title: Inhibition studies of bacterial, fungal and protozoan β-class carbonic anhydrases with Schiff bases incorporating sulfonamide moieties.
abstract: A series of new Schiff bases derived from sulfanilamide, 3-fluorosulfanilamide or 4-(2-aminoethyl)-benzenesulfonamide containing either a hydrophobic or a hydrophilic tail, have been investigated as inhibitors of three β-carbonic anhydrases (CA, EC 4.2.1.1) from three different microorganisms. Their antifungal, antibacterial and antiprotozoan activities have been determined against the pathogenic fungus Cryptococcus neoformans, the bacterial pathogen Brucella suis and the protozoan parasite Leishmania donovani chagasi, responsible for Leishmaniasis. The results of these inhibition studies show that all three enzymes were efficiently inhibited by the Schiff base sulfonamides with KI values in the nanomolar or submicromolar range, depending on the nature of the tail, coming from the aryl/heteroaryl moiety present in the starting aldehyde employed in the synthesis. Furthermore, the compounds hereby investigated revealed high β-CAs selectivity over the ubiquitous, physiologically relevant and off-target human isoforms (CA I and II) and to be more potent as antifungal and antibacterial than as antiprotozoan potential drugs.
authors.affiliation: Università degli Studi di Firenze, Polo Scientifico, Laboratorio di Chimica Bioinorganica, Via della Lastruccia 3, 50019 Sesto Fiorentino (Florence), Italy. Electronic address: mariangela.ceruso@unifi.it.
authors.forename: Mariangela
authors.initials: M
authors.lastname: Ceruso
authors.affiliation: Università degli Studi di Firenze, Polo Scientifico, Laboratorio di Chimica Bioinorganica, Via della Lastruccia 3, 50019 Sesto Fiorentino (Florence), Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Carta
authors.affiliation: Department of Chemistry, College of Science, King Saud University, Riyadh 11451, Saudi Arabia.
authors.forename: Sameh M
authors.initials: SM
authors.lastname: Osman
authors.affiliation: Department of Chemistry, College of Science, King Saud University, Riyadh 11451, Saudi Arabia.
authors.forename: Zeid
authors.initials: Z
authors.lastname: Alothman
authors.affiliation: Istituto di Biostrutture e Bioimmagini-CNR, Via Mezzocannone 16, 80134 Napoli, Italy.
authors.forename: Simona Maria
authors.initials: SM
authors.lastname: Monti
authors.affiliation: Università degli Studi di Firenze, Polo Scientifico, Laboratorio di Chimica Bioinorganica, Via della Lastruccia 3, 50019 Sesto Fiorentino (Florence), Italy; Università degli Studi di Firenze, Dipartimento NEUROFARBA, Sezione di Scienze Farmaceutiche, Via Ugo 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: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D000935:Antifungal Agents / Q000737:chemistry / Q000494:pharmacology*; D000981:Antiprotozoal Agents / Q000737:chemistry / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D041021:Brucella suis / Q000187:drug effects; D024401:Carbonic Anhydrase I / Q000378:metabolism; D024402:Carbonic Anhydrase II / Q000378:metabolism; D002257:Carbonic Anhydrase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D002256:Carbonic Anhydrases / Q000378:metabolism; D003455:Cryptococcus neoformans / Q000187:drug effects; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005656:Fungal Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D018314:Leishmania infantum / Q000187:drug effects; D015800:Protozoan Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D012545:Schiff Bases; D000077145:Sulfanilamide; D013424:Sulfanilamides / Q000737:chemistry
chemical_list: D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D000981:Antiprotozoal Agents; D001426:Bacterial Proteins; D002257:Carbonic Anhydrase Inhibitors; D005656:Fungal Proteins; D015800:Protozoan Proteins; D012545:Schiff Bases; D013424:Sulfanilamides; D000077145:Sulfanilamide; D024401:Carbonic Anhydrase I; D024402:Carbonic Anhydrase II; D002256:Carbonic Anhydrases
keywords: Anti-infective; Bacteria; Beta-carbonic anhydrase; Fungi; Pathogenic microorganism; Protozoa; Schiff base; Selective inhibitor; Sulfonamide