Inhibition studies of bacterial, fungal and protozoan β-class carbonic anhydrases with Schiff bases incorporating sulfonamide moieties.
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.
['Ceruso|Mariangela|M|', 'Carta|Fabrizio|F|', 'Osman|Sameh M|SM|', 'Alothman|Zeid|Z|', 'Monti|Simona Maria|SM|', 'Supuran|Claudiu T|CT|']
D000900:Anti-Bacterial Agents D000935:Antifungal Agents D000981:Antiprotozoal Agents D001426:Bacterial Proteins D041021:Brucella suis D024401:Carbonic Anhydrase I D024402:Carbonic Anhydrase II D002257:Carbonic Anhydrase Inhibitors D002256:Carbonic Anhydrases D003455:Cryptococcus neoformans D004353:Drug Evaluation, Preclinical D005656:Fungal Proteins D006801:Humans D018314:Leishmania infantum D015800:Protozoan Proteins D012545:Schiff Bases D000077145:Sulfanilamide D013424:Sulfanilamides
Schiff base Sulfonamide Anti-infective Bacteria Beta-carbonic anhydrase Fungi Pathogenic microorganism Protozoa Selective inhibitor