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Bioorg Med Chem. 2015 Aug 1;23(15):4181-7. doi: 10.1016/j.bmc.2015.06.050. Epub 2015 Jun 26.

Inhibition studies of bacterial, fungal and protozoan β-class carbonic anhydrases with Schiff bases incorporating sulfonamide moieties.

Author information

1
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.
2
Università degli Studi di Firenze, Polo Scientifico, Laboratorio di Chimica Bioinorganica, Via della Lastruccia 3, 50019 Sesto Fiorentino (Florence), Italy.
3
Department of Chemistry, College of Science, King Saud University, Riyadh 11451, Saudi Arabia.
4
Istituto di Biostrutture e Bioimmagini-CNR, Via Mezzocannone 16, 80134 Napoli, Italy.
5
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.

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.

KEYWORDS:

Anti-infective; Bacteria; Beta-carbonic anhydrase; Fungi; Pathogenic microorganism; Protozoa; Schiff base; Selective inhibitor; Sulfonamide

PMID:
26145821
DOI:
10.1016/j.bmc.2015.06.050
[Indexed for MEDLINE]

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