Inhibition studies of Brucella suis β-carbonic anhydrases with a series of 4-substituted pyridine-3-sulphonamides. (1st January 2018)

• Record Type: Journal Article
• Authors: Monti, Simona Maria; Meccariello, Angela; Ceruso, Mariangela; Szafrański, Krzysztof; Sławiński, Jarosław; Supuran, Claudiu T.
• Is Part Of: Journal of enzyme inhibition and medicinal chemistry. Volume 33:Number 1(2018)
• Page Start: 255
• Page End: 259
• Publication Date: 2018-01-01
• Subjects: Carbonic anhydrase -- Brucella suis -- sulphonamide -- heterocycle -- antibacterials; Enzyme inhibitors -- Periodicals; Enzyme Inhibitors -- periodicals; Biochemistry -- periodicals; 572.7
• DOI: 10.1080/14756366.2017.1413097
• Languages: English
• ISSNs: 1475-6366

Abstract

Abstract: The two β-carbonic anhydrases (CAs, EC 4.2.1.1) from the pathogenic bacterium Brucella suis, BsuCA1 and BsuCA2, were investigated for their inhibition profile with a series of pyridine-3-sulphonamide derivatives incorporating 4-hetaryl moieties. BsuCA1 was effectively inhibited by these sulphonamides with inhibition constants ranging between 34 and 624 nM. BsuCA2 was less sensitive to these inhibitors, with KI s in the range of 62 nM - > 10 µM. The nature of the 4-substituent present on the pyridine ring was the main factor influencing the inhibitory profile against both isoforms, with 4-halogenophenylpiperazin-1-yl and 3, 4, 5-trisubstituted-pyrazol-1-yl derivatives showing the most effective inhibition. Some of these sulphonamides were most effective bacterial CA than human (h) CA I and II inhibitors, making them selective for the prokaryotic enzymes. Investigation of bacterial CA inhibitors may be relevant for finding antibiotics with a new mechanism of action compared to the clinically used agents for which substantial drug resistance emerged.