Dihalogenated sulfanilamides and benzolamides are effective inhibitors of the three β-class carbonic anhydrases from Mycobacterium tuberculosis.
A series of halogenated sulfanilamides and halogenated benzolamide derivatives have been investigated as inhibitors of three β-carbonic anhydrases (CAs, EC 4.2.1.1) from the bacterial pathogen Mycobacterium tuberculosis, mtCA 1 (Rv1284), mtCA 2 (Rv3588c) and mtCA 3 (Rv3273). All three enzymes were inhibited with efficacies between the submicromolar to the micromolar one, depending on the substitution pattern at the sulfanilamide moiety/fragment of the molecule. Best inhibitors were the halogenated benzolamides (K(I)s in the range of 0.12-0.45 μM) whereas the halogenated sulfanilamides were slightly less inhibitory (K(I)s in the range of 0.41-4.74 μM). This class of β-CA inhibitors may have the potential for developing antimycobacterial agents with a diverse mechanism of action compared to the clinically used drugs for which many strains exhibit multi-drug/extensive multi-drug resistance.
Università degli Studi di Firenze, Polo Scientifico, Laboratorio di Chimica Bioinorganica, Sesto Fiorentino, Florence, Italy.
Alfonso
A
Maresca
Andrea
A
Scozzafava
Daniela
D
Vullo
Claudiu T
CT
Supuran
D001574:Benzolamide / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002256:Carbonic Anhydrases / Q000302:isolation & purification / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000201:enzymology*; D020033:Protein Isoforms / Q000037:antagonists & inhibitors / Q000302:isolation & purification / Q000378:metabolism; D013329:Structure-Activity Relationship; D013424:Sulfanilamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
D002257:Carbonic Anhydrase Inhibitors; D020033:Protein Isoforms; D013424:Sulfanilamides; D002256:Carbonic Anhydrases; D001574:Benzolamide