title: Sulfonamides incorporating fluorine and 1,3,5-triazine moieties are effective inhibitors of three β-class carbonic anhydrases from Mycobacterium tuberculosis.
abstract: A new series of fluorine containing 1,3,5-triazinyl sulfonamide derivatives obtained from cyanuric fluoride, sulfanilamide/4-aminoethylbenzenesulfonamide followed and incorporating also amin0, amino alcohol and amino acid moieties have been investigated as inhibitors of three β-carbonic anhydrases (CAs, EC 4.2.1.1) from the bacterial pathogen Mycobacterium tuberculosis, mtCA1 (Rv1284), mtCA 2 (Rv3588c) and mtCA 3 (Rv3273). All three enzymes were efficiently inhibited by these sulfonamides with KI values in the nanomolar or submicromolar range, depending on the substitution of one or both fluorine atoms at the 1,3,5-triazine ring. As some of these enzymes are crucial for the life cycle of this bacterium, the class of β-CA inhibitors reported in this study may lead to antimycobacterial agents with a different mechanism of action compared to the clinically used such drugs for which the pathogen developed extensive drug resistance.
authors.affiliation: Laboratorio di Chimica Bioinorganica, Polo Scientifico, Università degli Studi di Firenze , Florence , Italy and.
authors.forename: Mariangela
authors.initials: M
authors.lastname: Ceruso
authors.forename: Daniela
authors.initials: D
authors.lastname: Vullo
authors.forename: Andrea
authors.initials: A
authors.lastname: Scozzafava
authors.forename: Claudiu T
authors.initials: CT
authors.lastname: Supuran
mesh_terms: D055162:Biocatalysis; D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002256:Carbonic Anhydrases / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005461:Fluorine / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000201:enzymology*; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry / Q000494:pharmacology*; D014227:Triazines / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D013449:Sulfonamides; D014227:Triazines; D005461:Fluorine; D002256:Carbonic Anhydrases
keywords: 1,3,5-triazine; Mycobacterium tuberculosis; carbonic anhydrase; fluoride; sulfonamide; β-Carbonic anhydrases