Sulfonamides incorporating fluorine and 1,3,5-triazine moieties are effective inhibitors of three β-class carbonic anhydrases from Mycobacterium tuberculosis

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 beta-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 K-I 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 beta-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.