title: Dithiocarbamates strongly inhibit the β-class carbonic anhydrases from Mycobacterium tuberculosis.
abstract: A series of N-mono- and N,N-disubstituted dithiocarbamates have been investigated as inhibitors of two β-carbonic anhydrases (CAs, EC 4.2.1.1) from the bacterial pathogen Mycobacterium tuberculosis, mtCA 1 (Rv1284) and mtCA 3 (Rv3273). Both enzymes were inhibited with efficacies between the subnanomolar to the micromolar one, depending on the substitution pattern at the nitrogen atom from the dithiocarbamate zinc-binding group. Aryl, arylalkyl-, heterocyclic as well as aliphatic and amino acyl such moieties led to potent mtCA 1 and 3 inhibitors in both the N-mono- and N,N-disubstituted dithiocarbamate series. This new 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.
authors.affiliation: Università degli Studi di Firenze, Polo Scientifico, Laboratorio di Chimica Bioinorganica, Sesto Fiorentino (Florence), Italy.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Maresca
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Carta
authors.forename: Daniela
authors.initials: D
authors.lastname: Vullo
authors.forename: Claudiu T
authors.initials: CT
authors.lastname: Supuran
mesh_terms: D002245:Carbon Dioxide / Q000737:chemistry / Q000378:metabolism; D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002256:Carbonic Anhydrases / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000201:enzymology*; D020033:Protein Isoforms / Q000037:antagonists & inhibitors / Q000378:metabolism; D013329:Structure-Activity Relationship; D013859:Thiocarbamates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D020033:Protein Isoforms; D013859:Thiocarbamates; D002245:Carbon Dioxide; D002256:Carbonic Anhydrases