title: Sulfonamides incorporating boroxazolidone moieties are potent inhibitors of the transmembrane, tumor-associated carbonic anhydrase isoforms IX and XII.
abstract: A new series of sulfonamides was synthesized by the reaction of the boroxazolidone complex of l-lysine with isothiocyanates incorporating sulfamoyl moieties and diverse organic scaffolds. The obtained thioureas have been investigated as inhibitors of four physiologically relevant human carbonic anhydrase (hCA, EC 4.2.1.1) isoforms, hCA I, II, IX and XII. Inhibition between the low nanomolar to the micromolar range has been observed against them, with several low nanomolar and tumor-CA selective inhibitors detected. These boron-containing compounds might be useful for the management of hypoxic tumors overexpressing hCA IX/XII by means of boron neutron capture therapy, a technique not investigated so far with inhibitors of this enzyme.
authors.affiliation: Institut des Biomolécules Max Mousseron (IBMM), UMR 5247 CNRS-UM1-UM2, Bâtiment de Recherche Max Mousseron, Ecole Nationale Supérieure de Chimie de Montpellier, 8 rue de l'Ecole Normale, 34296 Montpellier Cedex, France.
authors.forename: Marouan
authors.initials: M
authors.lastname: Rami
authors.forename: Alfonso
authors.initials: A
authors.lastname: Maresca
authors.forename: Fatma-Zhora
authors.initials: FZ
authors.lastname: Smaine
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Montero
authors.forename: Andrea
authors.initials: A
authors.lastname: Scozzafava
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Winum
authors.forename: Claudiu T
authors.initials: CT
authors.lastname: Supuran
mesh_terms: D000951:Antigens, Neoplasm / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001896:Boron Compounds / Q000737:chemistry*; D000071231:Carbonic Anhydrase IX; D002257:Carbonic Anhydrase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D002256:Carbonic Anhydrases / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects*; D006801:Humans; D015394:Molecular Structure; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors; D023303:Oxazolidinones / Q000737:chemistry*; D020033:Protein Isoforms; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D001896:Boron Compounds; D002257:Carbonic Anhydrase Inhibitors; D009363:Neoplasm Proteins; D023303:Oxazolidinones; D020033:Protein Isoforms; D013449:Sulfonamides; C060387:boroxazolidone; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases; C477378:carbonic anhydrase XII