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Sulfonamides incorporating boroxazolidone moieties are potent inhibitors of the transmembrane, tumor-associated carbonic anhydrase isoforms IX and XII |
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| Authors: | Rami Marouan Maresca Alfonso Smaine Fatma-Zhora Montero Jean-Louis Scozzafava Andrea Winum Jean-Yves Supuran Claudiu T |
| Affiliation: | a 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 b Università degli Studi di Firenze, Laboratorio di Chimica Bioinorganica, Rm 188, Via della Lastruccia 3, I-50019 Sesto Fiorentino (Firenze), Italy c Université d’Annaba, Faculté des Sciences, Département de Chimie, BP12, 23000 Annaba, Algeria |
| 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. |
| Keywords: | Carbonic anhydrase Isoform I, II, IX, XII Hypoxic tumor Boroxazolidones Sulfonamides Thioureas |
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