title: Cyclic tertiary sulfamates: selective inhibition of the tumor-associated carbonic anhydrases IX and XII by N- and O-substituted acesulfame derivatives.
abstract: Carbonic anhydrase (hCA) IX and XII isoforms are over-expressed both in primary and in metastatic cell lines of hypoxic tumors and are innovative targets for cancer diagnosis and treatment. On the basis of the importance of the pharmacophoric sulfamate moiety (bioisostere of the sulfonamide group) present in the structure of recent human CA inhibitors, we designed N-alkylated and O-alkylated derivatives of acesulfame, a cyclic tertiary sulfamate, assessing the inhibitory activity against the ubiquitous isoforms hCA I and II and the cancer-related isoforms hCA IX and XII. All derivatives were nanomolar inhibitors, with some of them possessing an outstanding selectivity towards the tumor-associated hCA IX and/or hCA XII isoforms.
authors.affiliation: Sapienza University of Rome, Department of Drug Chemistry and Technologies, 00185 Roma, Italy. Electronic address: celeste.demonte@uniroma1.it.
authors.forename: Celeste
authors.initials: C
authors.lastname: De Monte
authors.affiliation: Sapienza University of Rome, Department of Drug Chemistry and Technologies, 00185 Roma, Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Carradori
authors.affiliation: Sapienza University of Rome, Department of Drug Chemistry and Technologies, 00185 Roma, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Secci
authors.affiliation: Sapienza University of Rome, Department of Drug Chemistry and Technologies, 00185 Roma, Italy.
authors.forename: Melissa
authors.initials: M
authors.lastname: D'Ascenzio
authors.affiliation: Università degli Studi di Firenze, Polo Scientifico, Laboratorio di Chimica Bioinorganica, 50019 Florence, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Vullo
authors.affiliation: Università degli Studi di Firenze, Polo Scientifico, Laboratorio di Chimica Bioinorganica, 50019 Florence, Italy.
authors.forename: Mariangela
authors.initials: M
authors.lastname: Ceruso
authors.affiliation: Università degli Studi di Firenze, Polo Scientifico, Laboratorio di Chimica Bioinorganica, 50019 Florence, Italy; Università degli Studi di Firenze, Neurofarba Department, Section of Pharmaceutical and Nutraceutical Sciences, Sesto Fiorentino, 50019 Florence, Italy. Electronic address: claudiu.supuran@unifi.it.
authors.forename: Claudiu T
authors.initials: CT
authors.lastname: Supuran
mesh_terms: D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002256:Carbonic Anhydrases / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015394:Molecular Structure; D020033:Protein Isoforms / Q000037:antagonists & inhibitors / Q000378:metabolism; D013329:Structure-Activity Relationship; D013451:Sulfonic Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013843:Thiazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D020033:Protein Isoforms; D013451:Sulfonic Acids; D013843:Thiazines; C005741:sulfamic acid; D002256:Carbonic Anhydrases; C006362:acetosulfame
keywords: Acesulfame derivatives; Anticancer agents; N-alkylation; O-alkylation; Selective hCA IX/hCAXII inhibitors; Sulfamate