title: Carbonic Anhydrase Inhibition with Benzenesulfonamides and Tetrafluorobenzenesulfonamides Obtained via Click Chemistry.
abstract: A series of novel benzene- and 2,3,5,6-tetrafluorobenzenesulfonamide was synthesized by using a click chemistry approach starting from azido-substituted sulfonamides and alkynes, incorporating aryl, alkyl, cycloalkyl, and amino-/hydroxy-/halogenoalkyl moieties. The new compounds were medium potency inhibitors of the cytosolic carbonic anhydrase (CA, EC 4.2.1.1) isoforms I and II and low nanomolar/subnanomolar inhibitors of the tumor-associated hCA IX and XII isoforms. The X-ray crystal structure of two such sulfonamides in adduct with hCA II allowed us to understand the factors governing inhibitory power.
authors.affiliation: Dipartimento di Chimica e Farmacia, Università di Sassari , Via Vienna 2, 07100 Sassari, Italy.
authors.forename: Nicolino
authors.initials: N
authors.lastname: Pala
authors.affiliation: Dipartimento di Chimica e Farmacia, Università di Sassari , Via Vienna 2, 07100 Sassari, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Micheletto
authors.affiliation: Dipartimento di Chimica e Farmacia, Università di Sassari , Via Vienna 2, 07100 Sassari, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Sechi
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Medicine, University of Florida , Box 100245, Gainesville, Florida 32610, United States.
authors.forename: Mayank
authors.initials: M
authors.lastname: Aggarwal
authors.affiliation: Laboratorio di Chimica Bioinorganica, Università degli Studi di Firenze , Rm 188, Via della Lastruccia 3, 50019 Sesto Fiorentino (Firenze), Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Carta
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Medicine, University of Florida , Box 100245, Gainesville, Florida 32610, United States.
authors.forename: Robert
authors.initials: R
authors.lastname: McKenna
authors.affiliation: Laboratorio di Chimica Bioinorganica, Università degli Studi di Firenze , Rm 188, Via della Lastruccia 3, 50019 Sesto Fiorentino (Firenze), Italy ; Neurofarba Dept., Università degli Studi di Firenze , Via U. Schiff 6, 50019 Sesto Fiorentino (Firenze), Italy.
authors.forename: Claudiu T
authors.initials: CT
authors.lastname: Supuran
keywords: Carbonic anhydrase; benzenesulfonamide; click chemistry; human isoform I; human isoform II; human isoform IX; human isoform XII