title: 4-Arylbenzenesulfonamides as Human Carbonic Anhydrase Inhibitors (hCAIs): Synthesis by Pd Nanocatalyst-Mediated Suzuki-Miyaura Reaction, Enzyme Inhibition, and X-ray Crystallographic Studies.
abstract: Benzenesulfonamides bearing various substituted (hetero)aryl rings in the para-position were prepared by palladium nanoparticle-catalyzed Suzuki-Miyaura cross-coupling reactions and evaluated as human carbonic anhydrase (hCA, EC 4.2.1.1) inhibitors against isoforms hCA I, II, IX, and XII. Most of the prepared sulfonamides showed low inhibition against hCA I isoform, whereas the other cytosolic isoenzyme, hCA II, was strongly affected. The major part of these new derivatives acted as potent inhibitors of the tumor-associated isoform hCA XII. An opposite trend was observed for phenyl, naphthyl, and various heteroaryl substituted benzenesulfonamides which displayed subnanomolar hCA IX inhibition while poorly inhibiting the other tumor-associated isoform hCA XII. The inhibition potency and influence of the partially restricted aryl-aryl bond rotation on the activity/selectivity were rationalized by means of X-ray crystallography of the adducts of hCA II with several 4-arylbenzenesulfonamides.
authors.affiliation: Institut de Chimie Moléculaire de Reims, CNRS UMR 7312, Université de Reims Champagne-Ardenne, UFR Pharmacie, 51 Rue Cognacq-Jay, F-51096 Reims Cedex, France.|Dipartimento di Farmacia, Università "G. d'Annunzio" , Via dei Vestini, I-66100 Chieti, Italy.
authors.forename: Benedetta
authors.initials: B
authors.lastname: Cornelio
authors.affiliation: Institut de Chimie Moléculaire de Reims, CNRS UMR 7312, Université de Reims Champagne-Ardenne, UFR Pharmacie, 51 Rue Cognacq-Jay, F-51096 Reims Cedex, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Laronze-Cochard
authors.affiliation: Dipartimento di Chimica Ugo Schiff, Università degli Studi di Firenze , Via della Lastruccia 3, I-50019 Sesto Fiorentino, Firenze, Italy.
authors.forename: Mariangela
authors.initials: M
authors.lastname: Ceruso
authors.affiliation: Dipartimento di Chimica Ugo Schiff, Università degli Studi di Firenze , Via della Lastruccia 3, I-50019 Sesto Fiorentino, Firenze, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Ferraroni
authors.affiliation: School of Chemistry, University of Nottingham , University Park, Nottingham, NG7 2RD, U.K.
authors.forename: Graham A
authors.initials: GA
authors.lastname: Rance
authors.affiliation: Dipartimento di Chimica Ugo Schiff, Università degli Studi di Firenze , Via della Lastruccia 3, I-50019 Sesto Fiorentino, Firenze, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Carta
authors.affiliation: School of Chemistry, University of Nottingham , University Park, Nottingham, NG7 2RD, U.K.|Nottingham Nanotechnology and Nanoscience Centre, University of Nottingham , University Park, Nottingham, NG7 2RD, U.K.
authors.forename: Andrei N
authors.initials: AN
authors.lastname: Khlobystov
authors.affiliation: Dipartimento di Farmacia, Università "G. d'Annunzio" , Via dei Vestini, I-66100 Chieti, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Fontana
authors.affiliation: Dipartimento di Chimica Ugo Schiff, Università degli Studi di Firenze , Via della Lastruccia 3, I-50019 Sesto Fiorentino, Firenze, Italy.|Neurofarba Dept., Sezione di Scienze Farmaceutiche e Nutraceutiche, Università degli Studi di Firenze , Via U. Schiff 6, I-50019 Sesto Fiorentino, Firenze, Italy.
authors.forename: Claudiu T
authors.initials: CT
authors.lastname: Supuran
authors.affiliation: Institut de Chimie Moléculaire de Reims, CNRS UMR 7312, Université de Reims Champagne-Ardenne, UFR Pharmacie, 51 Rue Cognacq-Jay, F-51096 Reims Cedex, France.
authors.forename: Janos
authors.initials: J
authors.lastname: Sapi
mesh_terms: D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D002384:Catalysis; D018360:Crystallography, X-Ray; D015195:Drug Design; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008958:Models, Molecular; D049329:Nanostructures; D009369:Neoplasms / Q000201:enzymology; D010165:Palladium / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000494:pharmacology*
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D007527:Isoenzymes; D013449:Sulfonamides; D010165:Palladium