title: Sulfonamides incorporating heteropolycyclic scaffolds show potent inhibitory action against carbonic anhydrase isoforms I, II, IX and XII.
abstract: Three series of polycyclic compounds possessing either primary sulfonamide or carboxylic acid moieties as zinc-binding groups were investigated as inhibitors of four physiologically relevant CA isoforms, the cytosolic hCA I and II, as well as the transmembrane hCA IX and XII. Most of the new sulfonamides reported here showed excellent inhibitory effects against isoforms hCA II, IX and XII, but no highly isoform-selective inhibition profiles. On the other hand, the carboxylates selectively inhibited hCA IX (KIs ranging between 40.8 and 92.7nM) without inhibiting significantly the other isoforms. Sulfonamides/carboxylates incorporating polycyclic ring systems such as benzothiopyranopyrimidine, pyridothiopyranopyrimidine or dihydrobenzothiopyrano[4,3-c]pyrazole may be considered as interesting candidates for exploring the design of isoform-selective CAIs with various pharmacologic applications.
authors.affiliation: Università di Pisa, Dipartimento di Farmacia, Via Bonanno 6, 56126 Pisa, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Barresi
authors.affiliation: Università di Pisa, Dipartimento di Farmacia, Via Bonanno 6, 56126 Pisa, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Salerno
authors.affiliation: Università di Pisa, Dipartimento di Farmacia, Via Bonanno 6, 56126 Pisa, Italy. Electronic address: marini@unipi.it.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Marini
authors.affiliation: Università di Pisa, Dipartimento di Farmacia, Via Bonanno 6, 56126 Pisa, Italy.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Taliani
authors.affiliation: Università di Pisa, Dipartimento di Farmacia, Via Bonanno 6, 56126 Pisa, Italy.
authors.forename: Concettina
authors.initials: C
authors.lastname: La Motta
authors.affiliation: Università di Pisa, Dipartimento di Farmacia, Via Bonanno 6, 56126 Pisa, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Simorini
authors.affiliation: Università di Pisa, Dipartimento di Farmacia, Via Bonanno 6, 56126 Pisa, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Da Settimo
authors.affiliation: Università degli Studi di Firenze, Polo Scientifico, Laboratorio di Chimica Bioinorganica, Rm. 188, Via della Lastruccia 3, 50019 Sesto Fiorentino (Florence), Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Vullo
authors.affiliation: Università degli Studi di Firenze, NEUROFARBA Department, Sezione di Scienze Farmaceutiche e Nutraceutiche, Via Ugo Schiff 6, 50019 Sesto Fiorentino (Florence), Italy. Electronic address: claudiu.supuran@unifi.it.
authors.forename: Claudiu T
authors.initials: CT
authors.lastname: Supuran
mesh_terms: D024401:Carbonic Anhydrase I / Q000737:chemistry*; D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D002264:Carboxylic Acids / Q000737:chemistry*; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000737:chemistry; D007700:Kinetics; D011485:Protein Binding; D011720:Pyrazoles / Q000737:chemistry*; D011743:Pyrimidines / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D002264:Carboxylic Acids; D007527:Isoenzymes; D011720:Pyrazoles; D011743:Pyrimidines; D013449:Sulfonamides; D024401:Carbonic Anhydrase I
keywords: Benzothiopyranopyrimidine; Carbonic anhydrase; Carboxylic acid; Dihydrbenzothiopyrano[4,3-c]pyrazole; Pyridothiopyranopyrimidine; Sulfonamide