title: New series of sulfonamides containing amino acid moiety act as effective and selective inhibitors of tumor-associated carbonic anhydrase XII.
abstract: New benzenesulfonamides incorporating water solubilizing moieties were synthesized using N-α-acetyl-l-lysine or γ-aminobutyric acid as scaffolds followed by the conversion of their terminal amino group to the guanidine one. Their inhibition activity was assessed by determining their KIs values against the human (h) carbonic anhydrase (CA, EC 4.2.1.1) isoforms hCA I, II, IX and XII. Some of these compounds were medium potency inhibitors of the cytosolic (CA I, II) and transmembrane (CA IX) isoforms and highly effective, nanomolar inhibitors of the second transmembrane isoform hCA XII. Some of these sulfonamides possessing good selectivity inhibition for the tumor-associated CA XII isoform over the cytosolic and physiologically dominant isoforms CA I and II may be used as tools to develop new anticancer agents.
authors.affiliation: Dipartimento di Chimica, Laboratorio di Chimica Bioinorganica .
authors.forename: Mariangela
authors.initials: M
authors.lastname: Ceruso
authors.forename: Marco
authors.initials: M
authors.lastname: Bragagni
authors.forename: Zeid
authors.initials: Z
authors.lastname: AlOthman
authors.forename: Sameh M
authors.initials: SM
authors.lastname: Osman
authors.forename: Claudiu T
authors.initials: CT
authors.lastname: Supuran
mesh_terms: D000596:Amino Acids / Q000737:chemistry*; 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; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000596:Amino Acids; D002257:Carbonic Anhydrase Inhibitors; D013449:Sulfonamides; D002256:Carbonic Anhydrases; C477378:carbonic anhydrase XII
keywords: Amino acid; carbonic anhydrase inhibitor; sulfonamide; tumor-associated CA XII