title: Synthesis and inhibition potency of novel ureido benzenesulfonamides incorporating GABA as tumor-associated carbonic anhydrase IX and XII inhibitors.
abstract: New ureido benzenesulfonamides incorporating a GABA moiety as a linker between the ureido and the sulfonamide functionalities were synthesized and their inhibition potency determined against both the predominant cytosolic (hCA I and II) and the transmembrane tumor-associated (hCA IX and XII) isoforms of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1). The majority of these compounds were medium potency inhibitors of the cytosolic isoform hCA I and effective hCA II inhibitors, whereas they showed strong inhibition of the two transmembrane tumor-associated isoforms hCA IX and XII, with KIs in nanomolar range. Only one derivative had a good selectivity for inhibition of the tumor-associated hCA IX target isoform over the cytosolic and physiologically dominant off-target hCA I and II, being thus a potential tool to develop new anticancer agents.
authors: a Dipartimento di Chimica, Laboratorio di Chimica Bioinorganica , Università degli Studi di Firenze , Sesto Fiorentino (Firenze) , Italy and.
authors: Mariangela
authors: M
authors: Ceruso
authors: a Dipartimento di Chimica, Laboratorio di Chimica Bioinorganica , Università degli Studi di Firenze , Sesto Fiorentino (Firenze) , Italy and.
authors: Sabrina
authors: S
authors: Antel
authors: a Dipartimento di Chimica, Laboratorio di Chimica Bioinorganica , Università degli Studi di Firenze , Sesto Fiorentino (Firenze) , Italy and.
authors: Andrea
authors: A
authors: Scozzafava
authors: b Neurofarba Department , Università degli Studi di Firenze , Sesto Fiorentino (Florence) , Italy.
authors: Claudiu T
authors: CT
authors: Supuran
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D000071231:Carbonic Anhydrase IX / Q000378:metabolism; D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002256:Carbonic Anhydrases / Q000378:metabolism; D060326:Chemistry Techniques, Synthetic; D003600:Cytosol / Q000187:drug effects / Q000201:enzymology; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D013449:Sulfonamides / Q000737:chemistry*; D014508:Urea / Q000737:chemistry; D005680:gamma-Aminobutyric Acid / Q000737:chemistry*; D000096926:Benzenesulfonamides
chemical_list: D000970:Antineoplastic Agents; D000071231:Carbonic Anhydrase IX; D002257:Carbonic Anhydrase Inhibitors; D002256:Carbonic Anhydrases; D007527:Isoenzymes; D013449:Sulfonamides; D014508:Urea; D005680:gamma-Aminobutyric Acid; D000096926:Benzenesulfonamides; C477378:carbonic anhydrase XII
keywords: Anticancer agents; GABA linker; carbonic anhydrase inhibitors; transmembrane isoforms; ureido benzenesulfonamide