title: Carbonic anhydrase and matrix metalloproteinase inhibitors. Inhibition of human tumor-associated isozymes IX and cytosolic isozyme I and II with sulfonylated hydroxamates.
abstract: A series of sulfonylated hydroxamates were synthesized and evaluated as dual inhibitors of both human carbonic anhydrases (hCAs) and matrix metalloproteinases (MMPs), two metalloenzyme families involved in carcinogenesis and tumor invasion processes. The new derivatives were tested on three CA isozymes, the cytosolic isozymes I and II, and the transmembrane, tumor-associated isozyme IX, and also on human gelatinases (MMP-2 and MMP-9). Some of the new derivatives proved to be potent and selective inhibitors of CA II, but only compounds 3b and 6b, devoid of the arylsulfonyl moiety, proved to have a better inhibitory activity on hCA IX than on hCA I and II, in the micromolar range.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università di Pisa, via Bonanno 6, 56126 Pisa, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Nuti
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Orlandini
authors.forename: Susanna
authors.initials: S
authors.lastname: Nencetti
authors.forename: Armando
authors.initials: A
authors.lastname: Rossello
authors.forename: Alessio
authors.initials: A
authors.lastname: Innocenti
authors.forename: Andrea
authors.initials: A
authors.lastname: Scozzafava
authors.forename: Claudiu T
authors.initials: CT
authors.lastname: Supuran
mesh_terms: D000818:Animals; D024401:Carbonic Anhydrase I / Q000037:antagonists & inhibitors*; D024402:Carbonic Anhydrase II / Q000037:antagonists & inhibitors*; D003600:Cytosol / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D006877:Hydroxamic Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D007527:Isoenzymes; D061965:Matrix Metalloproteinase Inhibitors; D051379:Mice; D015394:Molecular Structure; D009101:Multiple Myeloma / Q000188:drug therapy / Q000473:pathology; D013329:Structure-Activity Relationship; D013451:Sulfonic Acids / Q000737:chemistry*; D014407:Tumor Cells, Cultured
chemical_list: D004791:Enzyme Inhibitors; D006877:Hydroxamic Acids; D007527:Isoenzymes; D061965:Matrix Metalloproteinase Inhibitors; D013451:Sulfonic Acids; D024401:Carbonic Anhydrase I; D024402:Carbonic Anhydrase II