title: Inhibition pattern of sulfamide-related compounds in binding to carbonic anhydrase isoforms I, II, VII, XII and XIV.
abstract: A set of sulfamides and sulfamates were synthesized and tested against several isoforms of carbonic anhydrase: CA I, CA II, CA VII, CA XII and CA XIV. The biological assays showed a broad range of inhibitory activity, and interesting results were found for several compounds in terms of activity (Ki <1μm) and selectivity: some aromatic sulfamides are active against CA I, CA II and/or CA VII; while they are less active in CA XII and CA XIV. On the other hand, bulky sulfamides are selective to CA VII. To understand the origin of the different inhibitory activity against each isozyme we used molecular modeling techniques such as docking and molecular dynamic simulations.
authors.affiliation: Medicinal Chemistry, Department of Biological Sciences, Faculty of Exact Sciences, National University of La Plata, 47 and 115, La Plata B1900BJW, Argentina. lgavernet@biol.unlp.edu.ar
authors.forename: Luciana
authors.initials: L
authors.lastname: Gavernet
authors.forename: José L
authors.initials: JL
authors.lastname: Gonzalez Funes
authors.forename: Pablo H
authors.initials: PH
authors.lastname: Palestro
authors.forename: Luis E
authors.initials: LE
authors.lastname: Bruno Blanch
authors.forename: Guillermina L
authors.initials: GL
authors.lastname: Estiu
authors.forename: Alfonso
authors.initials: A
authors.lastname: Maresca
authors.forename: Ivana
authors.initials: I
authors.lastname: Barrios
authors.forename: Claudiu T
authors.initials: CT
authors.lastname: Supuran
mesh_terms: D001665:Binding Sites; D024401:Carbonic Anhydrase I / Q000037:antagonists & inhibitors / Q000378:metabolism; D024402:Carbonic Anhydrase II / Q000037:antagonists & inhibitors / Q000378:metabolism; D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D002256:Carbonic Anhydrases / Q000737:chemistry* / Q000378:metabolism; D020134:Catalytic Domain; D006801:Humans; D062105:Molecular Docking Simulation; D011485:Protein Binding; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D013449:Sulfonamides; D024401:Carbonic Anhydrase I; D024402:Carbonic Anhydrase II; D002256:Carbonic Anhydrases; C477051:carbonic anhydrase VI; C477378:carbonic anhydrase XII; C466621:carbonic anhydrase XIV