title: Sulfamide derivatives with selective carbonic anhydrase VII inhibitory action.
abstract: A set of N,N'-disubstituted sulfamides and sodium cyclamate have been tested for their inhibitory action against six isoforms of carbonic anhydrase (CA, EC 4.2.1.1) found in the brain, that is, CA I, CA II, CA VII, CA IX, CA XII and CA XIV, some of which are involved in epileptogenesis. The biological data showed interesting results for CA VII inhibition, the isozyme thought to be a novel antiepileptic target. Strong CA VII inhibitors, with Ki values in the low nanomolar-subnanomolar range were identified. Some of these derivatives showed selectivity for inhibition of CA VII versus the ubiquitous isoform CA II, for which the Ki values were in the micromolar range. Molecular modeling approaches were employed to understand the binding interactions between these compounds and the two CA isoforms, since the mechanism of action of such disubstituted sulfamides was not yet investigated by means of X-ray crystallography.
authors.affiliation: Medicinal Chemistry, Department of Biological Sciences, Faculty of Exact Sciences, National University of La Plata, 47 and 115, La Plata B1900BJW, Argentina.
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Villalba
authors.affiliation: Medicinal Chemistry, Department of Biological Sciences, Faculty of Exact Sciences, National University of La Plata, 47 and 115, La Plata B1900BJW, Argentina.
authors.forename: Pablo
authors.initials: P
authors.lastname: Palestro
authors.affiliation: Università degli Studi di Firenze, Neurofarba Department, Sezione di Scienze Farmaceutiche e Nutraceutiche, Via U. Schiff 6, 50019 Sesto Fiorentino, Florence, Italy.
authors.forename: Mariangela
authors.initials: M
authors.lastname: Ceruso
authors.affiliation: Medicinal Chemistry, Department of Biological Sciences, Faculty of Exact Sciences, National University of La Plata, 47 and 115, La Plata B1900BJW, Argentina.
authors.forename: Jose L
authors.initials: JL
authors.lastname: Gonzalez Funes
authors.affiliation: Medicinal Chemistry, Department of Biological Sciences, Faculty of Exact Sciences, National University of La Plata, 47 and 115, La Plata B1900BJW, Argentina.
authors.forename: Alan
authors.initials: A
authors.lastname: Talevi
authors.affiliation: Medicinal Chemistry, Department of Biological Sciences, Faculty of Exact Sciences, National University of La Plata, 47 and 115, La Plata B1900BJW, Argentina.
authors.forename: Luis
authors.initials: L
authors.lastname: Bruno Blanch
authors.affiliation: Università degli Studi di Firenze, Neurofarba Department, Sezione di Scienze Farmaceutiche e Nutraceutiche, Via U. Schiff 6, 50019 Sesto Fiorentino, Florence, Italy. Electronic address: claudiu.supuran@unifi.it.
authors.forename: Claudiu T
authors.initials: CT
authors.lastname: Supuran
authors.affiliation: Medicinal Chemistry, Department of Biological Sciences, Faculty of Exact Sciences, National University of La Plata, 47 and 115, La Plata B1900BJW, Argentina. Electronic address: lgavernet@biol.unlp.edu.ar.
authors.forename: Luciana
authors.initials: L
authors.lastname: Gavernet
mesh_terms: D020816:Amino Acid Motifs; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000737:chemistry; D001665:Binding Sites; D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D002256:Carbonic Anhydrases / Q000737:chemistry*; D003494:Cyclamates / Q000737:chemistry; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000737:chemistry; D007700:Kinetics; D062105:Molecular Docking Simulation; D008969:Molecular Sequence Data; D011485:Protein Binding; D017433:Protein Structure, Secondary; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D000927:Anticonvulsants; D002257:Carbonic Anhydrase Inhibitors; D003494:Cyclamates; D007527:Isoenzymes; D013449:Sulfonamides; D002256:Carbonic Anhydrases; C477051:carbonic anhydrase VI
keywords: Carbonic anhydrase; Docking; Epilepsy; Sodium cyclamate; Sulfamides