title: Carbonic anhydrase inhibitors. Inhibition of human cytosolic isoforms I and II with (reduced) Schiff's bases incorporating sulfonamide, carboxylate and carboxymethyl moieties.
abstract: A library of Schiff bases was synthesized by condensation of aromatic amines incorporating sulfonamide, carboxylic acid or carboxymethyl functionalities as Zn(2+)-binding groups, with aromatic aldehydes incorporating tert-butyl, hydroxy and/or methoxy groups. The corresponding amines were thereafter obtained by reduction of the imines. These compounds were assayed for the inhibition of two cytosolic human carbonic anhydrase (hCA, EC 4.2.1.1) isoenzymes, hCA I and II. The Ki values of the Schiff bases were in the range of 7.0-21,400nM against hCA II and of 52-8600nM against hCA I, respectively. The corresponding amines showed Ki values in the range of 8.6nM-5.3μM against hCA II, and of 18.7-251nM against hCA I, respectively. Unlike the imines, the reduced Schiff bases are stable to hydrolysis and several low-nanomolar inhibitors were detected, most of them incorporating sulfonamide groups. Some carboxylates also showed interesting CA inhibitory properties. Such hydrosoluble derivatives may show pharmacologic applications.
authors.affiliation: Adaptive Supramolecular Nanosystems Group, Institut Européen des Membranes, ENSCM/UMII/UMR-CNRS 5635, Place Eugène Bataillon, CC 047, 34095 Montpellier, Cedex 5, France.
authors.forename: Gihane
authors.initials: G
authors.lastname: Nasr
authors.affiliation: Adaptive Supramolecular Nanosystems Group, Institut Européen des Membranes, ENSCM/UMII/UMR-CNRS 5635, Place Eugène Bataillon, CC 047, 34095 Montpellier, Cedex 5, France.
authors.forename: Alina
authors.initials: A
authors.lastname: Cristian
authors.affiliation: Adaptive Supramolecular Nanosystems Group, Institut Européen des Membranes, ENSCM/UMII/UMR-CNRS 5635, Place Eugène Bataillon, CC 047, 34095 Montpellier, Cedex 5, France. Electronic address: mihail-dumitru.barboiu@univ-montp2.fr.
authors.forename: Mihail
authors.initials: M
authors.lastname: Barboiu
authors.affiliation: Università degli Studi di Firenze, Polo Scientifico, Laboratorio di Chimica Bioinorganica, Rm. 188, Via della Lastruccia 3, 50019 Sesto Fiorentino (Florence), Italy.
authors.forename: Daniella
authors.initials: D
authors.lastname: Vullo
authors.affiliation: Institut des Biomolécules Max Mousseron (IBMM) UMR 5247 CNRS-UM1-UM2 Bâtiment de Recherche Max Mousseron, Ecole Nationale Supérieure de Chimie de Montpellier, 8 rue de l'Ecole Normale, 34296 Montpellier Cedex, France.
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Winum
authors.affiliation: Università degli Studi di Firenze, Polo Scientifico, Laboratorio di Chimica Bioinorganica, Rm. 188, Via della Lastruccia 3, 50019 Sesto Fiorentino (Florence), Italy; Università degli Studi di Firenze, Polo Scientifico, Dipartimento NEUROFABA, Sezione di Scienze Farmaceutiche e Nutraceutiche, Via Ugo Schiff 6, 50019 Sesto Fiorentino (Firenze), Italy. Electronic address: claudiu.supuran@unifi.it.
authors.forename: Claudiu T
authors.initials: CT
authors.lastname: Supuran
mesh_terms: D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002256:Carbonic Anhydrases / Q000378:metabolism*; D002264:Carboxylic Acids / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D015394:Molecular Structure; D012545:Schiff Bases / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry*
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D002264:Carboxylic Acids; D007527:Isoenzymes; D012545:Schiff Bases; D013449:Sulfonamides; D002256:Carbonic Anhydrases
keywords: Amine; Carbonic anhydrase; Imine; Inhibitor; Schiff’s base; Sulfonamide