title: Fluorescent Silica Nanoparticles with Multivalent Inhibitory Effects towards Carbonic Anhydrases.
abstract: Multifunctional silica nanoparticles decorated with fluorescent and sulfonamide carbonic anhydrase (CA) inhibitors were prepared and investigated as multivalent enzyme inhibitors against the cytosolic isoforms hCA I and II and the transmembrane tumor-associated ones hCA IX and XII. Excellent inhibitory effects were observed with these nanoparticles, with KI values in the low nanomolar range (6.2-0.67 nM) against all tested isozymes. A significant multivalency effect was seen for the inhibition of the monomeric enzymes hCA I and II compared to the dimeric hCA IX and hCA XII isoforms, where no multivalent effect was observed, suggesting that the multivalent binding is occurring through enzyme clustering.
authors.affiliation: Institut des Biomolécules Max Mousseron (IBMM), UMR 5247 CNRS-ENSCM-Université de Montpellier, ENSCM, 8 rue de l'Ecole Normale, 34296 Montpellier Cedex (France).
authors.forename: Nadia
authors.initials: N
authors.lastname: Touisni
authors.affiliation: Institut des Biomolécules Max Mousseron (IBMM), UMR 5247 CNRS-ENSCM-Université de Montpellier, ENSCM, 8 rue de l'Ecole Normale, 34296 Montpellier Cedex (France).
authors.forename: Nasreddine
authors.initials: N
authors.lastname: Kanfar
authors.affiliation: Institut des Biomolécules Max Mousseron (IBMM), UMR 5247 CNRS-ENSCM-Université de Montpellier, ENSCM, 8 rue de l'Ecole Normale, 34296 Montpellier Cedex (France).
authors.forename: Sébastien
authors.initials: S
authors.lastname: Ulrich
authors.affiliation: Institut des Biomolécules Max Mousseron (IBMM), UMR 5247 CNRS-ENSCM-Université de Montpellier, ENSCM, 8 rue de l'Ecole Normale, 34296 Montpellier Cedex (France).
authors.forename: Pascal
authors.initials: P
authors.lastname: Dumy
authors.affiliation: Neurofarba Department, Section of Pharmaceutical and Nutriceutical Sciences, Università degli Studi di Firenze, Via Ugo Schiff 6, 50019 Sesto Fiorentino, Florence (Italy).
authors.forename: Claudiu T
authors.initials: CT
authors.lastname: Supuran
authors.affiliation: Institut Charles Gerhardt, UMR 5253, Equipe Chimie Moléculaire et Organisation du Solide, Université de Montpellier, Place Eugène Bataillon, 34095 Montpellier Cedex 05 (France).
authors.forename: Ahmad
authors.initials: A
authors.lastname: Mehdi
authors.affiliation: Institut des Biomolécules Max Mousseron (IBMM), UMR 5247 CNRS-ENSCM-Université de Montpellier, ENSCM, 8 rue de l'Ecole Normale, 34296 Montpellier Cedex (France). jean-yves.winum@univ-montp2.fr.
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Winum
mesh_terms: D000951:Antigens, Neoplasm / Q000737:chemistry* / Q000378:metabolism; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D024401:Carbonic Anhydrase I / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D024402:Carbonic Anhydrase II / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D002257:Carbonic Anhydrase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D002256:Carbonic Anhydrases / Q000378:metabolism; D045744:Cell Line, Tumor; D003600:Cytosol / Q000737:chemistry / Q000187:drug effects* / Q000201:enzymology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D015394:Molecular Structure; D053758:Nanoparticles / Q000737:chemistry*; D009369:Neoplasms / Q000737:chemistry* / Q000188:drug therapy* / Q000201:enzymology; D012822:Silicon Dioxide / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D002257:Carbonic Anhydrase Inhibitors; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D012822:Silicon Dioxide; D024401:Carbonic Anhydrase I; D024402:Carbonic Anhydrase II; D002256:Carbonic Anhydrases
keywords: carbonic anhydrase; inhibitors; multivalency; nanoparticles; sulfonamide