title: Poly(amidoamine) Dendrimers with Carbonic Anhydrase Inhibitory Activity and Antiglaucoma Action.
abstract: Four generations of poly(amidoamine) (PAMAM) dendrimers decorated with benzenesulfonamide moieties were prepared by derivatizing the amino groups of the dendrimer with 4-carboxy-benzenesulfonamide functionalities. Compounds incorporating 4, 8, 16, and 32 sulfonamide moieties were thus obtained, which showed an increasing carbonic anhydrase (CA, EC 4.2.1.1) inhibitory action with the increase of the number of sulfamoyl groups in the dendrimer. Best inhibitory activity (in the low nanomolar-subnanomolar range) was observed for isoforms CA II and XII, involved among others in glaucoma. In an animal model of this disease, the chronic administration of such dendrimers for 5 days led to a much more efficient drop of intraocular pressure compared to the standard drug dorzolamide.
authors: †Laboratorio di Chimica Bioinorganica, Università degli Studi di Firenze, Rm. 188, Via della Lastruccia 3, I-50019 Sesto Fiorentino, Firenze, Italy.
authors: Fabrizio
authors: F
authors: Carta
authors: ‡Department of Chemistry, College of Science, King Saud University, P.O. Box 2455 Riyadh 11451, Saudi Arabia.
authors: Sameh M
authors: SM
authors: Osman
authors: †Laboratorio di Chimica Bioinorganica, Università degli Studi di Firenze, Rm. 188, Via della Lastruccia 3, I-50019 Sesto Fiorentino, Firenze, Italy.
authors: Daniela
authors: D
authors: Vullo
authors: †Laboratorio di Chimica Bioinorganica, Università degli Studi di Firenze, Rm. 188, Via della Lastruccia 3, I-50019 Sesto Fiorentino, Firenze, Italy.
authors: Antonella
authors: A
authors: Gullotto
authors: §Institut des Biomolécules Max Mousseron (IBMM), Ecole Nationale Supérieure de Chimie de Montpellier, UMR 5247 CNRS-ENSCM-Université de Montpellier , Bâtiment de Recherche Max Mousseron, 8 rue de l'Ecole Normale, 34296 Montpellier Cedex, France.
authors: Jean-Yves
authors: JY
authors: Winum
authors: ‡Department of Chemistry, College of Science, King Saud University, P.O. Box 2455 Riyadh 11451, Saudi Arabia.
authors: Zeid
authors: Z
authors: AlOthman
authors: ∥Dipartimento NEUROFARBA, Sezione di Farmacologia, Università degli Studi di Firenze, , Via G. Pierracini 6, 50139 Firenze, Italy.
authors: Emanuela
authors: E
authors: Masini
authors: ‡Department of Chemistry, College of Science, King Saud University, P.O. Box 2455 Riyadh 11451, Saudi Arabia.|⊥Polo Scientifico, Dipartimento NEUROFARBA, Sezione di Scienze Farmaceutiche e Nutraceutiche, Università degli Studi di Firenze, , Via Ugo Schiff 6, 50019 Sesto Fiorentino, Firenze, Italy.
authors: Claudiu T
authors: CT
authors: Supuran
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000378:metabolism; D024401:Carbonic Anhydrase I / Q000378:metabolism; D024402:Carbonic Anhydrase II / Q000378:metabolism; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000378:metabolism; D050091:Dendrimers / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D005901:Glaucoma / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D007429:Intraocular Pressure / Q000187:drug effects; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D008297:Male; D011073:Polyamines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011817:Rabbits; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000096926:Benzenesulfonamides
chemical_list: D000951:Antigens, Neoplasm; D024401:Carbonic Anhydrase I; D024402:Carbonic Anhydrase II; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases; D050091:Dendrimers; D007527:Isoenzymes; D011073:Polyamines; D013449:Sulfonamides; D000096926:Benzenesulfonamides; C531249:Poly(amidoamine); C089226:CA9 protein, human; C477378:carbonic anhydrase XII