title: Monothiocarbamates Strongly Inhibit Carbonic Anhydrases in Vitro and Possess Intraocular Pressure Lowering Activity in an Animal Model of Glaucoma.
abstract: A series of monothiocarbamates (MTCs) were prepared from primary/secondary amines and COS as potential carbonic anhydrase (CA, EC 4.2.1.1) inhibitors, using the dithiocarbamates, the xanthates, and the trithiocarbonates as lead compounds. The MTCs effectively inhibited the pharmacologically relevant human (h) hCAs isoforms I, II, IX, and XII in vitro and showed KIs spanning between the low and medium nanomolar range. By means of a computational study, the MTC moiety binding mode on the CAs was explained. Furthermore, a selection of MTCs were evaluated in a normotensive glaucoma rabbit model for their intraocular pressure (IOP) lowering effects and showed interesting activity.
authors.affiliation: Polo Scientifico, Laboratorio di Chimica Bioinorganica, Università degli Studi di Firenze , Rm. 188, Via della Lastruccia 3, 50019 Sesto Fiorentino, Florence, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Vullo
authors.affiliation: Dipartimento NEUROFARBA, Sezione di Farmacologia, Università degli Studi di Firenze , Viale Pieraccini 6, 50139 Florence, Italy.
authors.forename: Mariaconcetta
authors.initials: M
authors.lastname: Durante
authors.affiliation: Department of Pharmacy, University of Naples "Federico II" , Via D. Montesano 49, 80131 Naples, Italy.
authors.forename: Francesco Saverio
authors.initials: FS
authors.lastname: Di Leva
authors.affiliation: DiSTABiF, Seconda Università di Napoli , Via Vivaldi 43, 81100 Caserta, Italy.
authors.forename: Sandro
authors.initials: S
authors.lastname: Cosconati
authors.affiliation: Dipartimento NEUROFARBA, Sezione di Farmacologia, Università degli Studi di Firenze , Viale Pieraccini 6, 50139 Florence, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Masini
authors.affiliation: Polo Scientifico, Laboratorio di Chimica Bioinorganica, Università degli Studi di Firenze , Rm. 188, Via della Lastruccia 3, 50019 Sesto Fiorentino, Florence, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Scozzafava
authors.affiliation: Department of Pharmacy, University of Naples "Federico II" , Via D. Montesano 49, 80131 Naples, Italy.
authors.forename: Ettore
authors.initials: E
authors.lastname: Novellino
authors.affiliation: Polo Scientifico, Laboratorio di Chimica Bioinorganica, Università degli Studi di Firenze , Rm. 188, Via della Lastruccia 3, 50019 Sesto Fiorentino, Florence, Italy.|Dipartimento NEUROFARBA, Sezione di Scienze Farmaceutiche, 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: Polo Scientifico, Laboratorio di Chimica Bioinorganica, Università degli Studi di Firenze , Rm. 188, Via della Lastruccia 3, 50019 Sesto Fiorentino, Florence, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Carta
mesh_terms: D000818:Animals; D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002256:Carbonic Anhydrases / Q000378:metabolism*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005901:Glaucoma / Q000188:drug therapy*; D006801:Humans; D007429:Intraocular Pressure / Q000187:drug effects*; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D008958:Models, Molecular; D015394:Molecular Structure; D011817:Rabbits; D013329:Structure-Activity Relationship
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D007527:Isoenzymes; D002256:Carbonic Anhydrases