title: Non-Classical Inhibition of Carbonic Anhydrase.
abstract: Specific isoforms from the carbonic anhydrase (CA) family of zinc metalloenzymes have been associated with a variety of diseases. Isoform-specific carbonic anhydrase inhibitors (CAIs) are therefore a major focus of attention for specific disease treatments. Classical CAIs, primarily sulfonamide-based compounds and their bioisosteres, are examined as antiglaucoma, antiepileptic, antiobesity, antineuropathic pain and anticancer compounds. However, many sulfonamide compounds inhibit all CA isoforms nonspecifically, diluting drug effectiveness and causing undesired side effects due to off-target inhibition. In addition, a small but significant percentage of the general population cannot be treated with sulfonamide-based compounds due to a sulfa allergy. Therefore, CAIs must be developed that are not only isoform specific, but also non-classical, i.e. not based on sulfonamides, sulfamates, or sulfamides. This review covers the classes of non-classical CAIs and the recent advances in the development of isoform-specific inhibitors based on phenols, polyamines, coumarins and their derivatives.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Florida, Gainesville, FL 32611, USA. clomelino@ufl.edu.
authors.forename: Carrie L
authors.initials: CL
authors.lastname: Lomelino
authors.affiliation: Neurofarba Department, University of Florence, Piazza di San Marco, Firenze 50019, Italy. claudiu.supuran@unifi.it.
authors.forename: Claudiu T
authors.initials: CT
authors.lastname: Supuran
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Florida, Gainesville, FL 32611, USA. rmckenna@ufl.edu.
authors.forename: Robert
authors.initials: R
authors.lastname: McKenna
mesh_terms: D000818:Animals; D002257:Carbonic Anhydrase Inhibitors / Q000494:pharmacology*; D002256:Carbonic Anhydrases / Q000737:chemistry*; D006801:Humans
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D002256:Carbonic Anhydrases
keywords: carbonic anhydrase; carboxylate; coumarin; non-classical