title: Advances in structure-based drug discovery of carbonic anhydrase inhibitors.
abstract: The enzyme carbonic anhydrase (CA, EC 4.2.1.1) is found in numerous organisms across the tree of life, with seven distinct classes known to date. CA inhibition can be exploited for the treatment of edema, glaucoma, seizures, obesity, cancer and infectious diseases. A myriad of CA inhibitor (CAI) classes and inhibition mechanisms have been identified over the past decade, mainly through structure-based drug design approaches. Five different CA inhibition mechanisms are presently known. Areas covered: Recent advances in structure-based CAI design are reviewed, with periodic table-based organization of inhibitor classes. Expert opinion: Various structure-based drug design studies have led to deep understanding of factors governing tight binding and selectivity for the various isoforms. Carboxylic acids, phenols, polyamines, diols, borols, boronic acids, coumarins and sulfonamides represent successful stories which led to an anti-tumor sulfonamide in Phase I clinical trials (SLC-0111). For many inhibitor classes, no detailed crystallographic data are available. Detailed structural characterization of all CAI classes may lead to further advances in the field with potential therapeutic implications in the management of indications including neuropathic pain, cerebral ischemia, arthritis and tumor imaging.
authors: a Neurofarba Department, Sezione di Scienze Farmaceutiche e Nutraceutiche , Università degli Studi di Firenze , Sesto Fiorentino (Florence) , Italy.
authors: Claudiu T
authors: CT
authors: Supuran
mesh_terms: D000818:Animals; D002257:Carbonic Anhydrase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D002256:Carbonic Anhydrases / Q000187:drug effects / Q000378:metabolism; D015195:Drug Design; D055808:Drug Discovery / Q000379:methods*; D006801:Humans; D013329:Structure-Activity Relationship
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D002256:Carbonic Anhydrases
keywords: Carbonic anhydrase; X-ray crystallography; coumarin; dithiocarbamate; inhibition mechanism; inhibitor; sulfonamide