title: Antiobesity carbonic anhydrase inhibitors: a literature and patent review.
abstract: BACKGROUND
  Obesity is ranked as one of the top 10 global health problems and the major concern deriving from it is the exposure of the population to a vast array of chronic pathologies such as cardiovascular and musculoskeletal disorders, type 2 diabetes, cancer, such as colon, breast and endometrial cancer, together with psychological disorders derived from this condition. The discovery that the clinically used anticonvulsants topiramate (TPM) and zonisamide (ZNS) induced weight loss in obese, epileptic patients, afforded the validation of the mitochondrial carbonic anhydrases (CAs, EC 4.2.1.1) VA and VB as targets for the development of antiobesity drugs.
  
  
  METHODS
  This review deals with the scientific and patent literature regarding obesity or obesity-related pathologies, being particularly focused on the use of carbonic anhydrase inhibitors (CAI) such as TPM and ZNS which inhibit the de novo lipogenesis.
  
  
  CONCLUSIONS
  There is an urgent need of new drugs for the treatment of obesity. The identification that the mitochondrial CAs are implicated in the de novo lipogenesis allowed to consider selective inhibitors of such enzymes as useful for the development of new antiobesity drugs. Actually TPM was approved 1 year ago for this therapy, whereas ZNS is also an effective such agent. These compounds are the lead molecules in this field and an intense research is on the way in order to develop new compounds based on the selective inhibition of mitochondrial CA isoforms.
authors.affiliation: Università degli Studi di Firenze, Laboratorio di Chimica Bioinorganica, Rm. 188, Via della Lastruccia 3, I-50019 Sesto Fiorentino (Florence), Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Scozzafava
authors.forename: Claudiu T
authors.initials: CT
authors.lastname: Supuran
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Carta
mesh_terms: D000818:Animals; D019440:Anti-Obesity Agents / Q000494:pharmacology / Q000627:therapeutic use; D002257:Carbonic Anhydrase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D002256:Carbonic Anhydrases / Q000187:drug effects / Q000378:metabolism; D015195:Drug Design; D005632:Fructose / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007555:Isoxazoles / Q000494:pharmacology / Q000627:therapeutic use; D050155:Lipogenesis / Q000187:drug effects; D008928:Mitochondria / Q000201:enzymology; D058990:Molecular Targeted Therapy; D009765:Obesity / Q000188:drug therapy / Q000201:enzymology; D010330:Patents as Topic; D000077236:Topiramate; D000078305:Zonisamide
chemical_list: D019440:Anti-Obesity Agents; D002257:Carbonic Anhydrase Inhibitors; D007555:Isoxazoles; D000077236:Topiramate; D005632:Fructose; D000078305:Zonisamide; D002256:Carbonic Anhydrases