title: Dual Cyclooxygenase and Carbonic Anhydrase Inhibition by Nonsteroidal Anti-Inflammatory Drugs for the Treatment of Cancer.
abstract: Among the class of nonsteroidal anti-inflammatory drugs (NSAIDs), COX-2 inhibitors or "coxibs" selectively inhibit the activity of the inducible isoform of cyclooxygenase. Moreover, there is emerging evidence that the sulfonamide-type coxibs, but not the methylsulfones, display an inhibitory activity also against several isoforms of human carbonic anhydrase (CA, EC 4.2.1.1). In this regard, celecoxib and valdecoxib, possessing a primary sulfonamide that binds to the zinc ion at the active site of the enzyme, are nanomolar inhibitors of the cancer-related hCA IX isoform. Also meloxicam and lornoxicam, NSAIDs belonging to the class of "oxicams", that contain a cyclic tertiary sulfonamide moiety, inhibit this isoform at low micromolar concentrations. The multiple pharmacological effects of the sulfonamide anti-inflammatory agents could be ascribed to the dual inhibition of CA and COX enzymes, supporting the evidence that inflammation and hypoxia pathways are involved in cancer onset and progression and suggesting that the antitumoral activity of these compounds should be further explored for their possible use in the polypharmacology of cancer prevention and therapy.
authors.affiliation: Sapienza University of Rome, Department of Drug Chemistry and Technologies, 00185 - Rome, Italy. celeste.demonte@uniroma1.it.
authors.forename: Celeste
authors.initials: C
authors.lastname: De Monte
authors.forename: Simone
authors.initials: S
authors.lastname: Carradori
authors.forename: Andrea
authors.initials: A
authors.lastname: Gentili
authors.forename: Adriano
authors.initials: A
authors.lastname: Mollica
authors.forename: Daniela
authors.initials: D
authors.lastname: Trisciuoglio
authors.forename: Claudiu T
authors.initials: CT
authors.lastname: Supuran
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use; D002257:Carbonic Anhydrase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D013449:Sulfonamides / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D002257:Carbonic Anhydrase Inhibitors; D052246:Cyclooxygenase 2 Inhibitors; D013449:Sulfonamides