title: Inhibition of carbonic anhydrase from Trypanosoma cruzi for the management of Chagas disease: an underexplored therapeutic opportunity.
abstract: An α-carbonic anhydrases (CAs, EC 4.2.1.1) was recently discovered, cloned and characterized in the genome of the protozoan parasite Trypanosoma cruzi, the causative agent of Chagas disease, a neglected but widespread tropical disease. Inhibition of this α-CAs (TcCA) with anions, sulfonamides, sulfamates, thiols and hydroxamates has been investigated in detail, with several low nanomolar in vitro inhibitors. Although the sulfonamides were the best in vitro inhibitors, they showed no ex vivo anti-T. cruzi activity, due to poor penetration. However, some thiols and hydroxamates acting as low nanomolar TcCA inhibitors also showed significant antitrypanosomal ex vivo activity, making this enzyme an attractive yet underexplored drug target for the management of Chagas disease.
authors.affiliation: Neurofarba Department, Sezione di Scienze Farmaceutiche e Nutraceutiche, Università degli Studi di Firenze, Via Ugo Schiff 6, I-50019 Sesto Fiorentino (Florence), Italy.
authors.forename: Claudiu T
authors.initials: CT
authors.lastname: Supuran
mesh_terms: D000595:Amino Acid Sequence; D002257:Carbonic Anhydrase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D002256:Carbonic Anhydrases / Q000378:metabolism*; D014355:Chagas Disease / Q000188:drug therapy* / Q000469:parasitology; D006801:Humans; D008969:Molecular Sequence Data; D015394:Molecular Structure; D014349:Trypanosoma cruzi / Q000201:enzymology*
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D002256:Carbonic Anhydrases
keywords: Trypanosoma cruzi; anti-infective; carbonic anhydrase; metalloenzyme; polyamine; protozoan; sulfamate; sulfonamide; thiol