title: Dipotassium-trioxohydroxytetrafluorotriborate, K₂[B₃O₃F₄OH], is a potent inhibitor of human carbonic anhydrases.
abstract: The boron heterocyclic compound dipotassium-trioxohydroxytetrafluorotriborate (K2[B3O3F4OH]) was investigated as inhibitor of the zinc enzyme, carbonic anhydrase (CA, EC 4.2.1.1). Eleven human (h) CA isoforms, hCA I-IV, VA, VI, VII, IX and XII-XIV, were included in the investigations. The anion, similar to tetraborate or phenylboronic acid, inhibited most of them. hCA III was not inhibited by K2[B3O3F4OH], whereas hCA VA, hCA VI, hCA IX and hCA XIII were inhibited in the submillimolar range, with KIs of 0.31-0.63 mM. hCA I and II (cytosolic, widespread isoforms), hCA IV (membrane-bound isoform), hCA XII (tumor-associated, transmembrane) and hCA XIV (transmembrane) were much more effectively inhibited by this anion, with inhibition constants ranging from 25 to 93 µM. hCA VII, a cytosolic enzyme present in the brain and associated to oxidative stress, was very effectively inhibited by K2[B3O3F4OH], with a KI of 8.0 µM. We propose that K2[B3O3F4OH] binds to the metal ion from the enzyme active site, coordinating to the Zn(II) ion monodentately through its B-OH functionality. We hypothesize that some of the beneficial antitumor effects reported for K2[B3O3F4OH] may be due to the inhibition of CAs present in skin tumors.
authors.affiliation: Polo Scientifico, Laboratorio di Chimica Bioinorganica, Università degli Studi di Firenze , Sesto Fiorentino (Florence) , Italy .
authors.forename: Daniela
authors.initials: D
authors.lastname: Vullo
authors.forename: Mladen
authors.initials: M
authors.lastname: Milos
authors.forename: Borivoj
authors.initials: B
authors.lastname: Galic
authors.forename: Andrea
authors.initials: A
authors.lastname: Scozzafava
authors.forename: Claudiu T
authors.initials: CT
authors.lastname: Supuran
mesh_terms: D001896:Boron Compounds / Q000737:chemistry / Q000494:pharmacology*; D002257:Carbonic Anhydrase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D002256:Carbonic Anhydrases / Q000378:metabolism*; D020134:Catalytic Domain; D006801:Humans; D007527:Isoenzymes; D007700:Kinetics; D015394:Molecular Structure; D011994:Recombinant Proteins
chemical_list: D001896:Boron Compounds; D002257:Carbonic Anhydrase Inhibitors; D007527:Isoenzymes; D011994:Recombinant Proteins; C561431:dipotassium trioxohydroxytetrafluorotriborate; D002256:Carbonic Anhydrases
keywords: Anion; carbonic anhydrase; dipotassium-trioxohydroxytetrafluorotriborate; inhibitor