Literature DB >> 24939103

Dipotassium-trioxohydroxytetrafluorotriborate, K₂[B₃O₃F₄OH], is a potent inhibitor of human carbonic anhydrases.

Daniela Vullo1, Mladen Milos, Borivoj Galic, Andrea Scozzafava, Claudiu T Supuran.   

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.

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Keywords:  Anion; carbonic anhydrase; dipotassium-trioxohydroxytetrafluorotriborate; inhibitor

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Year:  2014        PMID: 24939103     DOI: 10.3109/14756366.2014.918610

Source DB:  PubMed          Journal:  J Enzyme Inhib Med Chem        ISSN: 1475-6366            Impact factor:   5.051


  2 in total

1.  Advantages of an Electrochemical Method Compared to the Spectrophotometric Kinetic Study of Peroxidase Inhibition by Boroxine Derivative.

Authors:  Jelena Ostojić; Safija Herenda; Zerina Bešić; Mladen Miloš; Borivoj Galić
Journal:  Molecules       Date:  2017-07-05       Impact factor: 4.411

2.  In vitro and in vivo antitumour effects of phenylboronic acid against mouse mammary adenocarcinoma 4T1 and squamous carcinoma SCCVII cells.

Authors:  Maja Marasovic; Sinisa Ivankovic; Ranko Stojkovic; Damir Djermic; Borivoj Galic; Mladen Milos
Journal:  J Enzyme Inhib Med Chem       Date:  2017-12       Impact factor: 5.051

  2 in total

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