Inhibition of the newly discovered β‑carbonic anhydrase from the protozoan pathogen Trichomonas vaginalis with inorganic anions and small molecules

J Inorg Biochem. 2020 Dec:213:111274. doi: 10.1016/j.jinorgbio.2020.111274. Epub 2020 Oct 7.

Abstract

The protozoan pathogen Trichomonas vaginalis encodes two carbonic anhydrases (CAs, EC 4.2.1.1) belonging to the β-class. One of these enzymes, T. vaginalis carbonic anhydrase 1 (TvaCA1), was recently cloned and characterized by our group, and its X-ray crystal structure reported. No inhibitors of this enzyme were reported up until now. Here we investigated the inhibition of TvaCA1 with inorganic anions and small molecules and observed that thiocyanate, cyanide, selenite, selenocyanate and divanadate are sub-millimolar inhibitors, whereas sulfamide, sulfate, phenylboronic acid and phenylarsonic acid are micromolar inhibitors. Finding effective TvaCA1 inhibitors may be useful for developing new antiprotozoan drugs.

Keywords: Anion; Beta-class enzyme; Carbonic anhydrase; Inhibitor; Trichomonas vaginalis; Trichomoniasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anions
  • Antiprotozoal Agents / therapeutic use
  • Carbonic Anhydrase Inhibitors / pharmacology*
  • Carbonic Anhydrase Inhibitors / therapeutic use
  • Carbonic Anhydrases / chemistry
  • Carbonic Anhydrases / drug effects*
  • Female
  • Humans
  • Inorganic Chemicals / pharmacology*
  • Protein Conformation
  • Small Molecule Libraries / pharmacology*
  • Trichomonas Vaginitis / drug therapy
  • Trichomonas vaginalis / enzymology*

Substances

  • Anions
  • Antiprotozoal Agents
  • Carbonic Anhydrase Inhibitors
  • Inorganic Chemicals
  • Small Molecule Libraries
  • Carbonic Anhydrases