Activation studies with amines and amino acids of the α-carbonic anhydrase from the pathogenic protozoan Trypanosoma cruzi

Bioorg Med Chem. 2018 Aug 7;26(14):4187-4190. doi: 10.1016/j.bmc.2018.07.011. Epub 2018 Jul 7.

Abstract

The activation of a α-class carbonic anhydrase (CAs, EC 4.2.1.1) from Trypanosoma cruzi (TcCA) was investigated with the best known classes of activators, the amino acids and aromatic/heterocyclic amines. The best TcCA activators were l-/d-DOPA and 4-amino-l-phenylalanine, which had activation constants in the range of 0.38-0.83 µM. Low micromolar activators were also l-/d-Trp, l-/d-Tyr, l-Gln, histamine and serotonin (KAs of 1.79-4.92 µM), whereas l-/d-His, l-/d-Phe and l-Asp were less effective activators (KAs of 6.39-18.7 µM). Amines such as dopamine, pyridyl-alkylamines, aminoethyl-piperazine or l-adrenaline, were devoid of activating effects on TcCA. Since the role of autacoids as many of these compounds investigated here is not known for the life cycle of T. cruzi, our work provides new tools for further investigations of factors connected with this protozoan pathogen infection.

Keywords: Activators; Carbonic anhydrase; Metalloenzymes; Pathogens; Trypanosoma cruzi.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amines / chemistry
  • Amines / pharmacology*
  • Amino Acids / chemistry
  • Amino Acids / pharmacology*
  • Carbonic Anhydrases / metabolism*
  • Dose-Response Relationship, Drug
  • Humans
  • Molecular Structure
  • Structure-Activity Relationship
  • Trypanosoma cruzi / enzymology*
  • Trypanosoma cruzi / metabolism
  • Trypanosoma cruzi / pathogenicity

Substances

  • Amines
  • Amino Acids
  • Carbonic Anhydrases