Inhibition studies of the protozoan α-carbonic anhydrase from Trypanosoma cruzi with phenols

Alessandro Bonardi, Seppo Parkkila, Claudiu T. Supuran

Research output: Contribution to journalArticleScientificpeer-review

1 Downloads (Pure)

Abstract

The α-class carbonic anhydrase (CA, EC 4.2.1.1) from the protozoan pathogen Trypanosoma cruzi, TcCA, was investigated earlier for its inhibition with anions, sulphonamides, thiols and hydroxamates, well-known classes of CA inhibitors (CAIs). Here we present the first inhibition study of this enzyme with phenols, which possess a diverse CA inhibition mechanism compared to the previously investigated compounds, which are all zinc binders. Indeed, phenols are known to anchor to the zinc coordinated water molecule within the enzyme active site. In a series of 22 diversely substituted phenols, the best inhibitors were simple phenol, pyrocatechol, salicylic acid, 3,5-difluorophenol, 3,4-dihydroxy-benzoic acid, 3,6- dihydroxy-benzoic acid, caffeic acid and its des-hydroxy analog, with KIs of 1.8 - 7.3 µM. The least effective TcCA inhibitor was 3-chloro-4-amino-phenol (KI of 47.9 µM). Although it is not yet clear whether TcCA can be considered as an anti-Chagas disease drug target, as no animal model for investigating the antiprotozoan effects is available so far, finding effective in vitro inhibitors may be a first relevant step towards new antiprotozoal agents.

Original languageEnglish
Pages (from-to)2417-2422
Number of pages6
JournalJOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
Volume37
Issue number1
DOIs
Publication statusPublished - 2022
Publication typeA1 Journal article-refereed

Keywords

  • anti-protozoal action
  • Carbonic anhydrase
  • enzyme inhibition
  • phenol
  • Trypanosoma cruzi

Publication forum classification

  • Publication forum level 1

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery

Fingerprint

Dive into the research topics of 'Inhibition studies of the protozoan α-carbonic anhydrase from Trypanosoma cruzi with phenols'. Together they form a unique fingerprint.

Cite this