In vitro activity and mechanism of cell death induction of cyanomethyl vinyl ethers derivatives against Trypanosoma cruzi

Int J Parasitol Drugs Drug Resist. 2023 Aug:22:72-80. doi: 10.1016/j.ijpddr.2023.05.001. Epub 2023 May 31.

Abstract

Chagas disease causes a problematic pathology that can lead to megacolon and heart disease, and can even cause the death of the patient. Current therapies for this disease are the same as they were 50 years ago, are not fully effective and have strong side effects. The lack of a safe and effective therapy makes it necessary to search for new, less toxic and totally effective compounds against this parasite. In this work, the antichagasic activity of 46 novel cyanomethyl vinyl ether derivatives was studied. In addition, to elucidate the type of cell death that these compounds produce in parasites, several events related to programmed cell death were studied. The results highlight four more selective compounds, E63, E64, E74 and E83, which also appear to trigger programmed cell death, and are therefore postulated as good candidates to use in future therapeutics for Chagas disease.

Keywords: Activity; Cell death; Chagas; Cyano; Trypanosoma cruzi.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Death
  • Chagas Disease* / drug therapy
  • Chagas Disease* / parasitology
  • Ethers / therapeutic use
  • Humans
  • Parasites*
  • Trypanocidal Agents* / pharmacology
  • Trypanocidal Agents* / therapeutic use
  • Trypanosoma cruzi*

Substances

  • vinyl ether
  • Trypanocidal Agents
  • Ethers