Programmed cell death in Naegleria fowleri induced by frutescinol acetate, a polyacetylene from Argyranthemum

Suhib Muhsen Hasan Aldalaeen1, Javier Chao-Pellicer2, Ines Sifaoui2

  • 1Instituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias, Universidad de La Laguna, 38296 San Cristóbal de La Laguna, Santa Cruz de Tenerife, Spain.

Abstract

Insights

A novel compound, frutescinol acetate, from Argyranthemum frutescens shows potent activity against Naegleria fowleri, the cause of primary amoebic meningoencephalitis (PAM). This natural compound effectively kills both trophozoite and cyst forms, offering a promising new avenue for PAM treatment.

Area of Science:

  • Natural Product Chemistry
  • Parasitology
  • Pharmacology

Background:

  • Primary amoebic meningoencephalitis (PAM) is a devastating infection caused by Naegleria fowleri with limited treatment options.
  • Investigating natural compounds offers a promising strategy for developing new anti-PAM therapies.

Purpose of the Study:

  • To isolate and characterize a bioactive metabolite from Argyranthemum frutescens with amoebicidal activity against Naegleria fowleri.
  • To elucidate the mechanism of action of this natural compound against N. fowleri.

Main Methods:

  • Bio-guided fractionation of Argyranthemum frutescens root extract to isolate the active compound.
  • Testing the isolated compound's activity against N. fowleri trophozoites and cysts, comparing it to miltefosine.
  • Assessing cytotoxicity in a murine macrophage cell line and investigating programmed cell death markers.

Main Results:

  • Frutescinol acetate, a polyacetylene, demonstrated potent activity against N. fowleri trophozoites (IC₅₀ 4.97–5.70 µM) and cysts (IC₅₀ 8.53 µM), outperforming miltefosine.
  • The compound exhibited a favorable selectivity profile with low cytotoxicity.
  • Frutescinol acetate induced programmed cell death in N. fowleri, evidenced by chromatin condensation, membrane permeability changes, mitochondrial dysfunction, and ROS production.

Conclusions:

  • Frutescinol acetate is a potent amoebicidal agent against Naegleria fowleri.
  • The compound induces programmed cell death-like mechanisms in N. fowleri.
  • Frutescinol acetate shows potential as a lead compound for developing new treatments for PAM.

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