Flucofuron as a Promising Therapeutic Agent against Brain-Eating Amoeba

  • ACS Infect Dis. 2024 Jun 14;10(6):2063-2073. doi: 10.1021/acsinfecdis.4c00062.
Javier Chao-Pellicer  1  2  3 ,  Iñigo Arberas-Jiménez  1  2 ,  Ines Sifaoui  1  2  3 ,  José E Piñero  1  2  3 ,  Jacob Lorenzo-Morales  1  2  3
Affiliations
  • 1. Instituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias, Universidad de La Laguna, Avda. Astrofísico Fco. Sánchez, S/N, 38203 San Cristóbal de La Laguna, Spain.
  • 2. Departamento de Obstetricia y Ginecología, Pediatría, Medicina Preventiva y Salud Pública, Toxicología, Medicina Legal y Forense y Parasitología, Universidad de La Laguna, 38203 San Cristóbal de La Laguna, Spain.
  • 3. Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, 28220 Madrid, Spain.
PMID: 38757533 DOI: 10.1021/acsinfecdis.4c00062
Abstract

Primary amoebic meningoencephalitis (PAM) is a rare and fulminant neurodegenerative disease caused by the free-living amoeba Naegleria fowleri. Currently, there is a lack of standardized protocols for therapeutic action. In response to the critical need for effective therapeutic agents, we explored the Global Health Priority Box, a collection of 240 compounds provided by the Medicines for Malaria Venture (MMV). From this pool, flucofuron emerged as a promising candidate, exhibiting high efficacy against trophozoites of both N. fowleri strains (ATCC 30808 IC50 : 2.58 ± 0.64 μM and ATCC 30215 IC50: 2.47 ± 0.38 μM), being even active against the resistant cyst stage (IC50: 0.88 ± 0.07 μM). Moreover, flucofuron induced diverse metabolic events that suggest the triggering of apoptotic cell death. This study highlights the potential of repurposing medications for treating challenging diseases, such as PAM.

Keywords
Global Health Priority Box; Naegleria fowleri; chemotherapy; flucofuron; programmed cell death.
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