Marine Meroterpenoids Isolated from Gongolaria abies-marina Induce Programmed Cell Death in Naegleria fowleri. 2023

Iñigo Arberas-Jiménez, and Rubén L Rodríguez-Expósito, and Desirée San Nicolás-Hernández, and Javier Chao-Pellicer, and Ines Sifaoui, and Ana R Díaz-Marrero, and José J Fernández, and José E Piñero, and Jacob Lorenzo-Morales
Instituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias, Universidad de La Laguna, Avda. Astrofísico Fco. Sánchez, S/N, 38206 La Laguna, Tenerife, Spain.

Naegleria fowleri is the causative agent of a central nervous system affecting disease called primary amoebic meningoencephalitis. It is a fulminant disease with a rapid progression that affects mainly children and young adults who report previous water exposure. Current treatment options are not totally effective and involve several side effects. In this work, six meroterpenoids isolated from the brown algae Gongolaria abies-marina were evaluated against N. fowleri. Gongolarone B (1), 6Z-1'-methoxyamentadione (2), and 1'-methoxyamentadione (3) were the most active molecules against N. fowleri with IC50 values between 13.27 ± 0.96 µM and 21.92 ± 1.60 µM. However, cystomexicone B (6) was the molecule with the highest selectivity index (>8.5). Moreover, all these compounds induced different cellular events compatible with the apoptosis-like PCD process, such as chromatin condensation, damages at the mitochondrial level, cell membrane disruption, and production of reactive oxygen species (ROS). Therefore, G. abies-marina could be considered as a promising source of active molecules to treat the N. fowleri infections.

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