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7912150 
Journal Article 
Laurinterol from Laurencia johnstonii eliminates Naegleria fowleri triggering PCD by inhibition of ATPases 
Arberas-Jiménez, I; García-Davis, S; Rizo-Liendo, A; Sifaoui, I; Reyes-Batlle, M; Chiboub, O; Rodríguez-Expósito, RL; Díaz-Marrero, AR; Piñero, JE; Fernández, JJ; Lorenzo-Morales, J 
2020 
1 
Scientific Reports
EISSN: 2045-2322 
10 
1 
17731 
English 
33082417 
WOS:000585233000013 
Primary amoebic encephalitis (PAM) is a lethal disease caused by the opportunistic pathogen, Naegleria fowleri. This amoebic species is able to live freely in warm aquatic habitats and to infect children and young adults when they perform risk activities in these water bodies such as swimming or splashing. Besides the need to increase awareness of PAM which will allow an early diagnosis, the development of fully effective therapeutic agents is needed. Current treatment options are amphotericin B and miltefosine which are not fully effective and also present toxicity issues. In this study, the in vitro activity of various sesquiterpenes isolated from the red alga Laurencia johnstonii were tested against the trophozoite stage of a strain of Naegleria fowleri. Moreover, the induced effects (apoptotic cell death) of the most active compound, laurinterol (1), was evaluated by measuring DNA condensation, damages at the mitochondrial level, cell membrane disruption and production of reactive oxygen species (ROS). The obtained results demonstrated that laurinterol was able to eliminate the amoebae at concentrations of 13.42 ± 2.57 µM and also to induced programmed cell death (PCD) in the treated amoebae. Moreover, since ATP levels were highly affected and laurinterol has been previously reported as an inhibitor of the Na+/K+-ATPase sodium-potassium ion pump, comparison with known inhibitors of ATPases were carried out. Our results points out that laurinterol was able to inhibit ENA ATPase pump at concentrations 100 times lower than furosemide. 
Adenosine Triphosphate metabolism; Amphotericin B therapeutic use; Antiparasitic Agents metabolism; Antiparasitic Agents pharmacology; Apoptosis drug effects; Central Nervous System Protozoal Infections drug therapy; DNA Damage drug effects; Humans; Laurencia metabolism; Naegleria fowleri physiology; Phosphorylcholine analogs & derivatives; Phosphorylcholine therapeutic use; Protozoan Proteins antagonists & inhibitors; Reactive Oxygen Species metabolism; Sesquiterpenes metabolism; Sesquiterpenes pharmacology; Sodium-Potassium-Exchanging ATPase antagonists & inhibitors; Trophozoites drug effects; Trophozoites physiology; Index Medicus