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Title

Cyclolauranes as plausible chemical scaffold against Naegleria fowleri

AuthorsArberas-Jiménez, Íñigo; García-Davis, Sara; Rizo-Liendo, Aitor; Sifaoui, Inés; Quintana Morales, Ezequiel CSIC ; Piñero, José E.; Lorenzo-Morales, Jacob; Díaz-Marrero, Ana R. CSIC ORCID; Fernández, José J.
KeywordsDebromolaurinterol
Laurinterol
Naegleria fowleri
Cyclolaurane
Primary amoebic meningoencephalitis
ATPase
Issue Date11-Mar-2022
PublisherElsevier
CitationBiomedicine and Pharmacotherapy 149, 112816: 1-11 (2022)
AbstractPrimary amoebic meningoencephalitis (PAM) is a central nervous system (CNS) disease caused by Naegleria fowleri that mainly affects children and young adults with fatal consequences in most of the cases. Treatment protocols are based on the combination of different antimicrobial agents, nonetheless there is the need to develop new anti-Naegleria compounds with low toxicity and full effects compared to the currently used drug combination. The marine environment is a well-established source of bioactive natural products. In this work, we have focused on the structure of Laurencia cyclolaurane-type sesquiterpenes as potential chemical model against Naegleria species. The effects of debromolaurinterol (1) to induce PCD/apoptosis-like events in Naegleria fowleri have been evaluated, revealing that this compound induced reduction of ATP production showing a decrease of 99.98% in treated parasite cells. A SAR analysis have been supported with molecular modeling and analysis of the in silico ADME/Tox properties of the Laurencia sesquiterpenes debromolaurinterol (1), laurinterol (2) and allolaurinterol (3), which reinforce cyclolaurane metabolites as plausible molecular models to develop PAM treatments.
Publisher version (URL)https://doi.org/10.1016/j.biopha.2022.112816
URIhttp://hdl.handle.net/10261/264308
DOI10.1016/j.biopha.2022.112816
ISSN0753-3322
E-ISSN1950-6007
Appears in Collections:(IPNA) Artículos




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