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It is the causative agent of the primary amoebic meningoencephalitis. Focused on our interest to develop promising lead structures for the development of antiparasitic agents, this study was aimed at identifying new anti-Naegleria marine natural products from a collection of chamigrane-type sesquiterpenes with structural variety in the levels of saturation, halogenation and oxygenation isolated from Laurencia dendroidea. (+)-Elatol (1) was the most active compound against Naegleria fowleri trophozoites with IC50 values of 1.08 \u03bcM against the ATCC 30808\u2122 strain and 1.14 \u03bcM against the ATCC 30215\u2122 strain. Furthermore, the activity of (+)-elatol (1) against the resistant stage of N. fowleri was also assessed, showing great cysticidal properties with a very similar IC50 value (1.14 \u00b5M) to the one obtained for the trophozoite stage. Moreover, at low concentrations (+)-elatol (1) showed no toxic effect towards murine macrophages and could induce the appearance of different cellular events related to the programmed cell death, such as an increase of the plasma membrane permeability, reactive oxygen species overproduction, mitochondrial malfunction or chromatin condensation. Its enantiomer (\u2212)-elatol (2) was shown to be 34-fold less potent with an IC50 of 36.77 \u03bcM and 38.03 \u03bcM. An analysis of the structure\u2013activity relationship suggests that dehalogenation leads to a significant decrease of activity. The lipophilic character of these compounds is an essential property to cross the blood-brain barrier, therefore they represent interesting chemical scaffolds to develop new drugs.<\/jats:p>","DOI":"10.3390\/md21040224","type":"journal-article","created":{"date-parts":[[2023,3,31]],"date-time":"2023-03-31T08:27:27Z","timestamp":1680251247000},"page":"224","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Chamigrane-Type Sesquiterpenes from Laurencia dendroidea as Lead Compounds against Naegleria fowleri"],"prefix":"10.3390","volume":"21","author":[{"given":"I\u00f1igo","family":"Arberas-Jim\u00e9nez","sequence":"first","affiliation":[{"name":"Instituto Universitario de Enfermedades Tropicales y Salud P\u00fablica de Canarias, Universidad de La Laguna (ULL), Avda. Astrof\u00edsico Fco. S\u00e1nchez, S\/N, 38206 La Laguna, Tenerife, Islas Canarias, Spain"},{"name":"Departamento de Obstetricia y Ginecolog\u00eda, Pediatr\u00eda, Medicina Preventiva y Salud P\u00fablica, Toxicolog\u00eda, Medicina Legal y Forense y Parasitolog\u00eda, Universidad de La Laguna (ULL), 38206 La Laguna, Tenerife, Islas Canarias, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nath\u00e1lia","family":"Nocchi","sequence":"additional","affiliation":[{"name":"Instituto Universitario de Bio-Org\u00e1nica Antonio Gonz\u00e1lez (IUBO AG), Universidad de La Laguna (ULL), Avda. Astrof\u00edsico Fco. S\u00e1nchez 2, 38206 La Laguna, Tenerife, Islas Canarias, Spain"},{"name":"Departamento de Qu\u00edmica Org\u00e1nica, Universidad de La Laguna (ULL), Avda. Astrof\u00edsico Fco. S\u00e1nchez 3, 38206 La Laguna, Tenerife, Islas Canarias, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Chao-Pellicer","sequence":"additional","affiliation":[{"name":"Instituto Universitario de Enfermedades Tropicales y Salud P\u00fablica de Canarias, Universidad de La Laguna (ULL), Avda. Astrof\u00edsico Fco. S\u00e1nchez, S\/N, 38206 La Laguna, Tenerife, Islas Canarias, Spain"},{"name":"Departamento de Obstetricia y Ginecolog\u00eda, Pediatr\u00eda, Medicina Preventiva y Salud P\u00fablica, Toxicolog\u00eda, Medicina Legal y Forense y Parasitolog\u00eda, Universidad de La Laguna (ULL), 38206 La Laguna, Tenerife, Islas Canarias, Spain"},{"name":"Consorcio Centro de Investigaci\u00f3n Biom\u00e9dica En Red (CIBER) de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, 28006 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ines","family":"Sifaoui","sequence":"additional","affiliation":[{"name":"Instituto Universitario de Enfermedades Tropicales y Salud P\u00fablica de Canarias, Universidad de La Laguna (ULL), Avda. Astrof\u00edsico Fco. S\u00e1nchez, S\/N, 38206 La Laguna, Tenerife, Islas Canarias, Spain"},{"name":"Departamento de Obstetricia y Ginecolog\u00eda, Pediatr\u00eda, Medicina Preventiva y Salud P\u00fablica, Toxicolog\u00eda, Medicina Legal y Forense y Parasitolog\u00eda, Universidad de La Laguna (ULL), 38206 La Laguna, Tenerife, Islas Canarias, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ang\u00e9lica Ribeiro","family":"Soares","sequence":"additional","affiliation":[{"name":"Instituto de Biodiversidade e Sustentabilidade, Universidade Federal do Rio de Janiero, Avda. S\u00e3o Jos\u00e9 do Barreto, 764, Maca\u00e9 27965-045, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8886-7519","authenticated-orcid":false,"given":"Ana R.","family":"D\u00edaz-Marrero","sequence":"additional","affiliation":[{"name":"Instituto Universitario de Bio-Org\u00e1nica Antonio Gonz\u00e1lez (IUBO AG), Universidad de La Laguna (ULL), Avda. Astrof\u00edsico Fco. S\u00e1nchez 2, 38206 La Laguna, Tenerife, Islas Canarias, Spain"},{"name":"Instituto de Productos Naturales y Agrobiolog\u00eda (IPNA), Consejo Superior de Investigaciones Cient\u00edficas (CSIC), Avda. Astrof\u00edsico Fco. S\u00e1nchez 3, 38206 La Laguna, Tenerife, Islas Canarias, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0805-8317","authenticated-orcid":false,"given":"Jos\u00e9 J.","family":"Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Instituto Universitario de Bio-Org\u00e1nica Antonio Gonz\u00e1lez (IUBO AG), Universidad de La Laguna (ULL), Avda. Astrof\u00edsico Fco. S\u00e1nchez 2, 38206 La Laguna, Tenerife, Islas Canarias, Spain"},{"name":"Departamento de Qu\u00edmica Org\u00e1nica, Universidad de La Laguna (ULL), Avda. Astrof\u00edsico Fco. S\u00e1nchez 3, 38206 La Laguna, Tenerife, Islas Canarias, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6233-8224","authenticated-orcid":false,"given":"Jos\u00e9 E.","family":"Pi\u00f1ero","sequence":"additional","affiliation":[{"name":"Instituto Universitario de Enfermedades Tropicales y Salud P\u00fablica de Canarias, Universidad de La Laguna (ULL), Avda. Astrof\u00edsico Fco. 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