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The adhesion to extracellular matrix (ECM) proteins is considered as one of the key steps in the success of the infection and could represent an interesting target to be explored in the prevention and treatment of the disease. In this work, the effect of two sesquiterpenes with proven anti-Naegleria activity on the adhesion of the parasite was evaluated using an in vitro ECM-based model, compared with the reference drugs amphotericin B and staurosporine. Both laurinterol and (+)-elatol inhibited the adhesion of the N. fowleri trophozoites to the main proteins of the ECM when treating them at different concentrations and exposure times. This work not only reinforces the therapeutic potential of laurinterol and (+)-elatol against N. fowleri infection but also introduces the application of ECM-based adhesion assays as a novel and valuable tool for screening candidate compounds that disrupt host\u2013pathogen interactions critical to PAM pathogenesis.<\/jats:p>","DOI":"10.3390\/md23080306","type":"journal-article","created":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T07:37:23Z","timestamp":1753861043000},"page":"306","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Potential Inhibitors of Human\u2013Naegleria fowleri Interactions: An In Vitro Extracellular Matrix-Based Model"],"prefix":"10.3390","volume":"23","author":[{"given":"Javier","family":"Chao-Pellicer","sequence":"first","affiliation":[{"name":"Instituto Universitario de Enfermedades Tropicales y Salud P\u00fablica de Canarias, Universidad de La Laguna, Avda. Astrof\u00edsico Fco. S\u00e1nchez, S\/N, 38203 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, 38200 La laguna, Tenerife, Islas Canarias, Spain"},{"name":"CIBER de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I\u00f1igo","family":"Arberas-Jim\u00e9nez","sequence":"additional","affiliation":[{"name":"Instituto Universitario de Enfermedades Tropicales y Salud P\u00fablica de Canarias, Universidad de La Laguna, Avda. Astrof\u00edsico Fco. S\u00e1nchez, S\/N, 38203 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, 38200 La laguna, Tenerife, Islas Canarias, 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, Avda. Astrof\u00edsico Fco. 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