Acanthamoeba spp. can cause a sight threatening disease. At present, the current treatments used to treat Acanthamoeba spp. Infections, such as biguanide-based antimicrobials, remain inefficacious, with the appearance of resistant forms and high cytotoxicity to host cells. In this study, an initial screening was conducted against Acanthamoeba castellanii Neff and murine macrophages J774A.1 using alamarBlueTM. Among the 160 compounds included in the cited box, 90% exhibited an inhibition of the parasite above 80%, while only 18.75% of the compounds inhibited the parasite with a lethality towards murine macrophage lower than 20%. Based on the amoebicidal activity, the cytotoxicity assay, and availability, Terconazole was chosen for the elucidation of the action mode in two clinical strains, Acanthamoeba culbertsoni and Acanthamoeba castellanii L10. A fluorescence image-based system and proteomic techniques were used to investigate the effect of the present azole on the cytoskeleton network and various programmed cell death features, including chromatin condensation and mitochondria dysfunction. Taking all the results together, we can suggest that Terconazole can induce programmed cell death (PCD) via the inhibition of sterol biosynthesis inhibition.

Consorcio Centro de Investigación on Biomédica En Red Instituto de Salud Carlos 3 28220 Madrid Spain

Departamento de Obstetricia y Ginecología Pediatría Medicina Preventiva y Salud Pública Toxicología Medicina Legal y Forense y Parasitología Universidad de La Laguna 38200 San Cristóbal de La Laguna Spain

Department of Parasitology Faculty of Science Charles University BIOCEV 252 50 Vestec Czech Republic

Instituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias Avda Astrofísico Fco Sánchez S N 38200 San Cristóbal de La Laguna Spain

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