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Title

Antiamoeboid activity of squamins C–F, cyclooctapeptides from Annona globifora

AuthorsRodríguez-Expósito, Rubén L.; Sosa-Rueda, Javier; Reyes-Batlle, María; Sifaoui, Inés; Cen-Pacheco, Francisco; Hernández Daranas, Antonio CSIC ORCID ; Díaz-Marrero, Ana R. CSIC ORCID; Piñero, José E.; Fernández, José J.; Lorenzo-Morales, Jacob
KeywordsSquamin
Cyclopeptide
Acanthamoeba
Annona
Antiamoeboid
Issue Date9-Dec-2021
PublisherElsevier
Australian Society for Parasitology
CitationInternational Journal for Parasitology: Drugs and Drug Resistance 17: 67-79 (2021)
AbstractFree-living amoebae of Acanthamoeba spp. are causative agents of human infections such as granulomatous amoebic encephalitis (GAE) and Acanthamoeba keratitis (AK). The exploration of innovative chemical entities from natural sources that induce intrinsic apoptotic pathway or a Programmed Cell Death (PCD) in Acanthamoeba protozoa is essential to develop new therapeutic strategies. In this work, the antiamoeboid activity of squamins C–F (1–4), four cyclooctapeptides isolated from Annona globiflora was tested in vitro against Acanthamoeba castellanii Neff, A. polyphaga, A. quina, and A. griffini, and a structure–activity relationship was also established. The most sensitive strain against all tested cyclooctapeptides was A. castellanii Neff being the R conformers of the S-oxo-methionine residue, squamins D (2) and F (4), the most active against the trophozoite stage. It is remarkable that all four peptides showed no cytotoxic effects against murine macrophages cell line J774A.1. The analysis of the mode of action of squamins C–F against A. castellanii indicate that these cyclopeptides induced the mechanisms of programmed cell death (PCD). All peptides trigger mitochondrial damages, significant inhibition of ATP production compared to the negative control, chromatin condensation and slight damages in membrane that affects its permeability despite it conserves integrity at the IC90 for 24 h. An increase in reactive oxygen species (ROS) was observed in all cases.
Publisher version (URL)https://doi.org/10.1016/j.ijpddr.2021.08.003
URIhttp://hdl.handle.net/10261/255621
DOI10.1016/j.ijpddr.2021.08.003
ISSN2211-3207
Appears in Collections:(IPNA) Artículos

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