TITLE:
In Vitro Activity of Squaramides and Acyclic Polyamine Derivatives against Trophozoites and Cysts of Acanthamoeba castellanii
AUTHORS:
M. J. Rosales, M. Ximenis, A. Costa, C. Rotger, D. Romero, F. Olmo, E. Delgado, M. P. Clares, E. García-España, C. Marín, M. Sánchez
KEYWORDS:
Acanthamoeba, Squaramides, Acyclic Polyamines, Amoebicidal, Cysticidal
JOURNAL NAME:
Journal of Biosciences and Medicines,
Vol.6 No.8,
August
2,
2018
ABSTRACT: Pathogenic
strains of Acanthamoeba cause
keratitis (AK), granulomatous amoebic encephalitis (GAE), amoebic pneumonitis
(AP), and skin infection in human and animals. The treatment of an Acanthamoeba infection is invariably
very difficult and not always effective, and compounds that are amebicidic or
amebistatic are frequently toxic and/or irritating for humans. Squaramides and
polyamine derivatives have been demonstrated to have antitumor and
antiprotozoal activity. The aim of this study was to investigate the activity
of 5 squaramides and 5 acyclic polyamines against trophozoites and cysts of A. castellanii Neff. Amoebicidal
activity against the trophozoites and cytotoxicity against Vero cells were
evaluated with a colorimetric assay, using Alamar Blue?, and chlorhexidine
digluconate was assayed as the reference drug. The squaramides 3 and 5 and the
acyclic polyamine 6 appeared to be the most active against the trophozoites and
their cytotoxicity was low, showing selectivity indexes of 28.3, 26, and 25.7, respectively,
similar to the control drug, chlorhexidine digluconate (27.6). But only the
squaramide 3 showed complete cysticidal activity at the concentrations of 100
and 200 μM, as the chlorhexidine digluconate. Further studies of the mechanism
of action and in vivo assays are
needed, but squaramide 3 could be used for developing novel therapeutic
approaches against Acanthamoeba infections.