Naegleria fowleriis a
pathogenic
amoeba that causes a fulminant and rapidly progressive disease affecting
the central nervous system called primary amoebic meningoencephalitis
(PAM). Moreover, the disease is fatal in more than 97% of the reported
cases, mostly affecting children and young people after practicing
aquatic activities in nontreated fresh and warm water bodies contaminated
with these amoebae. Currently, the treatment of primary amoebic meningoencephalitis
is based on a combination of different antibiotics and antifungals,
which are not entirely effective and lead to numerous side effects.
In the recent years, research against PAM is focused on the search
of novel, less toxic, and fully effective antiamoebic agents. Previous
studies have reported the activity of cyano-substituted molecules
in different protozoa. Therefore, the activity of 46 novel synthetic
cyanomethyl vinyl ethers (QOET-51 to QOET-96) against two type strains
ofN. fowleri(ATCC 30808 and ATCC
30215) was determined. The data showed that QOET-51, QOET-59, QOET-64,
QOET-67, QOET-72, QOET-77, and QOET-79 were the most active molecules.
In fact, the selectivity index (CC50/IC50) was
sixfold higher when compared to the activities of the drugs of reference.
In addition, the mechanism of action of these compounds was studied,
with the aim to demonstrate the induction of a programmed cell death
process inN. fowleri.