Abstract
Naegleria fowleri (N. fowleri)
is a free-living, unicellular, opportunistic protist responsible for the fatal central nervous system infection, primary amoebic meningoencephalitis (PAM). Given the increase in temperatures due to global warming and climate change, it is estimated that the cases of PAM are on the rise. However, there is a current lack of awareness and effective drugs, meaning there is an urgent need to develop new therapeutic drugs. In this study, the target compounds were synthesized and tested for their anti-amoebic properties against
N. fowleri.
Most compounds exhibited significant amoebicidal effects against
N. fowleri
; for example,
1h
,
1j
, and
1q
reduced
N. fowleri’s
viability to 15.14%, 17.45% and 28.78%, respectively. Furthermore, the majority of the compounds showed reductions in amoeba-mediated host death. Of interest are the compounds
1f
,
1k
, and
1v
, as they were capable of reducing the amoeba-mediated host cell death to 52.3%, 51%, and 56.9% from 100%, respectively. Additionally, these compounds exhibit amoebicidal properties as well; they were found to decrease
N. fowleri’s
viability to 26.41%, 27.39%, and 24.13% from 100%, respectively. Moreover, the MIC
50
values for
1e
,
1f
, and
1h
were determined to be 48.45 µM, 60.87 µM, and 50.96 µM, respectively. Additionally, the majority of compounds were found to exhibit limited cytotoxicity, except for
1l
,
1o
,
1p
,
1m
,
1c
,
1b
,
1zb
,
1z
,
1y
, and
1x
, which exhibited negligible toxicity. It is anticipated that these compounds may be developed further as effective treatments against these devastating infections due to brain-eating amoebae.