Background: Amiodarone is prescribed for certain cardiac arrhythmias in
current medical practice. The drug targets and inhibits voltage dependent sodium
v), calcium (Ca+2
v), potassium (K+
v) channels, enzymes like cytochrome P450
and oxidosqualene cyclase. Past studies have shown that amiodarone exerts antiparasitic
effects against Trypanosoma cruzi and Acanthamoeba castellanii.
Objectives: The presence of aforementioned targets and the type of cell death induced
by amiodarone in pathogenic eukaryotes like Acanthamoeba castellanii remains
to be established. We inferred the presence of homologous targets of amiodarone
in A. castellanii compared with humans.
Methods: This study used bioinformatics exploration for amino acid sequence homology,
ligand binding attribute predictions, 3D structural model development, and
experimental assays that highlight similarity between certain target proteins in Acanthamoeba
as compared to humans.
Results: The sequence identity scores for amino acids and 3D models show that A. castellanii
expresses similar types of targets of amiodarone like Na+
v - K+1
v channels, cytochrome
P450 3A4, and lanosterol synthase (oxidosqualene cyclase). We show that even
though human like L-type and two pore Ca+2 channels are present in A. castellanii, there
was no evidence of the expression of T-type voltage dependent Ca+2 channels. Growth
assays showed amoebicidal and amoebistatic effects at doses of 40-80μg/ml.
Conclusion: The existing bioinformatics tools, ligand binding attribute prediction,
and model building offer a specific method to establish homology of proteins, discover
drug targets, and facilitate the investigation of the evolution of several types of
cardinal ion channels from unicellular eukaryotes to multicellular species as humans.