1. Abdul Mannan Baig* et al.
Evidence of the Targets of Amiodarone in Acanthamoeba spp. Bioinformatics and experimentations.
Abdul Mannan Baig* et al.
* Department of Biological and Biomedical Sciences, Aga Khan University, Karachi, Pakistan
Introduction
Ion channels coupled to cell membrane receptors are seen in many multicellular eukaryotes to execute several metabolic and survival functions. Their role in the biology of the unicellular pathogenic eukaryotes, like Naegleria fowleri and Acanthamoeba specie [Fig.1] has emerged recently
Results
Results Contd…
Fig. 4 Effects of different doses of Amiodarone on A.castellanii. (B) Control vs (E-F) 60 and 80µg/ml of Amiodarone.
Fig. 2 Homology of Acanthamoeba ACA1_ K+ channel protein human Potassium voltage-gated channel IKr Protein
We found structural homology and ligand binding similarities between ACA1_ K+ channel protein human Potassium voltage-gated channel IKr Protein [Fig.1], human voltage gated Na Channel (NavCt) and ACA1_ t26_1of Acanthamoeba [ Fig.2] as well as Lanosterol synthase [Fig.3]. Experiments show that 60 and 80µg/ml of Amiodarone had significant amoebicidal effects (P < 0.001) [Fig.4].
Human voltage gated Na Channel (NavCt) and NavCt play an important role in excitable cells like neurons and cardiac tissues (1). Similar channels in Acanthamoeba could plays vital roles in mobility and cell division. Amiodarone targeting these proteins could prove lethal for trophozoites, as seen in this study. Additionally Lanosterol synthase targeting (2) by amiodarone contributes toward the kill effects seen with this drug.
Fig. 1. Acanthamoeba castellanii
Results and Discussion
Aim
Amiodarone, that binds K+ ion channels is being reported to be amoebicidal in pathogenic eukaryotes; therefore we hypothesized the presence of a homologous targets in Acanthamoeba spp. 
Methodology
Searches were made for finding the homology of the amino acid sequence of potassium voltage-gated channel subfamily H member 2,  voltage-dependent T-type calcium channel subunit alpha-1H, voltage-dependent calcium channel subunit alpha-2/delta-2, Beta-1 adrenergic receptor and group of enzymes like cytochrome P450 and oxidosqualene cyclase, searches were done at the Acanthamoeba genomic and protein databases at Uniprot, NCBI and Amoebadb.org.
Fig. 3 Homology of human voltage gated Na Channel (NavCt) and ACA1_ t26_1of Acanthamoeba
References
Cohen CJ, Spires S, Van Skiver D: Block of T-type Ca channels in guinea pig atrial cells by anti-arrhythmic agents and Ca channel antagonists. J Gen Physiol Oct;100(4):
Benaim G, et al., Amiodarone has intrinsic anti-Trypanosoma cruzi activity and acts synergistically with posaconazole. J Med Chem Feb 9;49(3):892-9.
Fig. 3 Lanosterol Synthase as a target of Amiodarone