Current medicines hold promise in the treatment of orphan infections due to brain-eating amoebae

Figures & data

Figure 1. Central nervous system infections due to brain-eating amoebae are challenging to treat with extremely poor prognosis. Re-purposing clinically used drugs for neuropathological conditions that are blood-brain barrier permeable, as well as parasite-specific compounds developed against related protozoa are potential avenues to design chemotherapeutics against orphan infections due to pathogenic free-living amoebae.

Table 1. List of compounds targeting ergosterol

Drug/Compound	Chemical Structure	Function
Clinically-used drugs against neuropathological conditions
Diazepam		Anti-seizure and for anxiety disorder.
Phenobarbitone		Anti-epileptic properties.
Phenytoin		Anti-seizure effects.
Drugs with known anti-protozoal (Entamoeba) activity
2-Acetylpyridine dithiocarbazates	2-acetylpyridine Dithiocarbazates	Target metal-dependent and sulfhydryl enzyme systems in fungi, bacteria, plants, and insects, as well as mammals.
Anemonin		Inhibits the transcription of the genes encoding MITF, TYR, TRP1, and TRP2.
Apigenin		Induces mitochondrial death cascade by inhibition of VEGF and HIF-1 expression via pI3K/AKT/p70S6K1 and HDM2/p53 pathways.
Aromoline		Alkaloid with anti-neuroprotective properties.
Berberine		Alkaloid with anti-neuropathological effects.
Conessine		High blood-brain barrier penetration and high affinity for the adrenergic receptors.
Cryptopleurine		Protein synthesis inhibitor, an antineoplastic agent, and an antiviral agent.
Emetine		Protein synthesis inhibitor in eukaryotic cells.
Glaucarubin		An anti-Entamoeba agent and is found to be cytotoxic. It may be of use in cancer chemotherapy.
Gossypol		An inhibitor for several dehydrogenase enzymes.
Insularine		Anxiety-like Behavior.
Isotrilobine		Inhibits hepatocellular carcinoma.
Kaempferol		Triggers apoptosis, cell cycle arrest at G2/M phase, downregulation of signaling pathways, and phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT).
Luteolin		Binds to the thromboxane A2 receptor and inhibits vascular endothelial growth factor-induced angiogenesis by targeting PI3K activity.
Quassin		Properties include insecticidal, herbicidal, anti-parasitic, antimalarial, and anticancer.
Mangostin		Anti-inflammatory effects.
Marmelosin		Potential inhibitor of Acetyl- and Butyrylcholinesterase.
Matrine		Inhibition of cell proliferation and induction of apoptosis.
Minecoside		Minecoside is a hydroxycinnamic acid.
Specioside		Anti-inflammatory and anti-neoplastic properties.
Thiosemicarbazone		Antiproliferative properties.
1,2,4- Triazine		Herbicide/oxidative stress.
Triterpene		Anticancer activities.
Usambarensine		Induces apoptosis.
Verminoside		Anti-inflammatory and anti-neoplastic properties.
Drug repurposing library
Acriflavine		Antibacterial properties.
AR-42 (also known as ‘(S)-N-Hydroxy-4-(3-methyl-2-phenylbutanamido)benzamide’)		Anti-tumor effects mainly by upregulating the expression of p21 and blocking the transduction of multiple signaling cascades related to tumor growth.
Bardoxolone		Anti-inflammatory effects, inhibition of nuclear factor κB (NF-κB), and decreased oxidative stress.
BC-3205		Antibacterial effects.
BPH-942		Antiestrogenic effect.
Dacinostat		Potential anticancer activity.
Fimepinostat		Inhibitor of HDAC and PI3K.
Fumagillin		Angiogenesis inhibitor in the treatment of cancer.
Halofuginone		Binding to glutamyl-prolyl-tRNA synthetase (EPRS) and inhibiting prolyl-tRNA synthetase activity.
Nitracrine		Anti-eukaryotic and Antiviral Compounds.
NVP-HSP990		HSP90 inhibitor.
Omipalisib		Inducing apoptotic cell death.
Pabinostat		Inhibits cellular differentiation and cell-cycle progression.
Pelitrexol		Phosphoribosylglycinamide formyltransferase inhibitors.
PF-4287881		Also known as PF-04,287,881. A ketolide antimicrobial agent under clinical development.
Pracinostat		Anti-tumor activities and induction of apoptosis.
Quisinostat		Anti-tumor activities and induction of apoptosis.
Radicicol		Suppresses oncogene-induced transformation of NIH 3T3 cells and it also selectively disrupts the K-Ras-activated signaling pathways.
Sanguinarine		Antibacterial effects.
Solithromycin		Antimicrobial properties by binding to the large 50S subunit of the ribosome and inhibits protein biosynthesis.