ArticleParasitology international2013
Membrane active chelators as novel anti-African trypanosome and anti-malarial drugs.
Article in Parasitology international, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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6 authors at 2 institutions in 1 country.
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Abstract
Malaria (Plasmodium spp.) and human African trypanosomiasis (Trypanosoma brucei spp.) are vector borne, deadly parasitic diseases. While chemotherapeutic agents for both diseases are available, difficulty in disease eradication and development of drug resistance require that new therapies targeting unexplored pathways or exploiting novel modes of action be developed. Intracellular Plasmodium and extracellular Trypanosoma brucei may have unique and essential requirements for divalent metal ions, beyond that deemed physiological for the host. Membrane Active Chelators (MACs), biologically active only in a hydrophobic lipid environment, are able to bind metal ions at elevated non-physiological concentrations in the vicinity of cell membranes. A dose-response relationship study using validated viability assays revealed that two MAC drugs, DP-b99 and DP-460, were cytotoxic for these parasites in vitro. The 50% effective concentration (EC50) values for DP-b99 and DP-460 were 87 μM and 39 μM for Trypanosoma brucei brucei and 21 μM and 28 μM for erythrocytic Plasmodium falciparum, respectively. Furthermore, drug potency was maintained for at least 24h in serum containing medium at 37°C. While the exact mechanism of action of MACs against intracellular malaria and extracellular African trypanosome parasites has yet to be determined, their potential as antiparasitic agents warrants further investigation.
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