Abstract
In tropical regions, protozoan parasites can cause severe diseases with malaria, leishmaniasis, sleeping sickness, and Chagas disease standing in the forefront. Many of the drugs currently being used to treat these diseases have been developed more than 50 years ago and can cause severe adverse effects. Above all, resistance to existing drugs is widespread and has become a serious problem threatening the success of control measures. In order to identify new antiprotozoal agents, more than 600 commercial agrochemicals have been tested on the pathogens causing the above mentioned diseases. For all of the pathogens, compounds were identified with similar or even higher activities than the currently used drugs in applied in vitro assays. Furthermore, in vivo activity was observed for the fungicide/oomyceticide azoxystrobin, and the insecticide hydramethylnon in the Plasmodium berghei mouse model, and for the oomyceticide zoxamide in the Trypanosoma brucei rhodesiense STIB900 mouse model, respectively.
Highlights
The Protozoan parasites of the genera Plasmodium spp., Leishmania spp., Trypanosoma brucei spp. and Trypanosoma cruzi, are the disease causative agents threatening entire populations in mainly resource poor countries around the world.Malaria, due to infection with Plasmodium spp., is one of the most devastating diseases in developing countries, with 216 million cases in 2010, causing an estimated 655,000 deaths per year [1]
Starting with the analysis of the phylogenetic relationship of the pests combated with agrochemicals, and the most important tropical infectious disease pathogens as defined by WHO [36], the close relationship of oomycetes, to which important agricultural pathogens like potato blight or downy mildew belong, with protozoan parasites was realized [37]
Over 600 commercially available agrochemicals were selected and their activity against the tropical disease pathogens Plasmodium falciparum, Leishmania donovani, Trypanosoma cruzi and Trypanosoma brucei rhodensiense tested in cell based screens
Summary
The Protozoan parasites of the genera Plasmodium spp., Leishmania spp., Trypanosoma brucei spp. and Trypanosoma cruzi, are the disease causative agents threatening entire populations in mainly resource poor countries around the world. Due to infection with Plasmodium spp., is one of the most devastating diseases in developing countries, with 216 million cases in 2010, causing an estimated 655,000 deaths per year [1]. Other recent estimates assume up to 1.2 million deaths per year [2]. Large libraries from pharma companies have been screened against protozoan parasites and some interesting hits [4,5,6,7] have been found, especially against malaria with the spiroindolones currently undergoing clinical evaluation [8,9]
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