Wednesday, July 23, 2014

Repurposing the Open Access Malaria Box to discover potent inhibitors of Toxoplasma gondii and Entamoeba histolytica

2014 Jul 21. pii: AAC.02541-14. [Epub ahead of print]
Toxoplasmosis and amoebiasis are important public health concerns worldwide. Currently available drugs to control these diseases have proven their limitations. Therefore, innovative approaches should be adopted to identify and develop new leads from novel scaffolds exhibiting novel modes of actions. This paper describes results from the screening of Medicines for Malaria Venture's Open Access Malaria Box compounds in a search for new anti-Toxoplasma and anti-Entamoeba agents. Standard in vitro phenotypic screening procedures were adopted to assess the biological activities. Seven anti-Toxoplasma hits with IC50 < 5μM and selectivity indexes (SI) greater than 6 were identified. The most interesting hit compound was MMV007791, a piperazinacetamide, with an IC50 of 0.19 μM and a Selectivity Index greater than 157. Also, two compounds MMV666600 and MMV006861 were identified with modest activity against E. histolytica with IC50 values of 10.66 μM and 15.58 μM respectively. The anti-Toxoplasma hits identified in this study belong to different scaffold types than currently used drugs, underscoring their novelty and potential as starting points for the development of new anti-toxoplasmosis drugs with novel modes of action.
Copyright © 2014, American Society for Microbiology. All Rights Reserved.
[PubMed - as supplied by publisher]

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