Discovery of 2-(1H-imidazo-2-yl)piperazines as a new class of potent and non-cytotoxic inhibitors of Trypanosoma brucei growth in vitro |
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Authors: | Federica Ferrigno Ilaria Biancofiore Savina Malancona Simona Ponzi Giacomo Paonessa Rita Graziani Alberto Bresciani Nadia Gennari Annalise Di Marco Marcel Kaiser Vincenzo Summa Steven Harper Jesus M Ontoria |
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Institution: | 1. Departments of Chemistry and Biology, IRBM Science Park, Via Pontina km 30,600, 00071 Pomezia, Rome, Italy;2. Swiss Tropical and Public Health Institute, Socinstrasse 57, 4051 Basel, Switzerland;3. University of Basel, Petersplatz 1, 4003 Basel, Switzerland |
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Abstract: | The identification of a new series of growth inhibitors of Trypanosoma brucei rhodesiense, causative agent of Human African Trypanosomiasis (HAT), is described. A selection of compounds from our in-house compound collection was screened in vitro against the parasite leading to the identification of compounds with nanomolar inhibition of T. brucei growth. Preliminary SAR on the hit compound led to the identification of compound 34 that shows low nanomolar parasite growth inhibition (T. brucei EC50 5?nM), is not cytotoxic (HeLa CC50?>?25,000?nM) and is selective over other parasites, such as Trypanosoma cruzi and Plasmodium falciparum (T. cruzi EC50 8120?nM, P. falciparum EC50 3624?nM). |
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Keywords: | Sleeping sickness Human African Trypanosomiasis (HAT) Antiparasitic Corresponding author |
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