2. Academic Validation
  3. Discovery of 2-(1H-imidazo-2-yl)piperazines as a new class of potent and non-cytotoxic inhibitors of Trypanosoma brucei growth in vitro

Discovery of 2-(1H-imidazo-2-yl)piperazines as a new class of potent and non-cytotoxic inhibitors of Trypanosoma brucei growth in vitro

  • Bioorg Med Chem Lett. 2018 Dec 15;28(23-24):3689-3692. doi: 10.1016/j.bmcl.2018.10.028.
Federica Ferrigno 1,  Ilaria Biancofiore 2,  Savina Malancona 2,  Simona Ponzi 2,  Giacomo Paonessa 2,  Rita Graziani 2,  Alberto Bresciani 2,  Nadia Gennari 2,  Annalise Di Marco 2,  Marcel Kaiser 3,  Vincenzo Summa 2,  Steven Harper 2,  Jesus M Ontoria 2
Affiliations

Affiliations

  • 1 Departments of Chemistry and Biology, IRBM Science Park, Via Pontina km 30,600, 00071 Pomezia, Rome, Italy. Electronic address: [email protected].
  • 2 Departments of Chemistry and Biology, IRBM Science Park, Via Pontina km 30,600, 00071 Pomezia, Rome, Italy.
  • 3 Swiss Tropical and Public Health Institute, Socinstrasse 57, 4051 Basel, Switzerland; University of Basel, Petersplatz 1, 4003 Basel, Switzerland.
PMID: 30482621 DOI: 10.1016/j.bmcl.2018.10.028
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).

Keywords

2-(1H-imidazo-2-yl)piperazines; Antiparasitic; Human African Trypanosomiasis (HAT); Sleeping sickness; Trypanosoma brucei.

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