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

By Ferrigno, Federica; Biancofiore, Ilaria; Malancona, Savina; Ponzi, Simona; Paonessa, Giacomo; Graziani, Rita; Bresciani, Alberto; Gennari, Nadia; Di Marco, Annalise; Kaiser, Marcel; et al
From Bioorganic & Medicinal Chemistry Letters (2018), 28(23-24), 3689-3692. Language: English, Database: CAPLUS, DOI:10.1016/j.bmcl.2018.10.028

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 compds. from our inhouse compd. collection was screened in vitro against the parasite leading to the identification of compds. with nanomolar inhibition of T. brucei growth. Preliminary SAR on the hit compd. led to the identification of compd. 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).