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Discovery of 2-(1H-imidazo-2-yl)piperazines as a new class of potent and non-cytotoxic inhibitors of Trypanosoma brucei growth in vitro.
- Source :
-
Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2018 Dec 15; Vol. 28 (23-24), pp. 3689-3692. Date of Electronic Publication: 2018 Oct 22. - Publication Year :
- 2018
-
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 EC <subscript>50</subscript> 5 nM), is not cytotoxic (HeLa CC <subscript>50</subscript> > 25,000 nM) and is selective over other parasites, such as Trypanosoma cruzi and Plasmodium falciparum (T. cruzi EC <subscript>50</subscript> 8120 nM, P. falciparum EC <subscript>50</subscript> 3624 nM).<br /> (Copyright © 2018 Elsevier Ltd. All rights reserved.)
- Subjects :
- HeLa Cells
Humans
Imidazoles chemistry
Imidazoles pharmacology
Malaria, Falciparum drug therapy
Plasmodium falciparum drug effects
Structure-Activity Relationship
Trypanosoma brucei brucei growth & development
Trypanosomiasis, African parasitology
Piperazines chemistry
Piperazines pharmacology
Trypanocidal Agents chemistry
Trypanocidal Agents pharmacology
Trypanosoma brucei brucei drug effects
Trypanosomiasis, African drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1464-3405
- Volume :
- 28
- Issue :
- 23-24
- Database :
- MEDLINE
- Journal :
- Bioorganic & medicinal chemistry letters
- Publication Type :
- Academic Journal
- Accession number :
- 30482621
- Full Text :
- https://doi.org/10.1016/j.bmcl.2018.10.028