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Bistacrines as potential antitrypanosomal agents

Human African Trypanosomiasis (HAT) is caused by two subspecies of the genus Trypanosoma, namely Trypanosoma brucei rhodesiense and Trypanosoma brucei gambiense. The disease is fatal if left untreated and therapy is limited due to only five non-adequate drugs currently available. In preliminary stud...

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Main Authors: Schmidt, Ines (Author) , Göllner, Sarah (Author) , Miliu, Alexandra (Author) , Krauth-Siegel, Renate (Author)
Format: Article (Journal)
Language:English
Published: 1 July 2017
In: Bioorganic & medicinal chemistry
Year: 2017, Volume: 25, Issue: 16, Pages: 4526-4531
ISSN:1464-3391
DOI:10.1016/j.bmc.2017.06.051
Online Access:Verlag, Volltext: http://dx.doi.org/10.1016/j.bmc.2017.06.051
Verlag, Volltext: http://www.sciencedirect.com/science/article/pii/S0968089617302262
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Author Notes:Ines Schmidt, Sarah Göllner, Antje Fuß, August Stich, Anna Kucharski, Tanja Schirmeister, Elena Katzowitsch, Heike Bruhn, Alexandra Miliu, R. Luise Krauth-Siegel, Ulrike Holzgrabe
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Summary:Human African Trypanosomiasis (HAT) is caused by two subspecies of the genus Trypanosoma, namely Trypanosoma brucei rhodesiense and Trypanosoma brucei gambiense. The disease is fatal if left untreated and therapy is limited due to only five non-adequate drugs currently available. In preliminary studies, dimeric tacrine derivatives were found to inhibit parasite growth with IC50-values in the nanomolar concentration range. This prompted the synthesis of a small, but smart library of monomeric and dimeric tacrine-type compounds and their evaluation of antiprotozoal activity. Rhodesain, a lysosomal cathepsin-L like cysteine protease of T. brucei rhodesiense is essential for parasite survival and likely target of the tacrine derivatives. In addition, the inhibition of trypanothione reductase by bistacrines was found. This flavoprotein oxidoreductase is the main defense against oxidative stress in the thiol redox system unique for protozoa.
Item Description:Gesehen am 23.05.2018
Physical Description:Online Resource
ISSN:1464-3391
DOI:10.1016/j.bmc.2017.06.051

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