Open AccessHalogenated tryptophan derivatives disrupt essential transamination mechanisms in bloodstream form Trypanosoma brucei
Author(s) -
Peter E. Cockram,
Emily A. Dickie,
Michael P. Barrett,
Terry Smith
Publication year - 2020
Publication title -
plos neglected tropical diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.99
H-Index - 135
eISSN - 1935-2735
pISSN - 1935-2727
DOI - 10.1371/journal.pntd.0008928
Subject(s) - transamination , trypanosoma brucei , trypanosoma cruzi , amino acid , tryptophan , biology , aromatic amino acids , biochemistry , african trypanosomiasis , virulence , metabolism , trypanosoma , trypanocidal agent , trypanosomiasis , microbiology and biotechnology , parasite hosting , virology , world wide web , computer science , gene
Amino acid metabolism within Trypanosoma brucei , the causative agent of human African trypanosomiasis, is critical for parasite survival and virulence. Of these metabolic processes, the transamination of aromatic amino acids is one of the most important. In this study, a series of halogenated tryptophan analogues were investigated for their anti-parasitic potency. Several of these analogues showed significant trypanocidal activity. Metabolomics analysis of compound-treated parasites revealed key differences occurring within aromatic amino acid metabolism, particularly within the widely reported and essential transamination processes of this parasite.