Design, synthesis and evaluation of tryptophan analogues as tool compounds to study IDO1 activity

We report the rational design, novel syntheses and biophysical and in silico evaluation of tryptophan-inspired tool compounds to probe the illusive MOA of the clinically-relevant heme-dioxygenase protein, IDO1.

Halogenated tryptophan derivatives disrupt essential transamination mechanisms in bloodstream form Trypanosoma brucei

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.