High-throughput screening affords novel and selective trypanothione reductase inhibitors with anti-trypanosomal activity

Trypanothione reductase (TR), an enzyme that buffers oxidative stress in trypanosomatid parasites, was screened against commercial libraries containing approximately 134,500 compounds. After secondary screening, four chemotypes were identified as screening positives with selectivity for TR over human glutathione reductase. Thirteen compounds from these four chemotypes were purchased, and their in vitro activity against TR and Trypanosoma brucei is described.

Graphical abstractTrypanothione reductase (TR) was screened against 134,500 compounds. Four chemotypes were selective for TR over human glutathione reductase. The in vitro activity of 13 purchased compounds against TR and Trypanosoma brucei is summarized.Figure optionsDownload full-size imageDownload as PowerPoint slide