Trypanothione reductase high-throughput screening campaign identifies novel classes of inhibitors with anti-parasitic activity

A high-throughput screening campaign of 100,000 lead like compounds led to the identification of 9 novel chemical classes of trypanothione reductase (TR) inhibitors worthy of further investigation. Hits from 5 of these chemical classes have been developed further through different combinations of preliminary SAR probing, anti-parasitic, cytotoxicity, and assessment of their chemical and in vitro metabolic properties. This has led to the identification of novel TR inhibitor chemotypes that are drug like and display anti-parasitic activity. For one class a series of analogues have displayed a correlation between TR inhibition and anti-parasitic activity. This paper explores the process of identifying, investigating and evaluating a series of hits from a high-throughput screening campaign.