Optimising inhibitors of trypanothione reductase using solid-phase chemistry

A series of inhibitors of the enzyme trypanothione reductase has been identified using directed solid-phase chemistry. The compounds were based on a series of polyamine scaffolds and used the natural product kukoamine A as the lead structure. A compound with a Ki of 76 nM was identified, although somewhat surprisingly the compound appeared to be noncompetitive in nature.