Identification of ML251, a Potent Inhibitor of <i>T. brucei and T. cruzi</i> Phosphofructokinase

Human African Trypanosomiasis (HAT) is a severe, often fatal disease caused by the parasitic protist <i>Trypanosoma brucei</i>. The glycolytic pathway has been identified as the sole mechanism for ATP generation in the infective stage of these organisms, and several glycolytic enzymes, phosphofructokinase (PFK) in particular, have shown promise as potential drug targets. Herein, we describe the discovery of <b>ML251</b>, a novel nanomolar inhibitor of <i>T. brucei</i> PFK, and the structure–activity relationships within the series.