Identification of ML251, a Potent Inhibitor of T. brucei and T. cruzi Phosphofructokinase

ACS Med Chem Lett. 2013 Oct 30;5(1):12-7. doi: 10.1021/ml400259d. eCollection 2014 Jan 9.


Human African Trypanosomiasis (HAT) is a severe, often fatal disease caused by the parasitic protist Trypanosoma brucei. 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 ML251, a novel nanomolar inhibitor of T. brucei PFK, and the structure-activity relationships within the series.

Keywords: Trypanosoma brucei; Trypanosoma cruzi; glycolysis; high-throughput screening; inhibitors; phosphofructokinase.