ml400259d_si_001.pdf (568.64 kB)
Identification of ML251, a Potent Inhibitor of T. brucei and T. cruzi Phosphofructokinase
journal contribution
posted on 2014-01-09, 00:00 authored by Kyle R. Brimacombe, Martin J. Walsh, Li Liu, Montserrat
G. Vásquez-Valdivieso, Hugh P. Morgan, Iain McNae, Linda A. Fothergill-Gilmore, Paul A. M. Michels, Douglas S. Auld, Anton Simeonov, Malcolm D. Walkinshaw, Min Shen, Matthew B. BoxerHuman 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.