Inhibition of L-Threonine Dehydrogenase from Trypanosoma cruzi reduces glycine and acetate production and interferes with parasite growth and viability.

Trypanosoma cruzi is a flagellated protozoan and the etiological agent of Chagas Disease, a neglected tropical disease described by Carlos Chagas in 1909 that remains without appropriate diagnostics and treatment. Throughout its life cycle, T. cruzi undergoes through many different environments, requiring adaptation of its metabolism to different nutrition sources.

Malic Enzyme Is the Target for Sulfonamide Hits from the GSK Chagas Box.

Chagas disease, an infectious condition caused by , lacks treatment with drugs with desired efficacy and safety profiles. To address this unmet medical need, a set of trypanocidal compounds were identified through a large multicenter phenotypic-screening initiative and assembled in the GSK Chagas Box. In the present work, we report the screening of the Chagas Box against malic enzymes (MEs) and the identification of three potent inhibitors of its cytosolic isoform (TcMEc).

In Vitro Image-Based Assay for Trypanosoma cruzi Intracellular Forms.

The advances in development and popularization of automated fluorescence microscopes and pipetting robots allowed scientists to establish high-throughput compound screening using image-based assays for Trypanosoma cruzi intracellular forms, which are associated to chronic Chagas disease. An intracellular T. cruzi image-based assay is a valuable tool to early stage drug discovery for Chagas disease, because it allows scientists to assess a compound's efficacy and safety in the same experiment.

Discovery of Potent -Ethylurea Pyrazole Derivatives as Dual Inhibitors of and .

() and () are causative agents of parasitic diseases known as human African trypanosomiasis and Chagas disease, respectively. Together, these diseases affect 68 million people around the world. Current treatments are unsatisfactory, frequently associated with intolerable side-effects, and generally inadequate in treating all stages of disease.