jm9b01852_si_001.pdf (844.74 kB)
Discovery and Optimization of a Compound Series Active against Trypanosoma cruzi, the Causative Agent of Chagas Disease
journal contribution
posted on 2020-03-05, 14:32 authored by Justin
R. Harrison, Sandipan Sarkar, Shahienaz Hampton, Jennifer Riley, Laste Stojanovski, Christer Sahlberg, Pia Appelqvist, Jessey Erath, Vinodhini Mathan, Ana Rodriguez, Marcel Kaiser, Dolores Gonzalez Pacanowska, Kevin D. Read, Nils Gunnar Johansson, Ian H. GilbertChagas disease is
caused by the protozoan parasite Trypanosoma
cruzi. It is endemic in South and Central America and recently
has been found in other parts of the world, due to migration of chronically
infected patients. The current treatment for Chagas disease is not
satisfactory, and there is a need for new treatments. In this work,
we describe the optimization of a hit compound resulting from the
phenotypic screen of a library of compounds against T. cruzi. The compound series was optimized to the level where it had satisfactory
pharmacokinetics to allow an efficacy study in a mouse model of Chagas
disease. We were able to demonstrate efficacy in this model, although
further work is required to improve the potency and selectivity of
this series.