2. Academic Validation
  3. Discovery and Optimization of a Compound Series Active against Trypanosoma cruzi, the Causative Agent of Chagas Disease

Discovery and Optimization of a Compound Series Active against Trypanosoma cruzi, the Causative Agent of Chagas Disease

  • J Med Chem. 2020 Mar 26;63(6):3066-3089. doi: 10.1021/acs.jmedchem.9b01852.
Justin R Harrison 1,  Sandipan Sarkar 2,  Shahienaz Hampton 1,  Jennifer Riley 1,  Laste Stojanovski 1,  Christer Sahlberg 3,  Pia Appelqvist 3,  Jessey Erath 4,  Vinodhini Mathan 2,  Ana Rodriguez 4,  Marcel Kaiser 5 6,  Dolores Gonzalez Pacanowska 7,  Kevin D Read 1,  Nils Gunnar Johansson 3,  Ian H Gilbert 1
Affiliations

Affiliations

  • 1 Drug Discovery Unit, Division of Biological Chemistry and Drug Discovery, University of Dundee, Dundee DD1 5EH, United Kingdom.
  • 2 Syngene International Ltd, Biocon Park, SEZ, Bommasandra Industrial Area, Phase-IV, Bommasandra-Jigani Link Road, Bangalore 560 099, India.
  • 3 Medivir, Lunastigen 7, 141 44 Huddinge, Sweden.
  • 4 New York University School of Medicine, 430 East 29th Street, Alexandria Center West Tower, Room 511, Lab 524, New York, New York 10010, United States.
  • 5 Swiss Tropical and Public Health Institute (Swiss TPH), Socinstrasse 57, Basel CH-4051, Switzerland.
  • 6 University of Basel, Petersplatz 1, Basel CH-4003, Switzerland.
  • 7 Instituto de Parasitología y Biomedicina "López-Neyra", Avda. Conocimiento S/N, Parque Tecnológico Ciencias de la Salud18016 Armilla, Granada Spain.
PMID: 32134269 DOI: 10.1021/acs.jmedchem.9b01852
Abstract

Chagas 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.

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