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

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

  • Harrison JR Drug Discovery Unit, Division of Biological Chemistry and Drug Discovery, University of Dundee, Dundee DD1 5EH, United Kingdom.
  • Sarkar S Syngene International Ltd, Biocon Park, SEZ, Bommasandra Industrial Area, Phase-IV, Bommasandra-Jigani Link Road, Bangalore 560 099, India.
  • Hampton S Drug Discovery Unit, Division of Biological Chemistry and Drug Discovery, University of Dundee, Dundee DD1 5EH, United Kingdom.
  • Riley J Drug Discovery Unit, Division of Biological Chemistry and Drug Discovery, University of Dundee, Dundee DD1 5EH, United Kingdom.
  • Stojanovski L Drug Discovery Unit, Division of Biological Chemistry and Drug Discovery, University of Dundee, Dundee DD1 5EH, United Kingdom.
  • Sahlberg C Medivir, Lunastigen 7, 141 44 Huddinge, Sweden.
  • Appelqvist P Medivir, Lunastigen 7, 141 44 Huddinge, Sweden.
  • Erath J 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.
  • Mathan V Syngene International Ltd, Biocon Park, SEZ, Bommasandra Industrial Area, Phase-IV, Bommasandra-Jigani Link Road, Bangalore 560 099, India.
  • Rodriguez A 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.
  • Kaiser M Swiss Tropical and Public Health Institute (Swiss TPH), Socinstrasse 57, Basel CH-4051, Switzerland.
  • Pacanowska DG Instituto de Parasitología y Biomedicina "López-Neyra", Avda. Conocimiento S/N, Parque Tecnológico Ciencias de la Salud18016 Armilla, Granada Spain.
  • Read KD Drug Discovery Unit, Division of Biological Chemistry and Drug Discovery, University of Dundee, Dundee DD1 5EH, United Kingdom.
  • Johansson NG Medivir, Lunastigen 7, 141 44 Huddinge, Sweden.
  • Gilbert IH Drug Discovery Unit, Division of Biological Chemistry and Drug Discovery, University of Dundee, Dundee DD1 5EH, United Kingdom.
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  • 2020-03-06
Published in:
  • Journal of medicinal chemistry. - 2020
Animals
Cell Line
Chagas Disease
Drug Discovery
Female
Mice, Inbred BALB C
Molecular Structure
Parasitic Sensitivity Tests
Proof of Concept Study
Quinazolinones
Rats
Small Molecule Libraries
Structure-Activity Relationship
Trypanocidal Agents
Trypanosoma cruzi
English 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.
Language
  • English
Open access status
closed
Identifiers
Persistent URL
https://sonar.ch/global/documents/114658
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