Novel drug discovery for Chagas disease

Expert Opin Drug Discov. 2016;11(5):447-55. doi: 10.1517/17460441.2016.1160883. Epub 2016 Apr 1.

Abstract

Introduction: Chagas disease is a chronic infection associated with long-term morbidity. Increased funding and advocacy for drug discovery for neglected diseases have prompted the introduction of several important technological advances, and Chagas disease is among the neglected conditions that has mostly benefited from technological developments. A number of screening campaigns, and the development of new and improved in vitro and in vivo assays, has led to advances in the field of drug discovery.

Areas covered: This review highlights the major advances in Chagas disease drug screening, and how these are being used not only to discover novel chemical entities and drug candidates, but also increase our knowledge about the disease and the parasite. Different methodologies used for compound screening and prioritization are discussed, as well as novel techniques for the investigation of these targets. The molecular mechanism of action is also discussed.

Expert opinion: Technological advances have been executed with scientific rigour for the development of new in vitro cell-based assays and in vivo animal models, to bring about novel and better drugs for Chagas disease, as well as to increase our understanding of what are the necessary properties for a compound to be successful in the clinic. The gained knowledge, combined with new exciting approaches toward target deconvolution, will help identifying new targets for Chagas disease chemotherapy in the future.

Keywords: Chagas disease drug discovery; Trypanosoma cruzi; high content screening; target deconvolution.

Publication types

  • Review

MeSH terms

  • Animals
  • Chagas Disease / drug therapy*
  • Drug Discovery
  • Drug Evaluation, Preclinical
  • Humans
  • Trypanocidal Agents / pharmacology
  • Trypanocidal Agents / therapeutic use
  • Trypanosoma cruzi / drug effects

Substances

  • Trypanocidal Agents