Polypharmacology in the Treatment of Chagas Disease

Curr Med Chem. 2019;26(23):4476-4489. doi: 10.2174/0929867325666180410101728.

Abstract

The current treatment of Chagas disease is based on monopharmacology where the used drugs have limited efficacy and severe side effects. In order to overcome these limitations, some tools have been described including the development or isolation of new drugs, drug repositioning, and polypharmacology. Here, we review the polypharmacology strategy where compounds belonging to different structural chemotypes were combined in order to affect different biochemical pathways of T. cruzi parasite. Therefore ergosterol biosynthesis inhibitors, anti-inflammatory agents, cardiac dysfunction drugs, trypanothione reductase inhibitors, vitamins, between others, were combined looking for new anti-Chagas treatment. Natural products were also used in the application of this strategy.

Keywords: Chagas disease; antagonism; cardiac dysfunction drugs; isobologram; polypharmacology; synergism..

Publication types

  • Review

MeSH terms

  • Animals
  • Biological Products / chemistry
  • Biological Products / pharmacology*
  • Chagas Disease / drug therapy*
  • Humans
  • Molecular Structure
  • Polypharmacology
  • Trypanocidal Agents / chemistry
  • Trypanocidal Agents / pharmacology*
  • Trypanosoma cruzi / drug effects

Substances

  • Biological Products
  • Trypanocidal Agents