Targeting Trypanothione Reductase, a Key Enzyme in the Redox Trypanosomatid Metabolism, to Develop New Drugs against Leishmaniasis and Trypanosomiases

Molecules. 2020 Apr 21;25(8):1924. doi: 10.3390/molecules25081924.

Abstract

The protozoans Leishmania and Trypanosoma, belonging to the same Trypanosomatidae family, are the causative agents of Leishmaniasis, Chagas disease, and human African trypanosomiasis. Overall, these infections affect millions of people worldwide, posing a serious health issue as well as socio-economical concern. Current treatments are inadequate, mainly due to poor efficacy, toxicity, and emerging resistance; therefore, there is an urgent need for new drugs.

Keywords: protein crystallography; rational drug discovery; structure-based drug design; trypanosomatid infection; trypanothione reductase.

Publication types

  • Review

MeSH terms

  • Antiprotozoal Agents / chemistry*
  • Antiprotozoal Agents / pharmacology*
  • Binding Sites
  • Drug Design
  • Drug Development* / methods
  • Leishmania / drug effects
  • Leishmania / metabolism
  • Models, Molecular
  • Molecular Conformation
  • NADH, NADPH Oxidoreductases / antagonists & inhibitors*
  • NADH, NADPH Oxidoreductases / chemistry*
  • Oxidation-Reduction / drug effects*
  • Protein Binding
  • Protein Multimerization
  • Structure-Activity Relationship
  • Substrate Specificity
  • Trypanosoma / drug effects*
  • Trypanosoma / metabolism*

Substances

  • Antiprotozoal Agents
  • NADH, NADPH Oxidoreductases
  • trypanothione reductase