Current advances in drug discovery for Chagas disease

Eur J Med Chem. 2018 Jul 15:155:824-838. doi: 10.1016/j.ejmech.2018.06.040. Epub 2018 Jun 20.

Abstract

Chagas disease, also known as American trypanosomiasis, is one of the 17 neglected tropical diseases (NTDs) according to World Health Organization. It is estimated that 8-10 million people are infected worldwide, mainly in Latin America. Chagas disease is caused by the parasite Trypanosoma cruzi and is characterized by two phases: acute and chronic. The current therapy for Chagas disease is limited to drugs such as nifurtimox and benznidazole, which are effective in treating only the acute phase of the disease. In addition, several side effects ranging from hypersensitivity to bone marrow depression and peripheral polyneuropathy have been associated with these drugs. Therefore, the current challenge is to find new effective and safe drugs against this NTD. The aim of this review is to describe the advances in the medicinal chemistry of new anti-chagasic compounds reported in the literature in the last five years. We report promising prototypes for drug discovery identified through target-based and phenotype-based strategies and present some important targets for the development of new synthetic compounds.

Keywords: Chagas disease; New compounds; New drugs; T. cruzi.

Publication types

  • Review

MeSH terms

  • Animals
  • Chagas Disease / drug therapy*
  • Chemistry, Pharmaceutical
  • Dose-Response Relationship, Drug
  • Drug Discovery*
  • Humans
  • Molecular Structure
  • Parasitic Sensitivity Tests
  • Structure-Activity Relationship
  • Trypanocidal Agents / chemistry
  • Trypanocidal Agents / pharmacology*
  • Trypanosoma cruzi / drug effects*

Substances

  • Trypanocidal Agents