Cysteine proteases as potential targets for anti-trypanosomatid drug discovery

Bioorg Med Chem. 2021 Sep 15:46:116365. doi: 10.1016/j.bmc.2021.116365. Epub 2021 Aug 13.

Abstract

Leishmaniasis and trypanosomiasis are endemic neglected disease in South America and Africa and considered a significant public health problem, mainly in poor communities. The limitations of the current available therapeutic options, including the lack of specificity, relatively high toxicity, and the drug resistance acquiring, drive the constant search for new targets and therapeutic options. Advances in knowledge of parasite biology have revealed essential enzymes involved in the replication, survival, and pathogenicity of Leishmania and Trypanosoma species. In this scenario, cysteine proteases have drawn the attention of researchers and they are being proposed as promising targets for drug discovery of antiprotozoal drugs. In this systematic review, we will provide an update on drug discovery strategies targeting the cysteine proteases as potential targets for chemotherapy against protozoal neglected diseases.

Keywords: Chagas disease; Chemotherapy; Cysteine proteases; Leishmaniasis; Neglected diseases.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Cysteine Proteases / metabolism*
  • Cysteine Proteinase Inhibitors / chemical synthesis
  • Cysteine Proteinase Inhibitors / chemistry
  • Cysteine Proteinase Inhibitors / pharmacology*
  • Drug Discovery*
  • Humans
  • Leishmania / drug effects*
  • Leishmania / enzymology
  • Leishmaniasis / drug therapy
  • Molecular Structure
  • Parasitic Sensitivity Tests
  • Trypanocidal Agents / chemical synthesis
  • Trypanocidal Agents / chemistry
  • Trypanocidal Agents / pharmacology*
  • Trypanosoma / drug effects*
  • Trypanosoma / enzymology
  • Trypanosomiasis / drug therapy

Substances

  • Cysteine Proteinase Inhibitors
  • Trypanocidal Agents
  • Cysteine Proteases