Organometallic compounds in the discovery of new agents against kinetoplastid-caused diseases

Eur J Med Chem. 2018 Jul 15:155:459-482. doi: 10.1016/j.ejmech.2018.05.044. Epub 2018 Jun 1.

Abstract

The development of safe and affordable antiparasitic agents effective against neglected tropical diseases is a big challenge of the drug discovery. The drugs currently employed have limitations such as poor efficacy, drug resistance or side effects. Thus, the search for new promising drugs is more and more crucial. Metal complexes and, in particular, organometallic compounds may expand the list of the drug candidates due to the peculiar attributes that the presence of the metal core add to the organic fragment (e.g., redox and structural features, ability to interact with DNA or protein targets, etc.). To date, most organometallic compounds tested as anti-neglected tropical diseases are based on similarities or activity of the organic ligands against other diseases or parasites and/or consist in modification of existing drugs combining the features of the metal moiety and the organic ligands. This review focuses on recent studies (2012-2017) on organometallic compounds in treating kinetoplastid-caused diseases such as Human African trypanosomiasis, Chagas disease and leishmaniasis. This field of research, however, still lacks exhaustive studies to identify of parasitic targets and quantitative structure-activity relationships for a rational drug design.

Keywords: Chagas disease; Leishmania; Metal-based drugs; Organometallic compounds; Trypanosoma.

Publication types

  • Review

MeSH terms

  • Animals
  • Antiparasitic Agents / chemistry
  • Antiparasitic Agents / therapeutic use*
  • Chagas Disease / drug therapy*
  • Dose-Response Relationship, Drug
  • Drug Discovery*
  • Humans
  • Leishmaniasis / drug therapy*
  • Molecular Structure
  • Organometallic Compounds / chemistry
  • Organometallic Compounds / therapeutic use*
  • Structure-Activity Relationship
  • Trypanosomiasis, African / drug therapy*

Substances

  • Antiparasitic Agents
  • Organometallic Compounds