Triazolopyrimidine compounds containing first-row transition metals and their activity against the neglected infectious Chagas disease and leishmaniasis

Eur J Med Chem. 2014 Oct 6:85:526-34. doi: 10.1016/j.ejmech.2014.08.026. Epub 2014 Aug 10.

Abstract

Leishmaniasis and Chagas disease remain a significant global problem. Current treatments have serious disadvantage due to cost, toxicity, long therapy duration and resistance. In the last years increasing interest has arisen in drug development to fight both diseases. Recently, metal-based drugs have revealed as promising drugs in a variety of therapeutic areas. Herein we describe six newly synthesized transition metal complexes with a bioactive molecule 5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidine (dmtp). All of them have been characterized by X-ray, spectroscopic and thermal methods. In vitro and in vivo studies (murine model) on the antiproliferative activity of these complexes against Leishmania spp. (Leishmania infantum, Leishmania braziliensis) and Trypanosoma cruzi have been carried out. Our results reveal a strong potential of three of the assayed compounds as antiparasitic agents against the above-mentioned infectious diseases.

Keywords: Leishmania; Metal; Triazolopyrimidine; Trypanosoma cruzi.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chagas Disease / drug therapy
  • Chagas Disease / parasitology*
  • Chlorocebus aethiops
  • Extracellular Space / drug effects
  • Extracellular Space / parasitology
  • Female
  • Inhibitory Concentration 50
  • Intracellular Space / drug effects
  • Intracellular Space / parasitology
  • Leishmania braziliensis / drug effects
  • Leishmania infantum / drug effects
  • Leishmaniasis / drug therapy
  • Leishmaniasis / parasitology*
  • Mice
  • Models, Molecular
  • Molecular Conformation
  • Organometallic Compounds / chemistry*
  • Organometallic Compounds / pharmacology*
  • Organometallic Compounds / therapeutic use
  • Organometallic Compounds / toxicity
  • Transition Elements / chemistry*
  • Triazoles / chemistry*
  • Trypanocidal Agents / chemistry
  • Trypanocidal Agents / pharmacology
  • Trypanocidal Agents / therapeutic use
  • Trypanocidal Agents / toxicity
  • Trypanosoma cruzi / drug effects
  • Vero Cells

Substances

  • Organometallic Compounds
  • Transition Elements
  • Triazoles
  • Trypanocidal Agents