Copper (II) complexes of [1,2,4]triazolo [1,5-a]pyrimidine derivatives as potential anti-parasitic agents

Drug Metab Lett. 2009 Jan;3(1):35-44. doi: 10.2174/187231209787176317.

Abstract

Anti-proliferative effects are described for newly synthesised copper (II) complexes of two triazolo-pyrimidine derivatives (1,2,4-triazolo-[1,5-a]pyrimidine, tp, and 5,7-dimethyl 1,2,4-triazolo-[1,5-a]pyrimidine, dmtp) against to Trypanosoma cruzi and Leishmania (Viannia) peruviana. Of the compounds assayed, those that presented the ligand tp and auxiliary ligand 1,10-phenanthroline (C24b, C49) were most highly active against to T. cruzi with IC(50) within the range of the reference drug benznidazole. These compounds, together with C35 were the most effective against L. (V.) peruviana with an IC(50) greater than that presented by reference drugs (Pentostam and Glucantim). These compounds were not toxic to the host cell. IC(25) diminished the infection capacity and severely reduced the multiplication of intracellular forms of T. cruzi, and L. (V.) peruviana. In the case of T. Cruzi, the transformation to trypomastigote was seriously depressed. Copper (II) complexes C24b, C49 and C35, acted on the energy metabolism of the parasites at the level of the NAD(+)/NADH balance and at the level of the organelle membranes, causing degradation and cell death.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiparasitic Agents / chemical synthesis*
  • Antiparasitic Agents / pharmacokinetics
  • Antiparasitic Agents / pharmacology*
  • Chlorocebus aethiops
  • Copper / chemistry*
  • Crystallography, X-Ray
  • Drug Design
  • Energy Metabolism / drug effects
  • Indicators and Reagents
  • Leishmania / drug effects*
  • Leishmania / metabolism
  • Leishmania / ultrastructure
  • Macrophages / metabolism
  • Magnetic Resonance Spectroscopy
  • Mice
  • Models, Molecular
  • NAD / metabolism
  • Organometallic Compounds / chemical synthesis*
  • Organometallic Compounds / pharmacokinetics
  • Organometallic Compounds / pharmacology*
  • Pyrimidines / chemical synthesis
  • Pyrimidines / pharmacokinetics
  • Pyrimidines / pharmacology
  • Triazoles / chemical synthesis
  • Triazoles / pharmacokinetics
  • Triazoles / pharmacology
  • Trypanosoma cruzi / drug effects*
  • Trypanosoma cruzi / metabolism
  • Trypanosoma cruzi / ultrastructure
  • Vero Cells

Substances

  • Antiparasitic Agents
  • Indicators and Reagents
  • Organometallic Compounds
  • Pyrimidines
  • Triazoles
  • NAD
  • Copper