Activities of Pt(II) and Ru(III) triazole-pyrimidine complexes against Trypanosoma cruzi and T. brucei brucei

Pharmacology. 2004 Feb;70(2):83-90. doi: 10.1159/000074672.

Abstract

We studied the biological activity of three newly synthesized metal complexes of triazole-pyrimidine derivatives that were previously observed to inhibit in vitro growth of epimastigotes of Trypanosoma cruzi and procyclic forms of Trypanosoma brucei brucei. We analyzed the possible inhibitory effect of these compounds on the synthesis of DNA, RNA and protein, ultrastructure and excretion of metabolites by these parasites. RNA synthesis was inhibited by all three complexes assayed. These complexes also led to anomalies of the main organelles (e.g. nucleus, kinetoplast and mitochondria). In addition, these complexes may be capable of altering the excretion of metabolites by the parasites.

MeSH terms

  • Animals
  • Biotransformation
  • DNA, Protozoan / biosynthesis
  • Magnetic Resonance Spectroscopy
  • Organometallic Compounds / metabolism
  • Organometallic Compounds / pharmacology*
  • Organoplatinum Compounds / metabolism
  • Organoplatinum Compounds / pharmacology*
  • Protozoan Proteins / biosynthesis
  • Pyrimidines / metabolism
  • Pyrimidines / pharmacology*
  • RNA, Protozoan / biosynthesis
  • Ruthenium / metabolism
  • Ruthenium / pharmacology*
  • Triazoles / metabolism
  • Triazoles / pharmacology*
  • Trypanosoma brucei brucei / drug effects*
  • Trypanosoma brucei brucei / metabolism
  • Trypanosoma brucei brucei / ultrastructure
  • Trypanosoma cruzi / drug effects*
  • Trypanosoma cruzi / metabolism
  • Trypanosoma cruzi / ultrastructure
  • Uridine / metabolism

Substances

  • DNA, Protozoan
  • Organometallic Compounds
  • Organoplatinum Compounds
  • Protozoan Proteins
  • Pyrimidines
  • RNA, Protozoan
  • Triazoles
  • Ruthenium
  • Uridine