Copper (II) complexes of [1,2,4]triazolo [1,5-a]pyrimidine derivatives as potential anti-parasitic agents.
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.
Department of Parasitology, University of Granada, Severo Ochoa s/n, E-18071 Granada, Spain.
Samira
S
Boutaleb-Charki
Clotilde
C
Marín
Carmen R
CR
Maldonado
María J
MJ
Rosales
Jesus
J
Urbano
Ramon
R
Guitierrez-Sánchez
Miguel
M
Quirós
Juan M
JM
Salas
Manuel
M
Sánchez-Moreno
D000818:Animals; D000977:Antiparasitic Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D002522:Chlorocebus aethiops; D003300:Copper / Q000737:chemistry*; D018360:Crystallography, X-Ray; D015195:Drug Design; D004734:Energy Metabolism / Q000187:drug effects; D007202:Indicators and Reagents; D007891:Leishmania / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D008264:Macrophages / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008958:Models, Molecular; D009243:NAD / Q000378:metabolism; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D011743:Pyrimidines / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology; D014230:Triazoles / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology; D014349:Trypanosoma cruzi / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D014709:Vero Cells
D000977:Antiparasitic Agents; D007202:Indicators and Reagents; D009942:Organometallic Compounds; D011743:Pyrimidines; D014230:Triazoles; D009243:NAD; D003300:Copper