Drug Metabolism Letters

Zhiyang Zhao
Amgen
Cambridge, MA
USA

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Copper (II) Complexes of [1,2,4]Triazolo [1,5-a]Pyrimidine Derivatives as Potential Anti-Parasitic Agents

Author(s): Samira Boutaleb-Charki, Clotilde Marin, Carmen R. Maldonado, Maria J. Rosales, Jesus Urbano, Ramon Guitierrez-Sanchez, Miguel Quiros, Juan M. Salas, Manuel Sanchez-Moreno.

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 IC50 within the range of the reference drug benznidazole. These compounds, together with C35 were the most effective against L. (V.) peruviana with an IC50 greater than that presented by reference drugs (Pentostam and Glucantim). These compounds were not toxic to the host cell. IC25 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.

Keywords: Trypanosoma cruzi, Leishmania (Viannia) peruviana, triazolo-pyrimidine derivatives, anti-parasitic agents, action mechanism

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Article Details

VOLUME: 3
ISSUE: 1
Year: 2009
Page: [35 - 44]
Pages: 10
DOI: 10.2174/187231209787176317