Boutaleb-Charki Samira, Marín Clotilde, Maldonado Carmen R, Rosales María J, Urbano Jesus, Guitierrez-Sánchez Ramon, Quirós Miguel, Salas Juan M, Sánchez-Moreno Manuel
Department of Parasitology, University of Granada, Severo Ochoa s/n, E-18071 Granada, Spain.
Drug Metab Lett. 2009 Jan;3(1):35-44. doi: 10.2174/187231209787176317.
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.
已报道了两种三唑并嘧啶衍生物（1,2,4-三唑并-[1,5-a]嘧啶，tp，以及5,7-二甲基-1,2,4-三唑并-[1,5-a]嘧啶，dmtp）新合成的铜（II）配合物对克氏锥虫和秘鲁利什曼原虫（维氏利什曼原虫）的抗增殖作用。在所检测的化合物中，那些含有配体tp和辅助配体1,10-菲咯啉的化合物（C24b、C49）对克氏锥虫活性最高，其半数抑制浓度（IC50）在参考药物苯硝唑的范围内。这些化合物与C35一起对秘鲁利什曼原虫（维氏利什曼原虫）最有效，其IC50大于参考药物（喷他脒和葡糖胺锑）的IC50。这些化合物对宿主细胞无毒。IC25降低了感染能力，并严重减少了克氏锥虫和秘鲁利什曼原虫（维氏利什曼原虫）细胞内形式的增殖。就克氏锥虫而言，向 trypomastigote 的转化受到严重抑制。铜（II）配合物C24b、C49和C35在NAD(+)/NADH平衡水平和细胞器膜水平上作用于寄生虫的能量代谢，导致降解和细胞死亡。
