Activities of Pt(II) and Ru(III) Triazole-Pyrimidine Complexes against <i>Trypanosoma cruzi</i> and <i>T. brucei brucei</i>

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 bruceibrucei. 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.

Therapeutic Potential of New Pt(II) and Ru(III) Triazole-Pyrimidine Complexes against <i>Leishmania donovani</i>

“…The data of the present study, together with those of previous works [8][9][10] concerning the effect of these triazole-pyrimidine derivatives against Trypanosoma cruzi and Trypanosoma brucei brucei, indicates that we are now in a position to affirm that these compounds represent a promising option in the fight against such major parasites as those that cause Chagas' disease, African trypanosomiasis and different manifestations of leishmaniasis. Future research is needed to study the in vivo effects of these compounds and to gain a fuller understanding of their biological action.…”

“…Regarding molecular structure, these in vitro studies show that the anti-leishmanial activity of the triazolepyrimidine derivatives tested may be due to the nature of the ligand carried in their structure [10]. The compounds SPIV and SPVI have 7HtpO as the ligand, whereas SPV has 5HtpO, and the ability of these derivatives to inhibit parasite growth apparently depended on the ligand.…”

“…All these data reflect the need to continue the search for effective chemotherapy against this group of parasitic protozoa, since in addition to the problems posed by the drugs currently being used (high cost, prolonged treatment, toxicity, resistance), leishmaniasis affects areas of the world which cannot afford the necessary controls even when these are available [7]. Previous studies in our laboratory have revealed that triazole-pyrimidine derivatives may hold the solution to these problems [8][9][10]. That is, the in vitro biological activity of these compounds is promising, since some can be considered mimetic of purine bases and, due to the similarity, several researchers have studied these compounds as chemotherapeutic agents, vasodilators and inhibitors of microorganism growth [11].…”

Cytotoxicity of three new triazolo-pyrimidine derivatives against the plant trypanosomatid: Phytomonas sp. isolated from Euphorbia characias

“…A decrease in the incorporation of 5-[ 3 H]-uridine, indicates a disturbance of RNA synthesis induced by SPVI. These data, together with those previously gathered by our group (Luque et al 2000b, Magán et al 2004), point to the possibility that one of the possible targets of the triazolo-pyrimidine derivatives is nucleic acid synthesis. Leucine incorporation was also visibly diminished by treatment with SPVI, suggesting that this compound can act directly on protein synthesis (Zollner 1993), or can indirectly affect ribosomal factors.…”

“…To finding of an effective chemotherapy against Phytomonas spp. has not only a direct economic interest, but since these parasites present metabolic routes similar to those of other Trypanosomatidae pathogenic to humans and animals, they represent also a potential biological model (Uttaro et al 1999, Magán et al 2004.…”