Activity of Pt(II) and Ru(III) Triazolopyrimidine Complexes Against Parasites of the Genus Leishmania, Trypanosomas and Phytomonas

Abstract

The synthesis and characterization of two Pt(II) Complexes with the isomeric ligands 4,5-dihydro-5-oxo- [1,2,4]triazolo-[ 1,5-a]pyrimidine (5HtpO) and 4,7-dihydro-7-oxo-[ 1,2,4]-triazolo-[ 1,5-a]pyrimidine (7HtpO) are described, as well as a Ru(III) complex with 7HtpO. The crystal structure of cis-[PtCl2(7HtpO)2].2H2O has been solved by X-ray diffraction analysis. In vitro activity of the new isolated complexes against the epimastigote form of T. cruzi, procyclic form of T. b. brucei and promastigote form of L. donnovani and P. characias has also been studied. The three complexes markedly affect the growth of the parasites and none of them shows cytotoxicity against macrophage of the J774.2 line at the heaviest dosages used.

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

“…The fact that SPIV was the most effective complex inhibiting RNA synthesis would explain the strong in vitro growth inhibition of T. cruzi and T. b. brucei observed in our previous studies [10]. However, the three complexes do not appear to inhibit DNA or protein synthesis.…”

“…However, the three complexes do not appear to inhibit DNA or protein synthesis. Also, we broadened this study, testing the effects of the three triazole-pyrimidine derivatives on the in vitro growth of promastigote forms of L. donovani and P. characias, finding a highly significant inhibition [10], as well as very encouraging results based on the incorporation of radioactive isotopes, ultrastructural studies and the excretion of end metabolites [unpubl. data].…”

“…The compounds assayed had been synthesized by the Department of Inorganic Chemistry of the Faculty of Science of the University of Granada (Spain) [10]. All the complexes presented ligands 7HtpO: 4,7 dihydro-7-oxo- [1,2,4] [4, H]leucine (specific activity 35-70 Ci/mmol), obtained from the Radiochemical Center (UK).…”

“…Two of these carry the metal ion Pt(II) and one Ru(III). All triazole-pyrimidine compounds elicit a marked in vitro growth inhibition of epimastigotes of T. cruzi and procyclic forms of T. b. brucei [10].…”

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

“…In a same field (data not shown), parasites showed very different degrees of alteration. In this experiment, we use a concentration of 5 µM, because this value is roughly 10-fold lower than that of IC 50 found in prior studies (Salas et al 2001). …”