Trypanocidal action of 2,4-dichloro-6-phenylphenoxyethyl diethylamine hydrobromide (Lilly 18947) on Trypanosoma cruzi

To study the effect of the inhibitor of cytochrome P450 known as Lilly 18947 (2,4 dichloro-6 phenylphenoxy ethyl diethylamine) on Trypanosoma cruzi.

Trypanosoma cruzi epimastigotes were grown in culture, in absence or in presence of drug. The inhibition of its growth was followed by daily counting using a Neubauer chamber. The effect of Lilly 18947 on the parasite ultrastructure was examined by electron microscopy. To test the effect of different concentrations of drug on the parasite cycle, Vero cells were inoculated with trypomastigotes (RA strain) and after 72 h the percentage of infected cells and the number of intracellular parasites were estimated and expressed as the endocytic index.

Growth of epimastigotes was inhibited by Lilly 18947. Concentrations as low a s 50 micromol/L resulted in a complete disappearance of the parasites in culture by the fourth day. With lower concentrations, little growth was observed and total (25 micro mol/L) or partial lysis (10 micromol/L) were registered by the eighth day of culture. Incubation of epimastigotes with 50 micromol/L of Lilly 18947 resulted in an early damage to cellular structures. Initial signs were dilatation of perinuclear membranes and mitochondria swelling. The infectivity of trypomastigotes to Vero cells in culture was nearly abolished at 15 and 30 micromol/L concentrations of the drug.

Lilly 18947 was able to harm Trypanosoma cruzi membrane functions leading to t he loss of its infective properties and its death.