Synthesis and trypanocidal activity of a furofuran lignan against trypomastigote and amastigote forms of Trypanosoma Cruzi

Chagas disease, which affects approximately 8 million people in Latin American and more than 25 million people are at risk of this infection, is a neglected tropical disease caused by the protozoan Trypanosoma cruzi. Drugs currently used to treat it, such as benznidazole, do not completely eliminate the trypomastigote forms (present in the blood), are ineffective against the intracellular stage of the parasite and cause some side effects. In this work, a furofuran lignan was obtained by oxidative coupling of ferulic acid with FeCl₃ in presence of O₂, according to Ahmed, 1973. Then, it was evaluated in vitro against trypomastigote and amastigote forms of T. cruzi. The results showed that this lignan presents potent tripanocidal activity since it induces trypomastigote and amastigote lysis with IC₅₀ values of 9.3 and 7.3µmol/L, respectively. On the other hand, the direct effect of benznidazole, the positive control, was also evaluated and it showed an IC₅₀ value of 1.9µmol/L on trypomastigotes and an IC₅₀ of 69.2µmol/L against the other form tested. These results indicate that this lignan is promising compound that could be used for the development of a new trypanocidal agent, therefore further studies are in progress to elucidate it mechanism of action. The authors thank FAPESP and CNPq for their fellowships. Ahmed, R., Lehner, M., Stevenson, R. Tetrahedron, 29, 3753–3759, 1973.