Liliana V Muschietti
University of Buenos Aires, Argentina
Title: Natural sesquiterpene lactones as potential Trypanocidal and Leishmanicidal agents
Biography
Biography: Liliana V Muschietti
Abstract
Chagas disease and Leishmaniasis are life-threatening illnesses that affect mainly the poorest and the most marginalized communities. The scarcity of effective chemotherapy, due to the low investment in the Research and development (R&D) of new drugs, together with a high incidence of side effects, and the emergence of drug resistance phenomena emphasizes the urgent need for new therapeutic agents. Sesquiterpene lactones (STLs) are a large group of naturally occurring terpenoids derived from plants which display a broad spectrum of biological activities including antiprotozoal activity. In this context, this work focuses on the potential of the STLs uvedalin, enhydrin and polymatin B, isolated from Smallanthus sonchifolius, as potential Trypanocidal and Leishmanicidal agents. The three STLs were isolated from S. sonchifolius by bioassay guidedfractionation and their inhibitory effect on the growth of the infective and non-infective forms of Leishmania mexicana and Trypanosoma cruzi was evaluated in vitro. The changes produced by the compounds on the ultrastructure of parasites were examined by Transmission electron microscopy (TEM). Enhydrin and uvedalin were also studied in a murine model of acute
T. cruzi infection. The cytotoxicity of the compounds was evaluated in Vero cells and the selectivity index was calculated. Serum activities of the hepatic enzymes were used as biochemical markers of hepatotoxicity. The three compounds exhibited significant in vitro Leishmanicidal and Trypanocidal activity. The TEM evaluation showed marked ultrastructural alterations, such as an intense vacuolization and mitochondrial swelling in both L. mexicana promastigotes and T. cruzi epimastigotes exposed to the STLs. In the in vivo study, enhydrin and uvedalin displayed a significant decrease in circulating parasites and no signs of hepatotoxicity were detected. Uvedalin, enhydrin and polymatin B may provide valuable leads for the development of new drugs against Chagas disease and Leishmaniasis.