Effect of the sesquiterpene lactone minimolide on Trypanosoma cruzi and Leishmania amazonensis

ORLANDO GERMAN ELSO; NATACHA CERNY; VIRGINIA SUSANA MARTINO; AUGUSTO ERNESTO BIVONA; CESAR CATALAN; SILVIA I CAZORLA; EMILIO L MALCHIODI; VALERIA PATRICIA SULSEN

Bogotá

Congreso; 3rd Research Network Natural Products against Neglected Diseases ? ResNet NPND Scientific Meeting; 2016

Chagas´ disease and Leishmaniasis, produced by Trypanosoma cruzi and Leishmania spp., respectively are parasitic diseases that affect millions of people and are considered as neglected tropical diseases, within others. Current drugs used for the treatment of these diseases have limited efficacy and present many adverse effects. In view of this situation, new drugs to treat these parasitoses are needed. We have reported the in vitro trypanocidal activity of minimolide, a sesquiterpene lactone isolated from Mikania minima (Asteraceae), against Trypanosoma cruzi epimastigotes [1]. The aim of the present investigation was to evaluate the effect of minimolide against the infective and intracellular forms of T. cruzi, as well as to extend its study to other trypanosomatid, Leishmania sp. Minimolide was isolated after fractionation of a dichcloromethane extract of M. minima by column chromatography and was identified by spectroscopic methods as previously described [2]. This sesquiterpene lactone was evaluated against the trypomastigote and amastigote forms of T. cruzi at different concentrations (0-100 µg/ml), using bloodstream trypomastigotes from RA strain and the recombinant Tulahuen strain expressing β-galactosidase (Tul-β-Gal), respectively. Minimolide was also tested against promastigotes of L. amazonensis by the [3H]-Thymidine uptake technique. The cytotoxicity of this compound on mammalian cells was determined on Vero cells using the MTT assay. Minimolide was active against both infective and intracellular forms of T. cruzi with IC50 values of 5.9 and 9.2 µg/ml, respectively. This sesquiterpene lactone was also active against L. amazonensis. When evaluating the cytotoxicity of minimolide on mammalian cells, this compound presented a CC50 of 47.4 µg/ml. Mininolide displays significant activity against both T. cruzi trypomastigotes and amastigotes and also showed in vitro leishmanicidal activity. This compound presented moderate cytotoxicity to mammalian cells. In conclusion, minimolide could be considered as a potential candidate for further studies including in vivo assays. Besides, the evaluation of the effects of this compound on the morphology and ultrastructure of the parasites and the study of its mechanism of action could be of interest. Keywords: sesquiterpene lactone, Trypanosoma cruzi, Leishmania sp., Mikania minimaAcknowledgements: This work was supported by grants from PICT 1753 (2012-2015) (The National Agency for Science and Technology Promotion), PIP 0324 (National Scientific and Technical Research Council), and UBACYT 20020130200270 (University of Buenos Aires).References[1] Fabian L, et al., 2013. Mini Reviews in Medicinal Chemistry, 13, 1407-1414.[2] Cuenca MR, et al., 1993. Phytochemistry, 32, 1509-1513.