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

ELSO O; CAZORLA SI; BIVONA A; CERNY N; MLACHIODI E; CATALAN C; MARTINO V; SULSEN V

Congreso; ResNet NPND Scientific Meeting; 2016

Chagas´ disease and Leishmaniasis,produced by Trypanosoma cruzi and Leishmania spp., respectively areparasitic diseases that affect millions of people and are considered as neglected tropical diseases, within others. Currentdrugs used for the treatment of these diseases have limited efficacy and present many adverseeffects. In view of thissituation, 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 presentinvestigation was to evaluate the effect of minimolide against the infectiveand intracellular forms of T. cruzi,as well as to extend its study to other trypanosomatid, Leishmania sp. Minimolide was isolated afterfractionation of a dichcloromethane extract of M. minima by column chromatography and was identified byspectroscopic methods as previously described [2]. This sesquiterpene lactone was evaluated against the trypomastigote andamastigote forms of T. cruzi at differentconcentrations (0-100 µg/ml), using bloodstreamtrypomastigotes from RA strain and the recombinant Tulahuen strain expressingβ-galactosidase (Tul-β-Gal), respectively.  Minimolide was alsotested against promastigotes of L.amazonensis by the [3H]-Thymidineuptake technique. The cytotoxicity of this compound on mammalian cells wasdetermined on Vero cells using the MTT assay. Minimolide was active againstboth infective and intracellular forms of T.cruzi with IC50 values of 5.9 and 9.2 µg/ml, respectively. Thissesquiterpene lactone was also active against L. amazonensis. When evaluating the cytotoxicity of minimolide onmammalian cells, this compound presented a CC50 of 47.4 µg/ml.  Mininolide displayssignificant activity against both T.cruzi trypomastigotes and amastigotes and also showed in vitro leishmanicidal activity. This compound presented moderate cytotoxicityto mammalian cells. In conclusion, minimolide could be considered as a potential candidate forfurther studies including in vivo assays.Besides, the evaluation of the effects of this compound on the morphology andultrastructure of the parasites and the study of its mechanism of action couldbe of interest.