Identification of Active Sesquiterpene Lactones by Bioassay-Guided Fractionation

FRANK FM, ULLOA J, CAZORLA SI, MARAVILLA G, MALCHIODI EL, GRAU A, MARTINO V, CATALÁN C, AND MUSCHIETTI LV

EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE

OXFORD UNIV PRESS

Lugar: Oxford; Año: 2013

1741-427X

In order to find novel plant-derived biologically active compounds against Trypanosoma cruzi, we performed the isolation of three sesquiterpene lactones from the dichloromethane extract of Smallanthus sonchifolius.The isolation of compounds was carried out by bioassay-guided fractionation. Compounds were identified by means of spectroscopic techniques as enhydrin (1), uvedalin (2), and polymatin B (3). These compounds showed a significant trypanocidal activity against the epimastigote forms of the parasite with IC50 values of 0.84 µM, 1.09 µM, and 4.90 µM, respectively. Moreover, after 24 h of treatment with 10 µg/mL of enhydrin or 10 µg/mL of uvedalin, parasiteswere not able to recover their replication rate.Compounds 1 and 2 showed IC50 values of 33.4 µM and 25.0 µM, against T. cruzi trypomastigotes, respectively, while polymatin B was not active. Interestingly, when the three compounds were tested against the intracellular forms of T. cruzi, they were able to inhibit the amastigote replication with IC50 of 5.17 µM, 3.34 µM, and 9.02 µM for 1, 2, and 3, respectively. The cytotoxicity of the compounds was evaluated in Vero cells obtaining CC50 values of 46.5 µM (1), 46.8 µM (2), and 147.3 µM (3). The latter values were compared with the activity against amastigote forms to calculate the selectivity index. According to the results obtained, enhydrin and uvedalin might have potentials as agents against Chagas disease and could serve as lead molecules to develop new drugs.