MALCHIODI Emilio Luis
Psilostachyin C: a natural compound with trypanocidal activity
SÜLSEN VP, FRANK FM, CAZORLA SI, BARRERA P, FREIXA B, VILA R, SOSA MA, MALCHIODI EL, MUSCHIETTI LV, MARTINO VS
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
ELSEVIER SCIENCE BV
Año: 2011 vol. 37 p. 536 - 543
The antiprotozoal activity of the sesquiterpene lactone psilostachyin C has been investigated. This natural compound was isolated from the species Ambrosia scabra by bioassay-guided fractionation and identified by spectroscopic techniques. Psilostachyin C exerted in vitro trypanocidal activity against Trypanosoma cruzi epimastigotes, trypomastigotes and amastigotes with 50% inhibitory concentration (IC50) values of 0.6, 3.5 and 0.9 µg/ml respectively, displaying less cytotoxicity on mammalian cells with a 50% cytotoxic concentration (CC50) value of 87.5 µg/ml. Interestingly, this compound induced ultrastructural alterations, as seen by transmission electron microscopy, in which vacuolization and structure appearance resembling multivesicular bodies were observed even at a concentration as low as 0.2 µg/ml. In the in vivo assay, a significant reduction in the number of circulating parasites was found in T. cruzi infected mice treated with psilostachyin C for 5 days when compared to untreated ones ([7.4 ± 1.2] x 105 versus [12.8 ± 2.0] x 105 parasites/ml) at the peak of parasitemia. According to these results, psilostachyin C may be considered a promising template for the design of novel trypanocidal agents. In addition, psilostachyin C inhibited the growth of Leishmania mexicana and L. amazonensis promastigotes (IC50=1.2 and 1.5 µg/ml, respectively).