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

0924-8579

In this study, the antiprotozoal activity of the sesquiterpene lactone psilostachyin C was investigated. This natural compound was isolated from Ambrosia scabra by bioassay-guided fractionation and was identifiedby spectroscopic techniques. Psilostachyin C exerted in vitro trypanocidal activity against Trypanosoma cruzi epimastigotes, trypomastigotes and amastigotes, with 50% inhibitory concentration (IC50) valuesof 0.6, 3.5 and 0.9g/mL, respectively, and displayed less cytotoxicity against mammalian cells, with a 50% cytotoxic concentration (CC50) of 87.5g/mL. Interestingly, this compound induced ultrastructural alterations, as seen by transmission electron microscopy, in which vacuolisation and a structural appearance resembling multivesicular bodies were observed even at a concentration as low as 0.2g/mL. In an in vivo assay, a significant reduction in the number of circulating parasites was found in T. cruzi-infectedmice treated with psilostachyin C for 5 days compared with untreated mice (7.4±1.2×105 parasites/mL vs. 12.8±2.0×105 parasites/mL) at the peak of parasitaemia. 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 Leishmania amazonensis promastigotes (IC50 = 1.2g/mL and 1.5g/mL, respectively).