Psilostachyin C: a natural compound with trypanocidal activity.

SÜLSEN VP; FRANK FM; CAZORLA S; 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

Abstract 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 identified by spectroscopic techniques. Psilostachyin C exerted in vitro trypanocidal activity against Trypanosoma cruzi epimastigotes, trypomastigotes and amastigotes, with 50% inhibitory concentration (IC(50)) values of 0.6, 3.5 and 0.9μg/mL, respectively, and displayed less cytotoxicity against mammalian cells, with a 50% cytotoxic concentration (CC(50)) of 87.5μg/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 0.2μg/mL. In an 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 compared with untreated mice (7.4±1.2×10(5)parasites/mL vs. 12.8±2.0×10(5)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 (IC(50)=1.2μg/mL and 1.5μg/mL, respectively).