Psilostachyn C: a natural compound with trypanocidal activity

SULSEN V; FRANK F; CAZORLA S; BARRERA P; FREIXA B; VILA R; SOSA M; MALCHIODI E; MUSCHIETTI L; MARTINO V

INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS

ELSEVIER SCIENCE BV

Lugar: Birmingham; Año: 2010 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 (IC50) values of 0.6, 3.5 and 0.9 mg/mL, respectively, and displayed less cytotoxicity against mammalian cells, with a 50% cytotoxic concentration (CC50) of 87.5 mg/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 0.2 mg/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 ´ 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 = 1.2 mg/mL and 1.5 mg/mL, respectively).