Psilostachyin C: a natural compound with trypanocidal activity

• Published in: International journal of antimicrobial agents 2011-06, Vol.37 (6), p.536-543
• Main Authors: Sülsen, Valeria P, Frank, Fernanda M, Cazorla, Silvia I, Barrera, Patricia, Freixa, Blanca, Vila, Roser, Sosa, Miguel A, Malchiodi, Emilio L, Muschietti, Liliana V, Martino, Virginia S
• Format: Article
• Language: English
• Subjects: amastigotes; Ambrosia; Ambrosia - chemistry; Ambrosia scabra; Animals; anti-infective agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiprotozoal Agents - pharmacology; Antiprotozoal Agents - toxicity; Biological and medical sciences; Cell Line; Cell Survival - drug effects; Chagas Disease - drug therapy; cytotoxicity; Disease Models, Animal; epimastigotes; Female; fractionation; growth retardation; Humans; Infectious Disease; Inhibitory Concentration 50; Leishmania amazonensis; Leishmania mexicana; Leishmania mexicana - drug effects; Leishmanicidal activity; Male; Medical sciences; Mice; Microscopy, Electron, Transmission; parasitemia; parasites; Pharmacology. Drug treatments; Plant Extracts - isolation & purification; Plant Extracts - pharmacology; Plant Extracts - toxicity; promastigotes; Psilostachyin C; Rodent Diseases - drug therapy; Sesquiterpene lactones; Sesquiterpenes - isolation & purification; Sesquiterpenes - pharmacology; Sesquiterpenes - toxicity; spectroscopy; transmission electron microscopy; Treatment Outcome; Trypanocidal activity; Trypanosoma cruzi; Trypanosoma cruzi - drug effects; Trypanosoma cruzi - ultrastructure; trypomastigotes
• ISSN: 0924-8579; 1872-7913
• DOI: 10.1016/j.ijantimicag.2011.02.003

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 μg/mL, respectively, and displayed less cytotoxicity against mammalian cells, with a 50% cytotoxic concentration (CC50 ) of 87.5 μg/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 μg/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 μg/mL and 1.5 μg/mL, respectively).