title: Psilostachyin C: a natural compound with trypanocidal activity.
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 0.9 μg/mL, respectively, and displayed less cytotoxicity against mammalian cells, with a 50% cytotoxic concentration (CC(50)) 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 × 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)=1.2 μg/mL and 1.5 μg/mL, respectively).
authors.affiliation: Cátedra de Farmacognosia, IQUIMEFA (UBA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956 (1113), Buenos Aires, Argentina.
authors.forename: Valeria P
authors.initials: VP
authors.lastname: Sülsen
authors.forename: Fernanda M
authors.initials: FM
authors.lastname: Frank
authors.forename: Silvia I
authors.initials: SI
authors.lastname: Cazorla
authors.forename: Patricia
authors.initials: P
authors.lastname: Barrera
authors.forename: Blanca
authors.initials: B
authors.lastname: Freixa
authors.forename: Roser
authors.initials: R
authors.lastname: Vila
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Sosa
authors.forename: Emilio L
authors.initials: EL
authors.lastname: Malchiodi
authors.forename: Liliana V
authors.initials: LV
authors.lastname: Muschietti
authors.forename: Virginia S
authors.initials: VS
authors.lastname: Martino
mesh_terms: D031164:Ambrosia / Q000737:chemistry; D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology* / Q000633:toxicity; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D014355:Chagas Disease / Q000188:drug therapy; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D020128:Inhibitory Concentration 50; D007894:Leishmania mexicana / Q000187:drug effects; D008297:Male; D051379:Mice; D046529:Microscopy, Electron, Transmission; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity; D012376:Rodent Diseases / Q000188:drug therapy; D012717:Sesquiterpenes / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity; D016896:Treatment Outcome; D014349:Trypanosoma cruzi / Q000187:drug effects* / Q000648:ultrastructure
chemical_list: D000981:Antiprotozoal Agents; D010936:Plant Extracts; D012717:Sesquiterpenes