title: Trypanocidal and leishmanicidal activities of sesquiterpene lactones from Ambrosia tenuifolia Sprengel (Asteraceae).
abstract: Bioassay-guided fractionation of the organic extract of Ambrosia tenuifolia Sprengel (Asteraceae) led to the isolation of two bioactive sesquiterpene lactones with significant trypanocidal and leishmanicidal activities. By spectroscopic methods ((1)H- and (13)C-nuclear magnetic resonance, distortionless enhancement by polarization transfer, correlated spectroscopy, heteronuclear multiple-quantum coherence, electron impact-mass spectrometry, and infrared spectroscopy), these compounds were identified as psilostachyin and peruvin. Both compounds showed a marked in vitro trypanocidal activity against Trypanosoma cruzi epimastigotes with 50% inhibitory concentration (IC(50)) values of less than 2 microg/ml. Psilostachyin exerted a significant in vitro activity against the trypomastigote forms of T. cruzi (IC(50), 0.76 microg/ml) and was selected for in vivo testing. Psilostachyin-treated mice had a survival of 100% and lower parasitemia values than control mice. Both compounds were also tested on Leishmania sp. promastigotes: psilostachyin (IC(50), 0.12 microg/ml) and peruvin (IC(50), 0.39 microg/ml) exerted significant leishmanicidal activities. This is the first time that the trypanocidal and leishmanicidal activities of these compounds have been reported. The selectivity index (SI) was employed to evaluate the cytotoxic effect of lactones on T lymphocytes. Although the SIs of both compounds were high for T. cruzi epimastigotes, psilostachyin was more selective against trypomastigotes (SI, 33.8) while peruvin showed no specificity for this parasite. Both compounds presented high selectivity for Leishmania spp. The results shown herein suggest that psilostachyin and peruvin could be considered potential candidates for the development of new antiprotozoal agents against Chagas' disease and leishmaniasis.
authors.affiliation: Cátedra de Farmacognosia, IQUIMEFA (UBA-CONICET), 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: Claudia A
authors.initials: CA
authors.lastname: Anesini
authors.forename: Emilio L
authors.initials: EL
authors.lastname: Malchiodi
authors.forename: Blanca
authors.initials: B
authors.lastname: Freixa
authors.forename: Roser
authors.initials: R
authors.lastname: Vila
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; D014355:Chagas Disease / Q000188:drug therapy; D005260:Female; D006801:Humans; D007783:Lactones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D007894:Leishmania mexicana / Q000187:drug effects; D016773:Leishmaniasis, Cutaneous / Q000188:drug therapy; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008815:Mice, Inbred Strains; D015394:Molecular Structure; D021261:Parasitic Sensitivity Tests; D008517:Phytotherapy; D010946:Plants, Medicinal / Q000737:chemistry*; D012717:Sesquiterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D014344:Trypanocidal Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D014349:Trypanosoma cruzi / Q000187:drug effects
chemical_list: D007783:Lactones; D012717:Sesquiterpenes; D014344:Trypanocidal Agents