title: ent-Pimarane and ent-Kaurane Diterpenes from Aldama discolor (Asteraceae) and Their Antiprotozoal Activity.
abstract: Aldama discolor (syn.Viguiera discolor) is an endemic Asteraceae from the Brazilian "Cerrado", which has not previously been investigated for its chemical constituents and biological activity. Diterpenes are common secondary metabolites found in Aldama species, some of which have been reported to present potential antiprotozoal and antimicrobial activities. In this study, the known ent-3-α-hydroxy-kaur-16-en-18-ol (1), as well as three new diterpenes, namely, ent-7-oxo-pimara-8,15-diene-18-ol (2), ent-2S,4S-2-19-epoxy-pimara-8(3),15-diene-7β-ol (3) and ent-7-oxo-pimara-8,15-diene-3β-ol (4), were isolated from the dichloromethane extract of A. discolor leaves and identified by means of MS and NMR. The compounds were assayed in vitro against Trypanosoma brucei rhodesiense, T. cruzi and Leishmania donovani, Plasmodium falciparum and also tested for cytotoxicity against mammalian cells (L6 cell line). The ent-kaurane 1 showed significant in vitro activity against both P. falciparum (IC 50 = 3.5 μ M) and L. donovani (IC 50 = 2.5 μ M) and ent-pimarane 2 against P. falciparum (IC 50 = 3.8 μ M). Both compounds returned high selectivity indices (SI >10) in comparison with L6 cells, which makes them interesting candidates for in vivo tests. In addition to the diterpenes, the sesquiterpene lactone budlein A (5), which has been reported to possess a strong anti-T. b. rhodesiense activity, was identified as major compound in the A. discolor extract and explains its high activity against this parasite (100% growth inhibition at 2 μ g/mL).
authors.affiliation: Institute of Pharmaceutical Biology and Phytochemistry (IPBP), University of Münster, PharmaCampus Corrensstraße 48, Münster D-48149, Germany. nogueira@uni-muenster.de.
authors.forename: Mauro S
authors.initials: MS
authors.lastname: Nogueira
authors.affiliation: AsterBioChem Research Team, Laboratory of Pharmacognosy, School of Pharmaceutical Sciences of Ribeirão Preto, USP, Av. do Café s/n, Ribeirão Preto-SP 14040-903, Brazil. febcosta@fcfrp.usp.br.
authors.forename: Fernando B
authors.initials: FB
authors.lastname: Da Costa
authors.affiliation: Swiss Tropical and Public Health Institute (Swiss TPH), Socinstr. 57, Basel CH-4051, Switzerland. reto.brun@unibas.ch.|University of Basel, Petersplatz 1, Basel CH-4003, Switzerland. reto.brun@unibas.ch.
authors.forename: Reto
authors.initials: R
authors.lastname: Brun
authors.affiliation: Swiss Tropical and Public Health Institute (Swiss TPH), Socinstr. 57, Basel CH-4051, Switzerland. marcel.kaiser@unibas.ch.|University of Basel, Petersplatz 1, Basel CH-4003, Switzerland. marcel.kaiser@unibas.ch.
authors.forename: Marcel
authors.initials: M
authors.lastname: Kaiser
authors.affiliation: Institute of Pharmaceutical Biology and Phytochemistry (IPBP), University of Münster, PharmaCampus Corrensstraße 48, Münster D-48149, Germany. thomschm@uni-muenster.de.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Schmidt
mesh_terms: D045784:Abietanes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D000981:Antiprotozoal Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D019659:Asteraceae / Q000737:chemistry*; D002460:Cell Line; D045786:Diterpenes, Kaurane / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D006801:Humans; D007893:Leishmania donovani / Q000254:growth & development*; D010963:Plasmodium falciparum / Q000254:growth & development*; D016833:Trypanosoma brucei rhodesiense / Q000254:growth & development*; D014349:Trypanosoma cruzi / Q000254:growth & development*
chemical_list: D045784:Abietanes; D000981:Antiprotozoal Agents; D045786:Diterpenes, Kaurane
keywords: Aldama discolor; Asteraceae; Leishmania donovani; Plasmodium falciparum; Trypanosoma brucei rhodesiense; Trypanosoma cruzi; Viguiera discolor; antiprotozoal activity; ent-kaurane; ent-pimarane