title: Antimalarial β-carbolines from the New Zealand ascidian Pseudodistoma opacum.
abstract: One tetrahydro-β-carboline, (-)-7-bromohomotrypargine (1), and three alkylguanidine-substituted β-carbolines, opacalines A, B, and C (2-4), have been isolated from the New Zealand ascidian Pseudodistoma opacum. The structures of the metabolites were determined by analysis of mass spectrometric and 2D NMR spectroscopic data. Natural products 2 and 3, synthetic debromo analogues 8 and 9, and intermediate 16 exhibited moderate antimalarial activity toward a chloroquine-resistant strain of Plasmodium falciparum, with an IC50 range of 2.5-14 μM. The biosynthesis of 1-4 is proposed to proceed via a Pictet-Spengler condensation of 6-bromotryptamine and the α-keto acid transamination product of either arginine or homoarginine. Cell separation and 1H NMR analysis of P. opacum identified tetrahydro-β-carboline 1 to be principally located in the zooids, while fully aromatized analogues 2-4 were localized to the test.
authors.affiliation: School of Chemical Sciences, University of Auckland, Private Bag 92019, Auckland, New Zealand.
authors.forename: Susanna T S
authors.initials: ST
authors.lastname: Chan
authors.forename: A Norrie
authors.initials: AN
authors.lastname: Pearce
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Page
authors.forename: Marcel
authors.initials: M
authors.lastname: Kaiser
authors.forename: Brent R
authors.initials: BR
authors.lastname: Copp
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D002243:Carbolines / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D002738:Chloroquine / Q000494:pharmacology; D004351:Drug Resistance / Q000187:drug effects; D015394:Molecular Structure; D009520:New Zealand; D019906:Nuclear Magnetic Resonance, Biomolecular; D010963:Plasmodium falciparum / Q000187:drug effects*; D013237:Stereoisomerism; D014561:Urochordata / Q000737:chemistry*
chemical_list: D000962:Antimalarials; D002243:Carbolines; D002738:Chloroquine