title: Toxic aromatic compounds from fruits of Narthecium ossifragum L.
abstract: The intake of Narthecium ossifragum, commonly known as bog asphodel, has been associated with toxic effects observed in sheep for centuries. Although the plant has been studied for five centuries little is known about its chemical constituents. Six previously undescribed natural products, naringenin(3 → 6″)luteolin, naringenin(3 → 6″)chrysoeriol, liovil 4-O-β-glucopyranoside, 2,6-dimethoxy cinnamic acid, (E)-4-(3-hydroxy-2,2-dimethylchroman-6-yl)but-3-en-2-one and (E)-4-(4-(((E)-4-hydroxy-3-methylbut-2-en-1-yl)oxy)phenyl)but-3-en-2-one, have been identified from fruits of N. ossifragum for the first time. In addition, the rare natural product 4-hydroxy-3-(3-methylbut-2-enyl)benzaldehyde and the five known compounds 4-hydroxycinnamic acid, quercetin 3,3'-dimethyl ether, quercetin 3,7-dimethyl ether, chrysoeriol 7-O-β-glucopyranoside and the di-C-glycosylflavone isoschaftoside were all characterized for the first time from the fruits of N. ossifragum. The discovery of sufficient amounts of 4-hydroxy-3-(3-methylbut-2-enyl)benzaldehyde in fresh plant material of N. ossifragum to allow complete structure elucidation by NMR and HRMS supports the possibility that fungi associated with N. ossifragum may be able to produce enough toxins to play a significant role in the pathogenicity of N. ossifragum. 4-Hydroxy-3-(3-methylbut-2-enyl)benzaldehyde showed mild toxicity towards normal rat kidney (NRK) and more profound activity towards MOLM13 acute myeloid leukemia cells (IC50= 430 μM and 68 μM, respectively). Naringenin(3 → 6″)luteolin had IC50of 230 μM towards NRK cells, and 115 μM towards MOLM13 cells. Microscopic evaluation suggests that these two compounds induce cell death by different mechanisms.
authors.affiliation: Department of Chemistry and Centre for Pharmacy, University of Bergen, Allégt. 41, N-5007 Bergen, Norway.
authors.forename: Marita
authors.initials: M
authors.lastname: Vu
authors.affiliation: Department of Clinical Science and Centre for Pharmacy, University of Bergen, Norway; Hospital Pharmacies Enterprise, Western Norway, Bergen, Norway.
authors.forename: Lars
authors.initials: L
authors.lastname: Herfindal
authors.affiliation: Department of Chemistry and Centre for Pharmacy, University of Bergen, Allégt. 41, N-5007 Bergen, Norway.
authors.forename: Ole Johan
authors.initials: OJ
authors.lastname: Juvik
authors.affiliation: Department of Biomedicine, University of Bergen, Norway.
authors.forename: Anni
authors.initials: A
authors.lastname: Vedeler
authors.affiliation: Department of Clinical Science and Centre for Pharmacy, University of Bergen, Norway.
authors.forename: Svein
authors.initials: S
authors.lastname: Haavik
authors.affiliation: Department of Chemistry and Centre for Pharmacy, University of Bergen, Allégt. 41, N-5007 Bergen, Norway. Electronic address: Torgils.Fossen@kj.uib.no.
authors.forename: Torgils
authors.initials: T
authors.lastname: Fossen
mesh_terms: D000818:Animals; D001688:Biological Products / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D003373:Coumaric Acids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D005638:Fruit / Q000737:chemistry*; D020128:Inhibitory Concentration 50; D019668:Liliaceae / Q000737:chemistry*; D015394:Molecular Structure; D011422:Propionates; D011794:Quercetin / Q000031:analogs & derivatives / Q000737:chemistry / Q000302:isolation & purification; D051381:Rats; D012756:Sheep; D013237:Stereoisomerism
chemical_list: D001688:Biological Products; D003373:Coumaric Acids; D011422:Propionates; C065497:3,7-dimethoxy-5,3',4'-trihydroxyflavone; D011794:Quercetin; C495469:p-coumaric acid
keywords: (E)-4-(3-hydroxy-2,2-dimethylchroman-6-yl)but-3-en-2-one; (E)-4-(4-(((E)-4-hydroxy-3-methylbut-2-en-1-yl)oxy)phenyl)but-3-en-2-one; 2,6-Dimethoxy cinnamic acid; Cytotoxicity; Fruits; Fungal metabolite; Liovil 4-O-β-glucopyranoside; Naringenin(3 → 6″)chrysoeriol; Naringenin(3 → 6″)luteolin; Nartheciaceae; Narthecium ossifragum