title: Watsonianone A-C, anti-plasmodial β-triketones from the Australian tree, Corymbia watsoniana.
abstract: Three new β-triketones, watsonianones A-C, and the known compound corymbone B were isolated from the flowers of the Australian eucalypt Corymbia watsoniana. Watsonianone A is the first naturally occurring methylene bridged bis-tetramethylcyclohexatrione, watsonianone B is only the fourth fused bisfurano β-triketone and watsonianone C is the first 4,4a,9,9a-tetrahydro-2H-xanthene-1,3,5,7(6H,8H)-tetraone to be reported in the literature. MS and NMR analysis established the structures of the new compounds. All three new compounds showed anti-plasmodial activity against chloroquine resistant (Dd2) and sensitive strains (3D7) of the parasite, Plasmodium falciparum, responsible for malarial infections. Watsonianone B was the most potent inhibitor (IC(50) 0.289 μM vs. Pf 3D7) demonstrating significant selectivity against the human cell line, HEK 293 (>400 ×). Stage specificity studies indicate that watsonianone B is predominantly active against young ring stages of P. falciparum.
authors.affiliation: Environmental Futures Centre, Griffith University, Gold Coast, QLD 4222, Australia. a.carroll@griffith.edu.au
authors.forename: Anthony R
authors.initials: AR
authors.lastname: Carroll
authors.forename: Vicky M
authors.initials: VM
authors.lastname: Avery
authors.forename: Sandra
authors.initials: S
authors.lastname: Duffy
authors.forename: Paul I
authors.initials: PI
authors.lastname: Forster
authors.forename: Gordon P
authors.initials: GP
authors.lastname: Guymer
mesh_terms: D000962:Antimalarials / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D003512:Cyclohexanones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D035264:Flowers / Q000737:chemistry; D005663:Furans / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D057809:HEK293 Cells; D006801:Humans; D008968:Molecular Conformation; D027822:Myrtaceae / Q000737:chemistry*; D021261:Parasitic Sensitivity Tests; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D010963:Plasmodium falciparum / Q000187:drug effects*; D013329:Structure-Activity Relationship; D014966:Xanthenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*
chemical_list: D000962:Antimalarials; D003512:Cyclohexanones; D005663:Furans; D010936:Plant Extracts; D014966:Xanthenes; C584688:watsonianone A; C584690:watsonianone B; C584689:watsonianone C