Watsonianone A-C, anti-plasmodial β-triketones from the Australian tree, Corymbia watsoniana

Org Biomol Chem. 2013 Jan 21;11(3):453-8. doi: 10.1039/c2ob26931g. Epub 2012 Nov 29.

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.

MeSH terms

  • Antimalarials / chemistry
  • Antimalarials / isolation & purification
  • Antimalarials / pharmacology*
  • Cell Survival / drug effects
  • Cyclohexanones / chemistry
  • Cyclohexanones / isolation & purification
  • Cyclohexanones / pharmacology*
  • Dose-Response Relationship, Drug
  • Flowers / chemistry
  • Furans / chemistry
  • Furans / isolation & purification
  • Furans / pharmacology*
  • HEK293 Cells
  • Humans
  • Molecular Conformation
  • Myrtaceae / chemistry*
  • Parasitic Sensitivity Tests
  • Plant Extracts / chemistry
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology
  • Plasmodium falciparum / drug effects*
  • Structure-Activity Relationship
  • Xanthenes / chemistry
  • Xanthenes / isolation & purification
  • Xanthenes / pharmacology*

Substances

  • Antimalarials
  • Cyclohexanones
  • Furans
  • Plant Extracts
  • Xanthenes
  • watsonianone A
  • watsonianone B
  • watsonianone C