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 (IC₅₀ 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.