Functional cell-based screening and saturation transfer double-difference NMR have identified haplosamate A as a...

A marine natural product extract library has been screened with a functional cell-based G-protein coupled receptor assay to find compounds capable of binding the human cannabinoid receptors CB1 and CB2. The methanol extract of the marine sponge Dasychalina fragilis collected in Papua New Guinea was active in the assay. Bioassay-guided fractionation of the extract identified the phosphorylated sterol sulfate haplosamate A (1) as a cannabinoid receptor agonist. The high water solubility of haplosamate A (1) allowed exploration of its binding interactions with the human cannabinoid receptors in whole insect cells by means of saturation transfer double-difference NMR spectroscopy. This technique confirmed that haplosamate A (1) binds selectively to these receptors.