Antimalarial (+)-trans-hexahydrodibenzopyran derivatives from Machaerium multiflorum

Bioassay-guided fractionation of Machaerium multiflorum yielded the hithert o unreported (+)-trans-hexahydrodibenzopyrans machaeriol. A (1) and machaer iol B (2), as well as the known guaiane sesquiterpene (-)-kessane. Structur e elucidation was based on H-1 and C-13 NMR data, mainly 2D NMR H-1-H-1 COS Y, H-1-C-13 HMQC, H-1-C-13 HMBC, and H-1-H-1 NOESY experiments. This is the first report of the hexahydrodibenzopyrans from a higher plant other than the genus Cannabis. The cannabimimetic activity was thus evaluated by radio ligand binding assay for cannabinoid receptor CB1, which indicated, notably , that both 1 and 2 were inactive. In addition, the cross reactivity of I a nd 2 toward antibodies designed for urinary metabolites of cannabinoids was evaluated with the EMIT and On Line cannabinoids; assays. Both compounds s howed no response at 100 000 ng/mL in both assays. Machaeriol B (2) demonst rated in vitro antimalarial activity (IC50 = 120 ng/mL) against Plasmodium falciparum W-2 clone.