Tigliane glycosides from Euphorbia tirucalli as multidrug resistance modulators.

Chemical investigation of the twigs and leaves of Euphorbia tirucalli afforded six undescribed tigliane glycosides, tirucalosides A-F (1-6), together with 12 known diterpenoids (7-18). Compound 1 represents a rare carbon skeleton bearing a 5/7/5/4-fused ring system, while compound 6 contains an unusual seco-glucoside substitution. Their structures were determined by a combination of an extensive spectroscopic analysis and acid hydrolysis experiment. Compounds 1-5 reversed multidrug resistance on adriamycin-resistant K562/ADR cells with the fold-reversals ranging from 17.4 to 64.6 at the noncytotoxic concentration of 10 μM. The rhodamine 123 efflux assays revealed that compound 1 inhibited the P-glycoprotein (P-gp) transporter function, thus reversing the drug resistance.