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Tigliane glycosides from Euphorbia tirucalli as multidrug resistance modulators
Lan-Jun Zhang1, Kai-Bo Wang2, Ke-Jing Li3
1State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou 730000, People's Republic of China; Tea Research Institute, Yunnan Academy of Agricultural Science, Kunming 650201, People's Republic of China.
Abstract:
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.
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