Jatrophane diterpenoids from the latex of Euphorbia dendroides and their anti-P-glycoprotein activity in human multi-drug resistant cancer cell lines

Complete blockade of P-glycoprotein by jatrophane diterpenoids from Euphorbia dendroides. [Display omitted] ► Thirteen jatrophanes were isolated from the latex of Euphorbia dendroides. ► The structures of compounds were elucidated by spectroscopic techniques. ► The P-glycoprotein activities of the representative set of jatrophanes have been assessed. ► SAR of jatrophanes from two plant locations was discussed. Thirteen jatrophane diterpenoids (1–10, 13–15), three previously isolated (11, 12, 16) and a known tigliane (17) were isolated from the latex of Euphorbia dendroides. The structures and relative configurations of compounds were elucidated by spectroscopic techniques. The P-glycoprotein (P-gp) inhibiting activities of the representative set of jatrophanes (1–6 and 11–16) have been assessed. Jatrophanes 2 and 5 demonstrated the most powerful inhibition of P-gp, higher than R(+)-verapamil and tariquidar in colorectal multi-drug resistant (MDR) cells (DLD1-TxR).