Nitrogen-containing dihydro-β-agarofuran derivatives and macrocyclic spermidine alkaloids with anti-tumor activity from the stems of Tripterygium wilfordii.

A total of eight nitrogen-containing dihydro-β-agarofuran derivatives (1-8), seven of which (2-8) are new compounds, together with four known 13-membered macrocyclic spermidine alkaloids (9-12), were isolated from aqueous ethanol extracts of the dried stems of Tripterygium wilfordii. These compounds were evaluated for their in vitro inhibitory activities against several cancer cell lines. Nitrogen-containing dihydro-β-agarofuran derivatives exhibited very weak inhibitory activities, while 13-membered macrocyclic spermidine alkaloids displayed differential effects. Notably, the IC50 values of celacarfurine in 72 h on MCF-7, AFC, AGS, RL95-2 and AN3 CA cell lines were 14.33, 8.36, 9.40, 11.97 and 21.92 μM, respectively. In addition, celacarfurine and celafurine exhibited synergistic effects on 5-fluorouracil-resistant HCT116 cell model. The calculate combination indexes of 40 μM celacarfurine and 200 μM celafurine against this model were 0.50 and 0.66, respectively. The potent anti-tumor activity of celacarfurine is likely to be attributed to hydrogen-bonding interactions formed by the three amide moieties within its 13-membered macrocyclic scaffold.