Cytotoxic oleanane triterpenoid saponins from Albizia julibrissin

Bioassay-guided fractionation of the ethanolic extract of the stem bark of Albizia julibrissin led to the isolation of ten new oleanane-type triterpenoid saponins, julibrosides J(37)-J(48) (1-10), along with six known analogues (11-16). In addition, 11 prosapogenins (17-27) were prepared by mild or strong alkaline hydrolysis of the total saponin. The structures of 1-27 were determined by spectroscopic and chemical means, and their cytotoxicities against four human cancer cell lines, BGC-823, A549, HCT-116, and HepG2 were evaluated. Compounds 5-16 exhibited significant inhibitory activity with IC50 values ranging from 2.59 to 9.30 mu M, and 8 turned out to be the most active compound with all IC50 values < 5 mu M. A preliminary structure-activity relationship of these saponins clearly indicated that the outer monoterpenoid moiety (MT') is a crucial substituent for cytotoxicity, and the linkage sites of the MT' unit greatly influenced the activity. It could also be inferred that the existence of 16-OH of the aglycone almost has no effect on cytotoxicity and the N-acetyl-glucosamine moiety at C-3 seems to enhance activity.