Synthesis and cytotoxic activity of diosgenyl saponin analogues.
Diosgenyl saponins are steroidal glycosides that are often found as major components in many traditional oriental medicines. Recently, a number of naturally occurring diosgenyl saponins have been shown to exert cytotoxic activity against several strains of human cancer cells. Use of these saponin compounds for cancer treatment is hampered due to the lack of understanding of their action mechanism as well as limited access to such structurally complicated molecules. In the present paper, we have prepared a group of diosgenyl saponin analogues which contain a beta-D-2-amino-2-deoxy-glucopyranose residue having different substituents at the amino group. Moderate cytotoxic activity is found for most analogues against neuroblastoma (SK-N-SH) cells, breast cancer (MCF-7) cells, and cervical cancer (HeLa) cells. The analogue 13 that contains an alpha-lipoic acid residue exhibits the highest potency against all three cancer cell lines with IC(50) ranging from 4.8 microM in SK-N-SH cells to 7.3 microM in HeLa cells. Preliminary mechanistic investigation with one saponin analogue (10) shows that the compound induces cell cycle arrest at G(1) phase in SK-N-SH cells, but the same compound induces cell cycle arrest at G(2) phase in MCF-7 cells. This result suggests that the cytotoxic activity of these saponin analogues may involve different action mechanisms in cell lines derived from different cancer sites.
Kaskiw
Matthew J
MJ
Department of Chemistry, Lakehead University, 955 Oliver Road, Thunder Bay, Ont., Canada P7B 5E1.
Tassotto
Mary Lynn
ML
Th'ng
John
J
Jiang
Zi-Hua
ZH
D002453:Cell Cycle / Q000187:drug effects; D016923:Cell Death; D045744:Cell Line, Tumor; D004144:Diosgenin / Q000031:analogs & derivatives*; D016193:G1 Phase; D016195:G2 Phase; D006801:Humans; D020128:Inhibitory Concentration 50; D012503:Saponins / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
D012503:Saponins; D004144:Diosgenin