Structural analogues of diosgenyl saponins: synthesis and anticancer activity.
Saponins display various biological activities including anti-tumor activity. Recently intensive research has been focused on developing saponins for tumor therapies. The diosgenyl saponin dioscin is one of the most common steroidal saponins and exhibits potent anticancer activity in several human cancer cells through apoptosis-inducing pathways. In this paper, we describe the synthesis of several diosgenyl saponin analogues containing either a 2-amino-2-deoxy-beta-d-glucopyranosyl residue or an alpha-l-rhamnopyranosyl-(1-->4)-2-amino-2-deoxy-beta-d-glucopyranosyl residue with different acyl substituents on the amino group. The cytotoxic activity of these compounds was evaluated in MCF-7 breast cancer cells and HeLa cervical cancer cells. Structure-activity relationship studies show that the disaccharide saponin analogues are in general less active than their corresponding monosaccharide analogues. The incorporation of an aromatic nitro functionality into these saponin analogues does not exhibit significant effect on their cytotoxic activity.
Kaskiw
Matthew J
MJ
Department of Chemistry, Lakehead University, 955 Oliver Road, Thunder Bay, ON, Canada P7B 5E1.
Tassotto
Mary Lynn
ML
Mok
Mac
M
Tokar
Stacey L
SL
Pycko
Roxanne
R
Th'ng
John
J
Jiang
Zi-Hua
ZH
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004144:Diosgenin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004187:Disaccharides / Q000737:chemistry; D005260:Female; D006367:HeLa Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D009005:Monosaccharides / Q000737:chemistry; D012503:Saponins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002583:Uterine Cervical Neoplasms / Q000378:metabolism / Q000473:pathology
D000970:Antineoplastic Agents; D004187:Disaccharides; D009005:Monosaccharides; D012503:Saponins; D004144:Diosgenin