title: Structural analogues of diosgenyl saponins: synthesis and anticancer activity.
abstract: 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.
authors.affiliation: Department of Chemistry, Lakehead University, 955 Oliver Road, Thunder Bay, ON, Canada P7B 5E1.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Kaskiw
authors.forename: Mary Lynn
authors.initials: ML
authors.lastname: Tassotto
authors.forename: Mac
authors.initials: M
authors.lastname: Mok
authors.forename: Stacey L
authors.initials: SL
authors.lastname: Tokar
authors.forename: Roxanne
authors.initials: R
authors.lastname: Pycko
authors.forename: John
authors.initials: J
authors.lastname: Th'ng
authors.forename: Zi-Hua
authors.initials: ZH
authors.lastname: Jiang
mesh_terms: 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
chemical_list: D000970:Antineoplastic Agents; D004187:Disaccharides; D009005:Monosaccharides; D012503:Saponins; D004144:Diosgenin