title: Facile synthesis of triterpenoid saponins bearing β-Glu/Gal-(1→3)-β-GluA methyl ester and their cytotoxic activities.
abstract: Convenient synthetic strategy toward spinasaponin A methyl ester 1 and calenduloside G methyl ester 2, two natural oleanane-type triterpenoid saponins bearing an unique β-D-glucosyl/galactosyl-(1→3)-β-D-glucuronic acid methyl ester disaccharide moiety, was established. Based on this facile approach, four structurally modified congeners 3-6 with ursolic acid and glycyrrhetinic acid as aglycones were efficiently synthesized. MTT assay revealed the cytotoxicities against cancer cells of the synthesized saponins were varied with the change of aglycones and sugar units. Saponin 2 possessing the most potent cytotoxic effects could induce apoptosis of MCF-7 cells, which was detected by confocal micrographs using DAPI staining and flow cytometry using Annexin V and PI double staining. Furthermore, 2-induced apoptosis in MCF-7 cells was associated with ROS generation and loss of the mitochondria membrane potential (Δψ(m)).
authors.affiliation: Department of Natural Product Chemistry, School of Pharmaceutical Sciences, Shandong University, 44 West Wenhua Road, Jinan 250012, PR China.
authors.forename: Jian
authors.initials: J
authors.lastname: Gao
authors.forename: Xia
authors.initials: X
authors.lastname: Li
authors.forename: Guofeng
authors.initials: G
authors.lastname: Gu
authors.forename: Shanshan
authors.initials: S
authors.lastname: Liu
authors.forename: Min
authors.initials: M
authors.lastname: Cui
authors.forename: Hong-Xiang
authors.initials: HX
authors.lastname: Lou
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004187:Disaccharides / Q000737:chemistry; D005434:Flow Cytometry; D006034:Glycyrrhetinic Acid / Q000737:chemistry; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism; D012503:Saponins / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013778:Tetrazolium Salts; D013844:Thiazoles; D014315:Triterpenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000097245:Ursolic Acid
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004187:Disaccharides; D006034:Glycyrrhetinic Acid; D017382:Reactive Oxygen Species; D012503:Saponins; D013778:Tetrazolium Salts; D013844:Thiazoles; D014315:Triterpenes; D000097245:Ursolic Acid; C022616:thiazolyl blue