title: New cardenolide glycosides from the seeds of Digitalis purpurea and their cytotoxic activity.
abstract: A chemical investigation of Digitalis purpurea seeds led to the isolation of three new cardenolide glycosides (1, 8 and 11), together with 12 known cardenolide glycosides (2-7, 9, 10 and 12-15). The structures of 1, 8 and 11 were determined by 1D and 2D NMR spectroscopic analyses and the results of an acid or enzymatic hydrolysis. The cytotoxic activity of the isolated compounds (1-15) against HL-60 leukemia cells was examined. Compounds 2, 9, 11 and 12 showed potent cytotoxicity against HL-60 cells with respective 50% inhibition concentration (IC50) values of 0.060, 0.069, 0.038, and 0.034 µM. Compounds 2, 9 and 11 also exhibited potent cytotoxic activity against HepG2 human liver cancer cells with respective IC50 values of 0.38, 0.79, and 0.71 µM. An investigation of the structure-activity relationship showed that the cytotoxic activity was reduced by the introduction of a hydroxy group at C-16 of the digitoxigenin aglycone, methylation of the C-3' hydroxy group at the fucopyranosyl moiety, and acetylation of the C-3' hydroxy group at the digitoxopyranoyl moiety.
authors.affiliation: Department of Medicinal Pharmacognosy, Tokyo University of Pharmacy and Life Sciences, School of Pharmacy, Tokyo, Japan. kurodam@toyaku.ac.jp
authors.forename: Minpei
authors.initials: M
authors.lastname: Kuroda
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kubo
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Matsuo
authors.forename: Tomomi
authors.initials: T
authors.lastname: Atou
authors.forename: Junichi
authors.initials: J
authors.lastname: Satoh
authors.forename: Tomofumi
authors.initials: T
authors.lastname: Fujino
authors.forename: Makio
authors.initials: M
authors.lastname: Hayakawa
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Mimaki
mesh_terms: D002298:Cardenolides / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor / Q000187:drug effects*; D004071:Digitalis Glycosides / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D012639:Seeds / Q000737:chemistry
chemical_list: D002298:Cardenolides; D004071:Digitalis Glycosides; D010936:Plant Extracts