title: Silvestrol and episilvestrol, potential anticancer rocaglate derivatives from Aglaia silvestris.
abstract: Two cytotoxic rocaglate derivatives possessing an unusual dioxanyloxy unit, silvestrol (1) and episilvestrol (2), were isolated from the fruits and twigs of Aglaia silvestris by bioassay-guided fractionation monitored with a human oral epidermoid carcinoma (KB) cell line. Additionally, two new baccharane-type triterpenoids, 17,24-epoxy-25-hydroxybaccharan-3-one (3) and 17,24-epoxy-25-hydroxy-3-oxobaccharan-21-oic acid (4), as well as eleven known compounds, 1beta,6alpha-dihydroxy-4(15)-eudesmene (5), ferulic acid (6), grasshopper ketone (7), apigenin, cabraleone, chrysoeriol, 1beta,4beta-dihydroxy-6alpha,15alpha-epoxyeudesmane, 4-hydroxy-3-methoxyacetophenone, 4-hydroxyphenethyl alcohol, ocotillone, and beta-sitosterol 3-O-beta-D-glucopyranoside, were also isolated and characterized. The structures of compounds 1-4 were elucidated by spectroscopic studies and by chemical transformation. The absolute stereochemistry of silvestrol (1) was established by a X-ray diffraction study of its di-p-bromobenzoate derivative, and the structure of 3 was also confirmed by single-crystal X-ray diffraction. The isolates and chemical transformation products were evaluated for cytotoxicity against several human cancer cell lines, and silvestrol (1) and episilvestrol (2) exhibited potent in vitro cytotoxic activity. Silvestrol (1) was further evaluated in vivo in the hollow fiber test and in the murine P-388 leukemia model.
authors.affiliation: Program for Collaborative Research in the Pharmaceutical Sciences, University of Illinois at Chicago, Chicago, Illinois 60612, USA.
authors.forename: Bang Yeon
authors.initials: BY
authors.lastname: Hwang
authors.forename: Bao-Ning
authors.initials: BN
authors.lastname: Su
authors.forename: Heebyung
authors.initials: H
authors.lastname: Chai
authors.forename: Qiuwen
authors.initials: Q
authors.lastname: Mi
authors.forename: Leonardus B S
authors.initials: LB
authors.lastname: Kardono
authors.forename: Johar J
authors.initials: JJ
authors.lastname: Afriastini
authors.forename: Soedarsono
authors.initials: S
authors.lastname: Riswan
authors.forename: Bernard D
authors.initials: BD
authors.lastname: Santarsiero
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Mesecar
authors.forename: Robert
authors.initials: R
authors.lastname: Wild
authors.forename: Craig R
authors.initials: CR
authors.lastname: Fairchild
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Vite
authors.forename: William C
authors.initials: WC
authors.lastname: Rose
authors.forename: Norman R
authors.initials: NR
authors.lastname: Farnsworth
authors.forename: Geoffrey A
authors.initials: GA
authors.lastname: Cordell
authors.forename: John M
authors.initials: JM
authors.lastname: Pezzuto
authors.forename: Steven M
authors.initials: SM
authors.lastname: Swanson
authors.forename: A Douglas
authors.initials: AD
authors.lastname: Kinghorn
mesh_terms: D031602:Aglaia / Q000737:chemistry*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D004730:Endothelium, Vascular / Q000187:drug effects; D006801:Humans; D007624:KB Cells; D007941:Leukemia P388; D051379:Mice; D015394:Molecular Structure; D014315:Triterpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D001572:Benzofurans
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D014315:Triterpenes; C489893:episilvestrol; C489897:silvestrol; D001572:Benzofurans