Silvestrol and episilvestrol, potential anticancer rocaglate derivatives from Aglaia silvestris.
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.
Hwang
Bang Yeon
BY
Program for Collaborative Research in the Pharmaceutical Sciences, University of Illinois at Chicago, Chicago, Illinois 60612, USA.
Su
Bao-Ning
BN
Chai
Heebyung
H
Mi
Qiuwen
Q
Kardono
Leonardus B S
LB
Afriastini
Johar J
JJ
Riswan
Soedarsono
S
Santarsiero
Bernard D
BD
Mesecar
Andrew D
AD
Wild
Robert
R
Fairchild
Craig R
CR
Vite
Gregory D
GD
Rose
William C
WC
Farnsworth
Norman R
NR
Cordell
Geoffrey A
GA
Pezzuto
John M
JM
Swanson
Steven M
SM
Kinghorn
A Douglas
AD
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
D000972:Antineoplastic Agents, Phytogenic; D014315:Triterpenes; C489893:episilvestrol; C489897:silvestrol; D001572:Benzofurans