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: Bang Yeon Hwang, Bao-Ning Su, Heebyung Chai, Qiuwen Mi, Leonardus B S Kardono, Johar J Afriastini, Soedarsono Riswan, Bernard D Santarsiero, Andrew D Mesecar, Robert Wild, Craig R Fairchild, Gregory D Vite, William C Rose, Norman R Farnsworth, Geoffrey A Cordell, John M Pezzuto, Steven M Swanson, A Douglas Kinghorn
• Journal: The Journal of organic chemistry (J Org Chem) Vol. 69 Issue 10 Pg. 3350-8 (May 14 2004) ISSN: 0022-3263 [Print] United States
• PMID: 15132542 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antineoplastic Agents, Phytogenic
• Triterpenes
• episilvestrol
• silvestrol

Topics

• Aglaia (chemistry)
• Animals
• Antineoplastic Agents, Phytogenic (chemistry, isolation & purification, pharmacology)
• Cell Line, Tumor
• Drug Screening Assays, Antitumor
• Endothelium, Vascular (drug effects)
• Humans
• KB Cells
• Leukemia P388
• Mice
• Molecular Structure
• Triterpenes (chemistry, isolation & purification, pharmacology)