Silvestrol and episilvestrol, potential anticancer rocaglate derivatives from Aglaia silvestris
Silvestrol and episilvestrol, potential anticancer rocaglate derivatives from Aglaia silvestris
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DOI：
10.1021/jo040120f
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发表时间：
2004-05-14
影响因子：
3.6
通讯作者：
Kinghorn, AD
中科院分区：
文献类型：
--
作者：
Hwang, BY;Su, BN;Kinghorn, AD
两种具有不寻常的二氧杂环己烷氧基单元的细胞毒性罗卡酸酯衍生物，silvestrol（1）和episilvestrol（2），通过生物测定指导的分级分离，从米仔兰的果实和树枝中分离出来，与人口腔表皮样癌（KB）细胞系监测。此外，还发现了两种新的baccharane型三萜类化合物，17，24-环氧-25-羟基baccharan-3-酮（3）和17，24-环氧-25-羟基-3-氧代baccharan-21-酸（4），以及11种已知化合物，1 β，6 α-二羟基-4（15）-桉叶烯（5）、阿魏酸（6）、蚱蜢酮（7）、芹菜素、cabraleone、chrysoeriol、1 β，4 β-二羟基-6 α，还分离和表征了15 α-环氧去甲肾上腺素、4-羟基-3-甲氧基苯乙酮、4-羟基苯乙醇、ocotillone和β-谷甾醇3-O-β-D-吡喃葡萄糖苷。化合物1-4的结构经波谱学和化学转化法鉴定。通过对西维司群的二对溴苯甲酸酯衍生物的X射线衍射研究，确定了西维司群（1）的绝对立体化学，并通过单晶X射线衍射证实了3的结构。评价了分离物和化学转化产物对几种人癌细胞系的细胞毒性，并且司维司酚（1）和表司维司酚（2）表现出有效的体外细胞毒性活性。在中空纤维试验和鼠P-388白血病模型中进一步评价了司维司群（1）。
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.