Cytotoxic and NF-魏B Inhibitory Constituents of the Stems of Cratoxylum cochinchinense and Their Semisynthetic Analogues

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• 作者：Yulin Ren ; Susan Matthew ; Daniel D. Lantvit ; Tran Ngoc Ninh ; Heebyung Chai ; James R. Fuchs ; Djaja D. Soejarto ; Esperanza J. Carcache de Blanco ; Steven M. Swanson ; A. Douglas Kinghorn
• 刊名：Journal of Natural Products
• 出版年：2011
• 出版时间：May 27, 2011
• 年：2011
• 卷：74
• 期：5
• 页码：1117-1125
• 全文大小：858K
• 年卷期：v.74,no.5(May 27, 2011)
• ISSN：1520-6025

文摘

A new caged xanthone (1), a new prenylxanthone (2), seven known xanthones, and a known sterol glucoside were isolated from the stems of Cratoxylum cochinchinense, collected in Vietnam. Compounds 1 and 2 were determined structurally by analysis of their spectroscopic data. In addition, five new (10 and 16鈭?b>19) and eight known prenylated xanthone derivatives were synthesized from the known compounds 伪-mangostin (3) and cochinchinone A (6). Several of these substances were found to be cytotoxic toward HT-29 human colon cancer cells, with the most potent being 3,6-di-O-acetyl-伪-mangostin (8, ED₅₀, 1.0 渭M), which was tested further in an in vivo hollow fiber assay, but found to be inactive at the highest dose used (20 mg/kg; ip). Of the substances evaluated in a NF-魏B p65 inhibition assay, 1,3,7-trihydroxy-2,4-diisoprenylxanthone (5) exhibited the most potent activity (IC₅₀, 2.9 渭M). In a mitochondrial transmembrane potential assay, two new compounds, 1 (IC₅₀, 3.3 渭M) and 10 (IC₅₀, 1.4 渭M), and two known compounds, 3 (伪-mangostin, IC₅₀, 0.2 渭M) and 11 (3,6-di-O-methyl-伪-mangostin, IC₅₀, 0.9 渭M), were active. A preliminary analogue development study showed that 3,6-diacetylation and 6-benzoylation both slightly increased the cytotoxicity of 伪-mangostin (3), whereas methylation reduced such activity. In contrast, neither acetylation, benzoylation, nor methylation enhanced the cytotoxicity of cochinchinone A (6).