Meroterpenes from Dichrostachys cinerea Inhibit Protein Farnesyl Transferase Activity

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• 作者：Christophe Long ; Laurence Marcourt ; Roselyne Raux ; Bruno David ; Christelle Gau ; Christophe Menendez ; Min Gao ; Marie-France Laroche ; Philippe Schambel ; Clment Delaude ; Frdric Ausseil ; Catherine Lavaud
• 刊名：Journal of Natural Products
• 出版年：2009
• 出版时间：October 23, 2009
• 年：2009
• 卷：72
• 期：10
• 页码：1804-1815
• 全文大小：360K
• 年卷期：v.72,no.10(October 23, 2009)
• ISSN：1520-6025

文摘

Eighteen new meroterpene derivatives, dichrostachines A−R (1−18), have been isolated from the root and stem barks of Dichrostachys cinerea, and their structures determined by spectroscopic means and molecular modeling. From a biosynthetic standpoint these compounds arise from a Diels−Alder reaction between a labdane diene of the raimonol type and a flavonoid B-ring-derived quinone. The hypothesis was tested by the partial synthesis of similar compounds by simply mixing methyl communate and a synthetic flavonoid quinone. The hemisynthetic compounds were shown by NMR to have configurations different from those of the natural products, thus allowing a refinement of the biosynthesis hypothesis. Most of the compounds were assayed for their ability to inhibit the enzyme protein farnesyl transferase. The most active compounds exhibited IC₅₀ and cytotoxicity values in the 1 μM range.