title: Meroterpenes from Dichrostachys cinerea inhibit protein farnesyl transferase activity.
abstract: 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 microM range.
authors.affiliation: Joint Service Unit No. 2597, National Center for Scientific Research (CNRS)-Pierre Fabre, Sciences and Technologies Institute of Medicine of Toulouse, 31432 Toulouse, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Long
authors.forename: Laurence
authors.initials: L
authors.lastname: Marcourt
authors.forename: Roselyne
authors.initials: R
authors.lastname: Raux
authors.forename: Bruno
authors.initials: B
authors.lastname: David
authors.forename: Christelle
authors.initials: C
authors.lastname: Gau
authors.forename: Christophe
authors.initials: C
authors.lastname: Menendez
authors.forename: Min
authors.initials: M
authors.lastname: Gao
authors.forename: Marie-France
authors.initials: MF
authors.lastname: Laroche
authors.forename: Philippe
authors.initials: P
authors.lastname: Schambel
authors.forename: Clément
authors.initials: C
authors.lastname: Delaude
authors.forename: Frédéric
authors.initials: F
authors.lastname: Ausseil
authors.forename: Catherine
authors.initials: C
authors.lastname: Lavaud
authors.forename: Georges
authors.initials: G
authors.lastname: Massiot
mesh_terms: D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors*; D015023:Democratic Republic of the Congo; D007887:Fabaceae / Q000737:chemistry*; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D024301:Plant Bark / Q000737:chemistry; D010946:Plants, Medicinal / Q000737:chemistry*; D013729:Terpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*
chemical_list: D013729:Terpenes; D019883:Alkyl and Aryl Transferases; C064911:p21(ras) farnesyl-protein transferase