Meroterpenes from Dichrostachys cinerea inhibit protein farnesyl transferase activity.
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.
Long
Christophe
C
Joint Service Unit No. 2597, National Center for Scientific Research (CNRS)-Pierre Fabre, Sciences and Technologies Institute of Medicine of Toulouse, 31432 Toulouse, France.
Marcourt
Laurence
L
Raux
Roselyne
R
David
Bruno
B
Gau
Christelle
C
Menendez
Christophe
C
Gao
Min
M
Laroche
Marie-France
MF
Schambel
Philippe
P
Delaude
Clément
C
Ausseil
Frédéric
F
Lavaud
Catherine
C
Massiot
Georges
G
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*
D013729:Terpenes; D019883:Alkyl and Aryl Transferases; C064911:p21(ras) farnesyl-protein transferase