title: Proteasome inhibitors from Neoboutonia melleri.
abstract: Thirty new cycloartane derivatives (1-3, 5-12, 14-32) have been isolated from the leaves of Neoboutonia melleri. Their novelty stems from the loss of one of the C-4 methyl groups (1-3, 5-12, 14-25, and 32) and from the presence of an "extra" carbon atom in the side chain (1-3, 5-12, 14-20, 26-29, and 30-32). Furthermore, compound 32 possesses a rare triterpene skeleton with the cyclopropane ring fused onto C-1 and C-10, instead of C-9 and C-10. The structures were determined by spectrometric means, chemical correlations, and X-ray crystallography of derivative 1c. The substitution pattern in ring A, with a cyclopropyl ring conjugated with an α,β-unsaturated carbonyl moiety, confers to the molecule a particular reactivity, giving rise to a formal inversion of the stereochemistry of the cyclopropane ring under UV irradiation. These compounds showed an interesting level of activity on the proteasome pathway, thus motivating their evaluation as possible anticancer agents. The large number of isolated compounds permitted a structure-activity relationship analysis, which showed that the presence of the two enone functions was a requirement for the activity.
authors.affiliation: USR CNRS-Pierre Fabre No. 3388 ETaC, Centre de Recherche et Développement Pierre Fabre, 3 Avenue Hubert Curien, 31035 Toulouse Cedex 01, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Long
authors.forename: Joséphine
authors.initials: J
authors.lastname: Beck
authors.forename: Frédéric
authors.initials: F
authors.lastname: Cantagrel
authors.forename: Laurence
authors.initials: L
authors.lastname: Marcourt
authors.forename: Laure
authors.initials: L
authors.lastname: Vendier
authors.forename: Bruno
authors.initials: B
authors.lastname: David
authors.forename: Fabien
authors.initials: F
authors.lastname: Plisson
authors.forename: Fadila
authors.initials: F
authors.lastname: Derguini
authors.forename: Isabelle
authors.initials: I
authors.lastname: Vandenberghe
authors.forename: Yannick
authors.initials: Y
authors.lastname: Aussagues
authors.forename: Frédéric
authors.initials: F
authors.lastname: Ausseil
authors.forename: Catherine
authors.initials: C
authors.lastname: Lavaud
authors.forename: François
authors.initials: F
authors.lastname: Sautel
authors.forename: Georges
authors.initials: G
authors.lastname: Massiot
mesh_terms: D002163:Cameroon; D019665:Euphorbiaceae / Q000737:chemistry*; D015394:Molecular Structure; D018515:Plant Leaves / Q000737:chemistry; D018547:Plant Stems / Q000737:chemistry; D061988:Proteasome Inhibitors; D013329:Structure-Activity Relationship; D014315:Triterpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*
chemical_list: D061988:Proteasome Inhibitors; D014315:Triterpenes; C085352:cycloartane