Protein kinase inhibitors from the New Caledonian rainforest

Abstract

Some interesting features can be drawn from these chemical series. All the active compounds possess a polycyclic ring system and at least one phenol ring. The location of the hydroxy groups seems to be important for the expression of a strong inhibition. In the phenanthrenes series, the most active compound possess the hydroxy group at position C-1, whereas compounds with an hydroxyl at C-2 are less active. A hydroxyl at position C-4’ in the flavone series and at position C-6, or to a lesser extent at C-8, in the aristolactam series are essential for a strong binding affinity; only velutin (7), aristolactam AIIIa (11) and velutinam (12) possess a strong activity. In addition, the Goniothalamus species contain a second type of inhibitor with the presence of medioresinol (13), a lignan previously isolated from Eucommia ulmoides.(5) The kinase inhibiting property could explain the cytotoxicity found on KB cells for most of the active compounds, except for medioresinol (13), which is not active on KB cells at 10 μg/mL. Results Appendicula reflexa is an endemic plant growing in the South Pacific region. The genus Appendicula has never been studied but Orchidaceae have been widely investigated. Two new (1 and 6) and 4 known phenanthrenes have been isolated from the aerial part after bioassay-guided purification. Phenanthrenes are fairly distributed in higher plants, but mainly in the Orchidaceae family. The new compounds exhibited a strong inhibiting activity on the CDK1/cyclin B kinase.