Bioorganic & Medicinal Chemistry 2010-06-01

Simple di- and trivanillates exhibit cytostatic properties toward cancer cells resistant to pro-apoptotic stimuli.

Delphine Lamoral-Theys, Laurent Pottier, Frédéric Kerff, François Dufrasne, Fabien Proutière, Nathalie Wauthoz, Philippe Neven, Laurent Ingrassia, Pierre Van Antwerpen, Florence Lefranc, Michel Gelbcke, Bernard Pirotte, Jean-Louis Kraus, Jean Nève, Alexander Kornienko, Robert Kiss, Jacques Dubois

Index: Bioorg. Med. Chem. 18 , 3823-33, (2010)

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Abstract

A series of 33 novel divanillates and trivanillates were synthesized and found to possess promising cytostatic rather than cytotoxic properties. Several compounds under study decreased by >50% the activity of Aurora A, B, and C, and WEE1 kinase activity at concentrations <10% of their IC(50) growth inhibitory ones, accounting, at least partly, for their cytostatic effects in cancer cells and to a lesser extent in normal cells. Compounds 6b and 13c represent interesting starting points for the development of cytostatic agents to combat cancers, which are naturally resistant to pro-apoptotic stimuli, including metastatic malignancies.