Design, synthesis and biological evaluation of novel stilbene-based methoxycoumarins: identification of novel proapoptotic agents

The naturally occurring coumarins and resveratrol, attract great attention due to their wide range of bio- logical properties, including anticancer, antileukemic, antibacterial and anti-inflammatory activities; moreover, their cancer chemopreventive property have been recently emphasized. A novel class of hybrid compounds, obtained by introducing a substituted trans-vinylbenzene moiety on a coumarin backbone, was synthesized and evaluated for the antitumor profile. A number of derivatives showed a good antipro- liferative activity, in some cases higher to that of the reference compound resveratrol. The most promis- ing compounds in this series were 14 and 17, endowed with excellent antiproliferative and proapoptotic activities. The present study suggests that the 7-methoxycoumarin nucleus, together with the 3,5-disub- stitution pattern of the trans-vinylbenzene moiety, are likely promising structural features to obtain excellent antitumor compounds endowed with a apoptosis-inducing capability.