Synthesis and evaluation of novel anti-proliferative pyrroloazepinone and indoloazepinone oximes derived from the marine natural product hymenialdisine

The tetrahydroazepinone pharmacophore is a component of many interesting compounds, including several marine natural products, with anti-cancer properties. The synthesis and biological evaluation of a novel series of pyrroloazepinone and indoloazepinone oximes is reported. These compounds showed promising growth inhibition activity against four human cancer cell lines but did not significantly inhibit the cell cycle regulator cyclin dependent kinase 2. The most active compounds in this series displayed improved anti-proliferative activity over the related synthetic indoloazepine kenpaullone. The structure activity relationships exhibited by the azepinone pharmacophore suggests several novel lead compounds for anti-cancer drug discovery.

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► Marine natural products are important lead compounds for drug discovery.
► Novel derivatives of the marine natural product hymenialdisine are reported.
► The tetrahydroazepinone pharmacophore from hymenialdisine has been developed.
► Pyrroloazepinones and indoloazepine oximes have anti-proliferative activity.