Synthesis and biological activity of beta-ionone-derived alcohols for cancer chemoprevention

Secondary products of plant mevalonate metabolism suppress the synthesis of mevalonate, the rate-limiting intermediate in the biosynthesis of isoprenoid derived compounds that stimulate cell proliferation. They exert their inhibitory action by the suppression of the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR). They exhibit low toxicity and have proven their efficacy in animal cancer chemoprevention studies but their growth inhibitory activities leave room for improvement. We have chosen beta-ionone (1) as a lead compound for the development of more potent inhibitors of mevalonate pathways. A series of ionone-derived alcohols have been synthesized and tested on an in-vitro model system (B16F10 mouse melanoma). We have found several derivatives which show higher growth inhibitory properties and are promising candidates for further improvement of activity.