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.
Jung
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Department of Pharmaceutical Chemistry, Westfälische Wilhelms-Universität Münster, Germany. jungm@unimuenster.de
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Elson
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D000438:Alcohols; D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D018890:Chemoprevention; D008546:Melanoma, Experimental / Q000517:prevention & control*; D051379:Mice; D045792:Norisoprenoids; D013329:Structure-Activity Relationship; D013729:Terpenes / Q000737:chemistry / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000438:Alcohols; D000970:Antineoplastic Agents; D045792:Norisoprenoids; D013729:Terpenes; C008157:beta-ionone