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Peumusolide A, unprecedented NES non-antagonistic inhibitor for nuclear export of MEK |
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| Authors: | Satoru Tamura Masafumi Kaneko Susumu Tanimura Nobutoshi Murakami |
| Affiliation: | a Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka 565-0871, Japan b PRESTO, Japan Science and Technology Agency (JST), 4-1-8 Honcho Kawaguchi, Saitama 332-0012, Japan c Graduate School of Biomedical Sciences, Nagasaki University, 1-14 Bunkyo-machi Nagasaki 852-8521, Japan |
| Abstract: | A new polyketide peumusolide A was disclosed as an unprecedented NES non-antagonistic inhibitor for nuclear export of MEK, a promising scaffold for antitumor agents with novel mechanism of action, from Peumus boldus Molina. The absolute stereostructure as well as optical purity was established by use of the two synthesized enantiomeric model lactones. In addition, the Δε values in their CD spectra were demonstrated to be the conclusive index for determination of not only configuration at C-3 but also optical purity of natural congeneric polyketides. Peumusolide A was revealed to show NES non-antagonistic action by the biotinylated probe and to inhibit proliferation of MEK-activated tumor cells selectively. |
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