We performed a high-content screening (HCS) assay aiming to discover bioactive molecules with proteasome inhibitory activity. By structural elucidation, we identified six compounds purified from soft coral , which potentiates proteasome inhibition Chemical structure elucidation revealed they are dolabellane- and secosteroid-based compounds including a new dolabellane, clavinflol C (), three known dolabellanes, stolonidiol (), stolonidiol-17-acetate (), and clavinflol B () as well as two new secosteroids, 3,11-dihydroxy-24-methyl-9,11-secocholest-5-en-9,23-dione () and 3,11-dihydroxy-24-methylene-9,11-secocholest-5-en-9,23-dione (). All six compounds show less cytotoxicity than those of known proteasome inhibitors, bortezomib and MG132. In summary, the high-content measurements of control inhibitors, bortezomib and MG132, manifest the highest ratio >2 in high-content measurement. Of the isolated compounds, 2 and 5 showed higher activity, followed by 3 and 6, and then 1 and 4 exhibited moderate inhibition.
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| http://dx.doi.org/10.3390/md18010039 | DOI Listing |
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