Ubiquitin-Proteasome Modulating Dolabellanes and Secosteroids from Soft Coral Clavularia flava.

Che-Yen Chiu,Xue-Hua Ling,Chang-Yih Duh,Shang-Kwei Wang

doi:10.3390/md18010039

Che-Yen Chiu, Xue-Hua Ling + Show 2 more

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https://doi.org/10.3390/md18010039

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Abstract

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 Clavularia flava, which potentiates proteasome inhibition. Chemical structure elucidation revealed they are dolabellane- and secosteroid-based compounds including a new dolabellane, clavinflol C (1), three known dolabellanes, stolonidiol (2), stolonidiol-17-acetate (3), and clavinflol B (4) as well as two new secosteroids, 3β,11-dihydroxy-24-methyl-9,11-secocholest-5-en-9,23-dione (5) and 3β,11-dihydroxy-24-methylene-9,11-secocholest-5-en-9,23-dione (6). 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.

Highlights

Marine natural products harbor unique chemical structures and exhibit diverse biological activity with potential therapeutic utilities that merit investigation [1]
We postulate that proteasome inhibitors may benefit the ecosystem of soft coral reef holobiont
We continued the drug screening in an effort to identify marine natural products purified from Formosan soft corals in our laboratory

Summary

Introduction

Marine natural products harbor unique chemical structures and exhibit diverse biological activity with potential therapeutic utilities that merit investigation [1]. Our initial efforts identified four natural products of soft corals cembrane-based compounds (sarcophytonin A, sarcophytoxide, sarcophine, and laevigatol A) which potentiate proteasome inhibition [4]. We postulate that proteasome inhibitors may benefit the ecosystem of soft coral reef holobiont. We continued the drug screening in an effort to identify marine natural products purified from Formosan soft corals in our laboratory. We demonstrated the identification of six compounds with proteasome inhibitory activity. Structure elucidation revealed they are dolabellane- and secosteroid-based compounds including a new dolabellane, clavinflol

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