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

**Che-Yen Chiu 1,**†**, Xue-Hua Ling 1,**†**, Shang-Kwei Wang 2,\* and Chang-Yih Duh 1,\***


Received: 10 December 2019; Accepted: 30 December 2019; Published: 3 January 2020

**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.

**Keywords:** proteasome inhibition; dolabellane; secosteroids; soft coral
