*Article* **Cytotoxic Thiodiketopiperazine Derivatives from the Deep Sea-Derived Fungus** *Epicoccum nigrum* **SD-388**

**Lu-Ping Chi 1,2,3, Xiao-Ming Li 1,2, Li Li 1,2,3, Xin Li 1,2,\* and Bin-Gui Wang 1,2,4,\***


Received: 8 February 2020; Accepted: 11 March 2020; Published: 13 March 2020

**Abstract:** Four new thiodiketopiperazine alkaloids, namely, 5'-hydroxy-6'-ene-epicoccin G (**1**), 7-methoxy-7'-hydroxyepicoccin G (**2**), 8'-acetoxyepicoccin D (**3**), and 7'-demethoxyrostratin C (**4**), as well as a pair of new enantiomeric diketopiperazines, (±)-5-hydroxydiphenylalazine A (**5**), along with five known analogues (**6**–**10**), were isolated and identified from the culture extract of *Epicoccum nigrum* SD-388, a fungus obtained from deep-sea sediments (−4500 m). Their structures were established on the basis of detailed interpretation of the NMR spectroscopic and mass spectrometric data. X-ray crystallographic analysis confirmed the structures and established the absolute configurations of compounds **1**–**3**, while the absolute configurations for compounds **4** and **5** were determined by ECD calculations. Compounds **4** and **10** showed potent activity against Huh7.5 liver tumor cells, which were comparable to that of the positive control, sorafenib, and the disulfide bridge at C-2/C-2' is likely essential for the activity.

**Keywords:** *Epicoccum nigrum*; deep-sea-derived fungus; thiodiketopiperazines; diketopiperazine enantiomers; cytotocxic activity
