Cytotoxic Thiodiketopiperazine Derivatives from the Deep Sea-Derived Fungus SD-388.

Four new thiodiketopiperazine alkaloids, namely, 5'-hydroxy-6'-ene-epicoccin G (), 7-methoxy-7'-hydroxyepicoccin G (), 8'-acetoxyepicoccin D (), and 7'-demethoxyrostratin C (), as well as a pair of new enantiomeric diketopiperazines, (±)-5-hydroxydiphenylalazine A (), along with five known analogues (-), were isolated and identified from the culture extract of 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 -, while the absolute configurations for compounds and were determined by ECD calculations. Compounds and 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.