Tersaphilones A-E, cytotoxic chlorinated azaphilones from the deep-sea-derived fungus Phomopsis tersa FS441

Abstract Five new chlorinated azaphilone derivatives, tersaphilones A-E along with three known analogues were isolated from the deep-sea-derived fungus Phomopsis tersa FS441. Structures of the new compounds with absolute configurations were determined by comprehensive chemical analyses including spectroscopic techniques, ECD calculation, and single crystal X-ray diffraction. Among them, tersaphilone B possessed the unique 6/6-6 carbon skeleton with a cleaved tetrahydrofuranyl ring. Besides, tersaphilones D and E were a pair of diastereomers featuring a characteristic epoxide ring, which were rarely-occurring in azaphilones. Moreover, all compounds were evaluated for their anticancer activity using a panel of four tumor cell lines, wherein the novel tersaphilones D and E showed significant cytotoxicity against MCF-7, SF-268, and A549 cell lines with the IC50 values ranging from 5.4 to 8.3 μM.