Macrocyclic Trichothecene Mycotoxins from a Deadly Poisonous Mushroom, Podostroma cornu-damae

Three new macrocyclic trichothecenes ( 1 – 3 ) and five known related compounds ( 4 – 8 ) were isolated from the MeOH extract of a plate culture of the fungus Podostroma cornu-damae, a deadly poisonous mushroom. Miophytocen D ( 1 ) is a rearranged macrocyclic type D trichothecene, featuring a bicyclo-[6.5]dodecahydrocyclopenta[ b ]chromene scaffold, and the structures of new compounds ( 1 – 3 ) were delineated by the combination of 1D and 2D NMR spectroscopic experiments and HRESIMS, modified Mosher’s esterification, and quantum chemical ECD calculations. The isolated compounds ( 1 – 8 ) were evaluated for cytotoxicity against four human breast cancer cell lines (Bt549, HCC70, MDA-MB-231, and MDA-MB-468). Compounds 4, 6, and 8 exhibited significant cytotoxic effects against the breast cancer cell lines, with IC 50 values in the range of 0.02–80 nM, which is stronger than doxorubicin, the positive control, and a structure–activity relationship was suggested.