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.Podostroma cornu-damae is a lethal toxic mushroom belonging to the Hypocreaceae family and contains fatal trichothecenes, a large family of chemically related mycotoxins that present a potential threat to public health throughout the world. 1 The mushroom, which is widely distributed in Japan, China, and East Asia, is known as the red deer's horn mushroom due to its exceptional deer-horn-like appearance. 2 Because the shape of P. cornu-damae resembles immature Ganoderma lucidum and Cordyceps medicinal mushrooms, fatal poisonings have occurred accidentally from misunderstandings involving these mushrooms. 2,3 In Japan, 13 cases of accidental intoxication of P. cornu-damae were reported from 1983 to 2008, including two deaths after ingesting only a few centimeters of its fruiting body. 2,3 In Korea, of two people who ate boiled fungus, one person died because of multiorgan failure in spite of aggressive medical intervention, and the other improved after conservative management for one month. 1,4 The early symptoms of poisoning are vomiting, dehydration, and diarrhea. After approximately 3 days, anuria, hypotension, polypnea, leukopenia, thrombocytopenia, and disturbance of consciousness have been reported. 2,3 There is only one report on the chemical investigation of toxic metabolites from P. cornu-damae, 5 where satratoxin H 12′,18′-diacetate, satratoxin H 12′-acetate, and satratoxin H 13′-acetate have been identified as new macrocyclic trichothecenes. All of the isolated macrocyclic
