N-Hydroxy-Phe-Phe, a new dipeptide, and cytotoxic macrocyclic trichothecenes from the lethal toxic mushroom Podostroma cornu-damae

Abstract

Podostroma cornu-damae, commonly referred to as the red deer's horn mushroom due to its distinct resemblance to the antlers of a deer, is a lethal toxic mushroom that causes vomiting, dehydration, diarrhea, disturbance of consciousness, and even death. In continuation of our research aiming to investigate the novel structural and/or biological principles present in Korean wild mushrooms, a new N-hydroxyphenylalanine-phenylalanine dipeptide, N-hydroxy-Phe-Phe (1), and three known macrocyclic trichothecenes, satratoxin H (2), 12′-episatratoxin H (3), and roridin F (4), were isolated from the MeOH extract of a plate culture of the poisonous mushroom P. cornu-damae. The chemical structure of the new dipeptide (1) was determined by analyzing 1D and 2D NMR spectra and high-resolution (HR)-electrospray ionization mass spectroscopy (ESIMS), along with a computational method combined with a statistical procedure (DP4+), and its absolute configuration was unambiguously assigned by quantum chemical ECD calculations. To the best of our knowledge, compound 1 is the first dipeptide found in P. cornu-damae. Upon evaluating the cytotoxicity of compounds 1–4 against four human-derived cancer cell lines namely SK-OV-3, SK-MEL-2, A549, and HCT15, 12′-episatratoxin H (3) displayed potent cytotoxic effects toward all four cell lines tested, with IC₅₀ values ranging from 0.7 to 2.8 nM, which was found to be stronger than that of doxorubicin. Satratoxin H (2) also demonstrated moderate cytotoxic potency against all four cell lines, with IC₅₀ values ranging from 1.93 to 4.22 μM. Our findings provide experimental data supporting the potential of the poisonous mushroom P. cornu-damae as a source of anticancer agents.