Macrocyclic trichothecenes from Myrothecium verrucaria PA 57 and their cytotoxic activity

Four undescribed macrocyclic trichothecenes, mytoxins D–G (1–4), together with four known related compounds (5–8) were isolated from the ethyl acetate extract of fermented rice of the fungus Myrothecium verrucaria PA57. All of them share a tricyclic 12,13-epoxytrichothec-9-ene (EPT) core and mytoxin G (4) represents the first example of a macrocyclic trichothecene with a glucosyl unit in the trichothecene moiety. The structures of the undescribed compounds were determined by a combination of extensive spectroscopic data analysis and quantum chemical calculations. All isolates demonstrated cytotoxic effects against CAL27 and HCT116 cell lines, which representing human oral squamous cell carcinoma and colorectal cancer, respectively. Mytoxin D (1) and mytoxin F (3) exhibited significant cytotoxicity against both cancer cell lines, with IC₅₀ values ranging from 3 to 6 nM. Additionally, compounds 1 and 3 induced apoptosis in HCT116 cells through activating caspase-3.