Macrocyclic trichothecenes from Myrothecium verrucaria PA 57 and their cytotoxic activity

Abstract

Four novel macrocyclic trichothecenes, termed mytoxins D−G (1−4), along with four known analogs (5−8), were isolated from the ethyl acetate extract of fermented rice inoculated with the fungus Myrothecium verrucaria PA57. Each compound features a tricyclic 12,13-epoxytrichothec-9-ene (EPT) core. Notably, mytoxin G (4) represents the first instance of a macrocyclic trichothecene incorporating a glucosyl unit within the trichothecene structure. The structures of the newly identified compounds were elucidated through comprehensive spectroscopic analysis combined with quantum chemical calculations. All isolated compounds demonstrated cytotoxic activity against the CAL27 and HCT116 cell lines, which are models for human oral squamous cell carcinoma and colorectal cancer, respectively. Specifically, mytoxin D (1) and mytoxin F (3) exhibited pronounced cytotoxic effects against both cancer cell lines, with IC₅₀ values ranging from 3 to 6 nmol·L⁻¹. Moreover, compounds 1 and 3 were found to induce apoptosis in HCT116 cells by activating caspase-3.

Keywords

Macrocyclic trichothecenes / Myrothecium verrucaria / Cytotoxicity / Secondary metabolite / Soil fungi

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Funding

National Natural Science Foundation of China(82173713)

Natural Science Foundation of Hunan Province(2021JJ41000)

Natural Science Foundation of Hunan Province(2021JJ40812)

Key Research and Development Program of Hunan Province(2022SK2031)

Project of Hunan Administration of Traditional Chinese Medicine(B2023059)

Postgraduate Scientific Research Innovation Project of Hunan Province(CX20230323)