Heterodimeric diketopiperazine alkaloids from Penicillium expansum MA147 and their cytotoxicity†

Four previously undescribed heterodimeric diketopiperazine alkaloids, expansines A–D, were identified from the solid rice medium fermented by Penicillium expansum MA147, along with one new resorcylic acid derivative and five known compounds. Their structures and relative/absolute configurations were elucidated by interpretation of their spectroscopic data, quantum chemical calculations, and chemical conversion. Some obtained compounds were evaluated for the cytotoxicity against a triple-negative breast cancer cell line MDA-MB-231, and expansine C showed an IC₅₀ value of 3.23 μM. In further mechanistic studies, we found that it might act by increasing the expression of ATP-binding cassette transporter A1 and reducing cellular cholesterol levels, suggesting its potential as a novel anti-cancer agent.