Discovery of Aflatoxins and Sterigmatocystins with Antitumor Activity from Aspergillus sp. PQJ-1 of Sphagneticola trilobata.

Fourteen mycotoxins (1-14) were isolated and identified from a Sphagneticola trilobata-derived fungus, Aspergillus sp. PQJ-1, including two new aflatoxins, asperaflatoxins C (3) and D (4), one new sterigmatocystin, Q (7), and 11 known analogues (1, 2, 5, 6, 8-14). Among them, three pairs are epimers (1 and 2, 11 and 12, 13 and 14). Their structures and absolute configurations were determined by NMR, HRESIMS, X-ray diffraction analyses, and ECD calculation. 1 and 2 were isolated as new natural products, with their 13C NMR spectral data reported for the first time. Notably, 4 represents the first compound featuring a unique five-membered lactone carbon skeleton. 1 demonstrated the most cytotoxic effects on HeLa cells with an IC50 value of 5.43 μM. Network pharmacological screening results showed that the mechanism of 1 may be closely related to cell migration and apoptosis. Molecular docking showed that 1 could effectively bind to key target Bcl-2, MMP9, PIK3CA, and EGFR. And the Western blotting experiment confirmed that 1 could down-regulate key proteins such as Bcl-2, MMP9, and EGFR at the protein level. In addition, 1 could up-regulate BAX and down-regulate Bcl-2 and Caspase-3 in mRNA expression based on the qRT-PCR assay. In vivo experiments were also performed for 1.