Isolation and target identification of antihepatoma polyprenylphenols from the edible mushroom Suillus granulatus.

Eight polyprenylphenol derivatives were isolated from the wild edible mushroom Suillus granulatus, including seven novel compounds, named suillin F-L (2-8), and one previously identified compound (1). The structures of the new compounds were elucidated using HR-ESI-MS and 1D and 2D NMR data. The absolute configuration of compound 8 was assigned based on the comparison of the experimental and calculated ECD data. All isolated compounds were evaluated for their cytotoxicity against HepG2 cancer cell lines. Compounds 1 and 3-6 demonstrated significant antitumor activity compared to the positive control (cisplatin), with IC50 values ranging from 8.19 to 13.97 µM. Furthermore, DARTS assay and LC-MS/MS analysis were used to identify HSP90AA1 as the direct target of compound 5, and the interaction between compound 5 and HSP90AA1 was verified by molecular docking.

Six new polyphenolic metabolites isolated from the Suillus granulatus and their cytotoxicity against HepG2 cells.

Edible mushrooms are an important source of nutraceuticals and for the discovery of bioactive metabolites as pharmaceuticals. In this work, six new polyphenolic metabolites suillusol A-D (1-4), suillusinoic acid (5), ethyl suillusinoate (6), were isolated from the Suillus granulatus. The structures of new compounds were elucidated using high-resolution electrospray ionization mass spectroscopy, nuclear magnetic resonance data, and single-crystal X-ray diffraction analysis. As far as we know, compound 1 represents an unprecedented type of natural product and compound 3 represents a new type of polyphenol fungal pigment, which may be biosynthetically related to thelephoric acid. The cytotoxicity against HepG2 cells of the new compounds were also evaluated. Compound 2 demonstrate significant inhibitory activity against HepG2 cells with IC50 values of 10.85 µM, surpassing that of positive control cisplatin. Moreover, compound 1 and 3 also exhibited moderate cytotoxic activity with their IC50 values measured at 35.60 and 32.62 µM, respectively. Our results indicate that S. granulatus is a rich source of chemical constituents that may provide new lead compounds for the development of anticancer agents.