Bioactive Secondary Metabolites of Two Chinese Edible Boletes, Phlebopus portentosus and Butyriboletus roseoflavus

This study investigated the phytochemical profiles and bioactivities of two edible boletes from Southwestern China, <i>Phlebopus portentosus</i> and <i>Butyriboletus roseoflavus</i>. A total of 33 secondary metabolites, comprising 15 alkaloids, 4 pulvinic acid derivative pigments, and 14 ergosterols, were isolated and identified. To our best knowledge, boletesine A (<b>1</b>), boletesine B (<b>2</b>), and <i>cis</i>-xerocomic acid (<b>16</b>) were previously undescribed compounds. The new structures were established by extensive spectroscopic methods and chemical calculations. Compound <b>1</b> features a hitherto unknown hybrid skeleton formed between a 2-formylpyrrole-alkaloid and a dopacetic acid (DOPAC) via a Michael addition reaction. Bioactivity assays revealed the neuroprotective effects of compounds <b>18</b> and <b>19</b> against Aβ_25-35- or H₂O₂-induced toxicity. In a cytotoxic assay against a small panel of cancer cell lines, compound <b>9</b> exhibited significant activity against HeLa cells (IC₅₀ = 10.76 µM), while <b>33</b> demonstrated broad-spectrum cytotoxicity against Hela229, SGC7901, PC-3, and BEL7402 cells (IC_50s in the range of 20~30 µM). Of particular note is the anti-influenza virus activities against A/H3N2 and B/Victoria strains of compounds <b>22</b> and <b>26</b> (EC₅₀ values ranging from 3.6 to 9.6 µM). Along with these, compound <b>29</b> showed a moderate antiviral effect against coxsackievirus B3. These findings underscore the therapeutic potential of the two edible boletes in addressing neurodegenerative diseases, cancer, and viral infections, paving the way for their prospective applications in the development of functional foods and pharmaceuticals.