Lanostane Triterpenes from the Tibetan Medicinal Mushroom <i>Ganoderma leucocontextum</i> and Their Inhibitory Effects on HMG-CoA Reductase and α‑Glucosidase

Sixteen new lanostane triterpenes, ganoleucoins A–P (<b>1</b>–<b>16</b>), together with 10 known tripterpenes (<b>17</b>–<b>26</b>), were isolated from the cultivated fruiting bodies of <i>Ganoderma leucocontextum</i>, a new member of the <i>Ganoderma lucidum</i> complex. The structures of the new compounds were elucidated by extensive spectroscopic analysis and chemical transformation. The inhibitory effects of <b>1</b>–<b>26</b> on HMG-CoA reductase and α-glucosidase were tested <i>in vitro</i>. Compounds <b>1</b>, <b>3</b>, <b>6</b>, <b>10</b>–<b>14</b>, <b>17</b>, <b>18</b>, <b>23</b>, <b>25</b>, and <b>26</b> showed much stronger inhibitory activity against HMG-CoA reductase than the positive control atorvastatin. Compounds <b>13</b>, <b>14</b>, and <b>16</b> presented potent inhibitory activity against α-glucosidase from yeast with IC₅₀ values of 13.6, 2.5, and 5.9 μM, respectively. In addition, the cytotoxicity of <b>1</b>–<b>26</b> was evaluated against the K562 and PC-3 cell lines by the MTT assay. Compounds <b>1</b>, <b>2</b>, <b>6</b>, <b>7</b>, <b>10</b>, <b>12</b>, <b>16</b>, <b>18</b>, and <b>25</b> exhibited cytotoxicity against K562 cells with IC₅₀ values in the range 10–20 μM. Paclitaxel was used as the positive control with an IC₅₀ value of 0.9 μM. This is the first report of secondary metabolites from this medicinal mushroom