Inhibitory Effects of Highly Oxygenated Lanostane Derivatives from the Fungus Ganoderma lucidum on P-Glycoprotein and 伪-Glucosidase

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• 作者：Xi-Run Zhao ; Xiao-Kui Huo ; Pei-Pei Dong ; Chao Wang ; Shan-Shan Huang ; Bao-Jing Zhang ; Hou-Li Zhang ; Sa Deng ; Ke-Xin Liu ; Xiao-Chi Ma
• 刊名：Journal of Natural Products
• 出版年：2015
• 出版时间：August 28, 2015
• 年：2015
• 卷：78
• 期：8
• 页码：1868-1876
• 全文大小：422K
• ISSN：1520-6025

文摘

Twelve new highly oxygenated lanostane triterpenoids and nine known ganoderic acids were isolated from the fruiting body of Ganoderma lucidum. The new compounds were lanostane nortriterpenoids with 27 carbons (1鈥?b>5 and 8), lanostane nor-triterpenoids with 25 carbons (6 and 7), and lanostane triterpenoids (9鈥?b>12) based on multiple spectroscopic data analysis, including HRESIMS, 1D-NMR, 2D-NMR, and CD. Compounds 1鈥?b>5 were identified as rare nor-lanostanoids that contain a 17尾-pentatomic lactone ring. Compound 13, possessing a lactone ring, had been isolated previously. The P-glycoprotein (P-gp) inhibitory effects of compounds 1鈥?b>21 were evaluated at a concentration of 20 渭M using an adriamycin (ADM)-resistant human breast adenocarcinoma cell line (MCF-7/ADR). Compounds 1, 5, 18, and 20 and verapamil increased the accumulation of ADM in MCF-7/ADR cells approximately 3-fold when compared with the negative control. These data support the significant P-glycoprotein inhibitory activities of compounds 1, 5, 18, and 20. In silico docking analysis suggested these compounds had similar P-gp recognition mechanisms compared with those of verapamil (a classical inhibitor). Furthermore, in an in vitro bioassay, compounds 2, 4, 5, 6, and 18 showed moderate inhibitory effects against 伪-glucosidase compared with those of the positive control acarbose.