title: Inhibitory Effects of Highly Oxygenated Lanostane Derivatives from the Fungus Ganoderma lucidum on P-Glycoprotein and α-Glucosidase.
abstract: 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 (1-5 and 8), lanostane nor-triterpenoids with 25 carbons (6 and 7), and lanostane triterpenoids (9-12) based on multiple spectroscopic data analysis, including HRESIMS, 1D-NMR, 2D-NMR, and CD. Compounds 1-5 were identified as rare nor-lanostanoids that contain a 17β-pentatomic lactone ring. Compound 13, possessing a lactone ring, had been isolated previously. The P-glycoprotein (P-gp) inhibitory effects of compounds 1-21 were evaluated at a concentration of 20 μM 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 α-glucosidase compared with those of the positive control acarbose.
authors.forename: Xi-Run
authors.initials: XR
authors.lastname: Zhao
authors.forename: Xiao-Kui
authors.initials: XK
authors.lastname: Huo
authors.affiliation: Laboratory of Pharmaceutical Resource Discovery, Dalian Institute of Chemical Physics, Chinese Academy of Sciences , Dalian 116023, People's Republic of China.
authors.forename: Pei-Pei
authors.initials: PP
authors.lastname: Dong
authors.forename: Chao
authors.initials: C
authors.lastname: Wang
authors.forename: Shan-Shan
authors.initials: SS
authors.lastname: Huang
authors.forename: Bao-Jing
authors.initials: BJ
authors.lastname: Zhang
authors.forename: Hou-Li
authors.initials: HL
authors.lastname: Zhang
authors.forename: Sa
authors.initials: S
authors.lastname: Deng
authors.forename: Ke-Xin
authors.initials: KX
authors.lastname: Liu
authors.forename: Xiao-Chi
authors.initials: XC
authors.lastname: Ma
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000378:metabolism*; D004317:Doxorubicin / Q000494:pharmacology; D005260:Female; D048690:Fruiting Bodies, Fungal / Q000737:chemistry; D065089:Glycoside Hydrolase Inhibitors / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D006801:Humans; D007810:Lanosterol / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D020940:Reishi / Q000737:chemistry*; D000520:alpha-Glucosidases / Q000187:drug effects*
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D065089:Glycoside Hydrolase Inhibitors; D007810:Lanosterol; D004317:Doxorubicin; D000520:alpha-Glucosidases