Lanostane Triterpenes from the Tibetan Medicinal Mushroom Ganoderma leucocontextum and Their Inhibitory Effects on HMG-CoA Reductase and α-Glucosidase.
Sixteen new lanostane triterpenes, ganoleucoins A-P (1-16), together with 10 known tripterpenes (17-26), were isolated from the cultivated fruiting bodies of Ganoderma leucocontextum, a new member of the Ganoderma lucidum complex. The structures of the new compounds were elucidated by extensive spectroscopic analysis and chemical transformation. The inhibitory effects of 1-26 on HMG-CoA reductase and α-glucosidase were tested in vitro. Compounds 1, 3, 6, 10-14, 17, 18, 23, 25, and 26 showed much stronger inhibitory activity against HMG-CoA reductase than the positive control atorvastatin. Compounds 13, 14, and 16 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 1-26 was evaluated against the K562 and PC-3 cell lines by the MTT assay. Compounds 1, 2, 6, 7, 10, 12, 16, 18, and 25 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.
State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences , No. 1 Beichenxi Road, Chaoyang District, Beijing 100101, People's Republic of China.|University of Chinese Academy of Sciences , Beijing 100049, People's Republic of China.
Kai
K
Wang
State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences , No. 1 Beichenxi Road, Chaoyang District, Beijing 100101, People's Republic of China.
Li
L
Bao
Institute of Vegetable Research, Tibet Academy of Agriculture and Animal Science , No. 157 Jinzhuxi Road, Lasa 850000, People's Republic of China.
Weiping
W
Xiong
State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences , No. 1 Beichenxi Road, Chaoyang District, Beijing 100101, People's Republic of China.
Ke
K
Ma
State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences , No. 1 Beichenxi Road, Chaoyang District, Beijing 100101, People's Republic of China.
Junjie
J
Han
State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences , No. 1 Beichenxi Road, Chaoyang District, Beijing 100101, People's Republic of China.
Wenzhao
W
Wang
State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences , No. 1 Beichenxi Road, Chaoyang District, Beijing 100101, People's Republic of China.
Wenbing
W
Yin
State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences , No. 1 Beichenxi Road, Chaoyang District, Beijing 100101, People's Republic of China.
Hongwei
H
Liu
D000214:Acyl Coenzyme A / Q000187:drug effects; D000363:Agaricales / Q000737:chemistry*; D048690:Fruiting Bodies, Fungal / Q000737:chemistry; D032902:Ganoderma / Q000737:chemistry*; D065089:Glycoside Hydrolase Inhibitors / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000187:drug effects; D025782:Hydroxymethylglutaryl-CoA-Reductases, NADP-dependent / Q000187:drug effects*; D020128:Inhibitory Concentration 50; D020014:K562 Cells; D015394:Molecular Structure; D017239:Paclitaxel / Q000494:pharmacology; D018609:Tibet; D014315:Triterpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D000520:alpha-Glucosidases / Q000187:drug effects
D000214:Acyl Coenzyme A; D065089:Glycoside Hydrolase Inhibitors; D014315:Triterpenes; C008047:3-hydroxy-3-methylglutaryl-coenzyme A; D006903:Hydroxymethylglutaryl CoA Reductases; D025782:Hydroxymethylglutaryl-CoA-Reductases, NADP-dependent; D000520:alpha-Glucosidases; D017239:Paclitaxel