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

• Published in: Journal of natural products (Washington, D.C.) Vol. 78; no. 8; pp. 1977 - 1989
• Main Authors: Wang, Kai, Bao, Li, Xiong, Weiping, Ma, Ke, Han, Junjie, Wang, Wenzhao, Yin, Wenbing, Liu, Hongwei
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society and American Society of Pharmacognosy 28.08.2015; Amer Chemical Soc
• Subjects: Acyl Coenzyme A - drug effects; Agaricales - chemistry; alpha-glucosidase; alpha-Glucosidases - drug effects; Chemistry, Medicinal; cytotoxicity; fruiting bodies; Fruiting Bodies, Fungal - chemistry; Ganoderma; Ganoderma - chemistry; Ganoderma lucidum; Glycoside Hydrolase Inhibitors - chemistry; Glycoside Hydrolase Inhibitors - isolation & purification; Glycoside Hydrolase Inhibitors - pharmacology; Humans; Hydroxymethylglutaryl CoA Reductases - drug effects; hydroxymethylglutaryl-CoA reductases; Hydroxymethylglutaryl-CoA-Reductases, NADP-dependent - drug effects; Inhibitory Concentration 50; K562 Cells; Life Sciences & Biomedicine; medicinal fungi; Molecular Structure; paclitaxel; Paclitaxel - pharmacology; Pharmacology & Pharmacy; Plant Sciences; Science & Technology; secondary metabolites; spectral analysis; Tibet; Triterpenes - chemistry; Triterpenes - isolation & purification; Triterpenes - pharmacology; triterpenoids; yeasts; Tibet; CANCER-CELLS; GLYCOSIDES; APOPTOSIS; SINENSE; ACID; METAANALYSIS; CORDYCEPS; LUCIDUM; CYTOTOXICITY; CONSTITUENTS
• ISSN: 0163-3864; 1520-6025; 1520-6025
• DOI: 10.1021/acs.jnatprod.5b00331

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.