A novel class of alpha-glucosidase and HMG-CoA reductase inhibitors from Ganoderma leucocontextum and the anti-diabetic properties of ganomycin I in KK-A(y) mice

作者：Wang, Kai; Bao, Li; Ma, Ke; Zhang, Jinjin; Chen, Baosong; Han, Junjie; Ren, Jinwei; Luo, Huajun; Liu, Hongwei^*

来源：European Journal of Medicinal Chemistry, 2017, 127: 1035-1046.

DOI：10.1016/j.ejmech.2016.11.015

• Ganoderma leucocontextum
• Meroterpenes
• HMG-CoA reductase inhibition
• alpha-Glucosidase inhibition
• Anti-diabetic activities

Three new meroterpenoids, ganoleucin A-C (1-3), together with five known meroterpenoids (4-8), were isolated from the fruiting bodies of Ganoderma leucocontextum. The structures of the new compounds were elucidated by extensive spectroscopic analysis, circular dichroism (CD) spectroscopy, and chemical transformation. The inhibitory effects of 1-8 on HMG-CoA reductase and a-glucosidase were tested in vitro. Ganomycin I (4), 5, and 8 showed stronger inhibitory activity against HMG-CoA reductase than the positive control atorvastatin. Compounds 1, and 3-8 presented potent noncompetitive inhibitory activity against alpha-glucosidase from both yeast and rat small intestinal mucosa. Ganomycin 1(4), the most potent inhibitor against both a-glucosidase and HMG-CoA reductase, was synthesized and evaluated for its in vivo bioactivity. Pharmacological results showed that ganomycin I (4) exerted potent and efficacious hypoglycemic, hypolipidemic, and insulin-sensitizing effects in KK-A(y) mice.

• 出版日期2017-2-15
• 单位真菌学国家重点实验室; 中国科学院大学; 中国科学院微生物研究所; 三峡大学