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

Abstract 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 α-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 α-glucosidase from both yeast and rat small intestinal mucosa. Ganomycin I ( 4 ), the most potent inhibitor against both α -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.