Selective cholinesterase inhibition by lanostane triterpenes from fruiting bodies of Ganoderma lucidum

Two new lanostane triterpenes, named methyl ganoderate A acetonide (1) and n-butyl ganoderate H (2), were isolated from the fruiting bodies of Ganoderma lucidum together with 16 known compounds (3–18). Extensive spectroscopic and chemical studies established the structures of these compounds as methyl 7β,15α-isopropylidenedioxy-3,11,23-trioxo-5α-lanost-8-en-26-oate (1) and n-butyl 12β-acetoxy-3β-hydroxy-7,11,15,23-tetraoxo-5α-lanost-8-en-26-oate (2). Because new compounds exhibiting specific anti-acetylcholinesterase activity are being sought as possible drug candidates for the treatment of Alzheimer’s and related neurodegenerative diseases, compounds 1–18 were examined for their inhibitory activities against acetylcholinesterase and butyrylcholinesterase. All of the compounds exhibited moderate acetylcholinesterase-inhibitory activity, with IC50 values ranging from 9.40 to 31.03 μM. In contrast, none of the compounds except lucidadiol (13) and lucidenic acid N (14) exhibited butyrylcholinesterase-inhibitory activity at concentrations up to 200 μM. These results indicate that these lanostane triterpenes are preferential inhibitors of acetylcholinesterase and may be suitable drug candidates.

Graphical abstractTwo new lanostane triterpenes, named methyl ganoderate A acetonide (1) and n-butyl ganoderate H (2), were isolated from the fruiting bodies of Ganoderma lucidum together with 16 known compounds (3–18). The inhibitory effects of the isolated compounds 1–18 on AChE and BChE in vitro were examined.Figure optionsDownload full-size imageDownload as PowerPoint slide