Lee_2011_Bioorg.Med.Chem.Lett_21_6603

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 7beta,15alpha-isopropylidenedioxy-3,11,23-trioxo-5alpha-lanost-8-en-26-oate (1) and n-butyl 12beta-acetoxy-3beta-hydroxy-7,11,15,23-tetraoxo-5alpha-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 IC(50) values ranging from 9.40 to 31.03muM. In contrast, none of the compounds except lucidadiol (13) and lucidenic acid N (14) exhibited butyrylcholinesterase-inhibitory activity at concentrations up to 200muM. These results indicate that these lanostane triterpenes are preferential inhibitors of acetylcholinesterase and may be suitable drug candidates.