# Terpenes as Potential Anti-Alzheimer's Disease Agents
## 2 Activities of Terpenes on the Mechanisms Associated with AD
### Inhibition of Acetylcholinesterase (AChE)
#### 2.4.4. Triterpenenes
Considering now the compounds that have double bonds on the side chain linked to C17 but are not conjugated with the carboxylic group, like ganoderenic acid D (**164**), ganoderenic acid H (**165**), ganoderenic acid K (**166**), 3\(\beta\),7\(\beta\)-dihydroxy-11,15,23-trioxo-lanost-8,16-dien-26-oic acid (**167**), ganoderic acid E (**168**), 12-acetoxy-3,7,11,15,23-pentaoxolanost-8,20 dien-26-oic acid (**169**), 7/8-hydroxy-3,11,15,23-tetraoxo-27\(\xi\)-lanost-8,16-dien-26-oic acid (**170**), gandoregenic acid B (**171**), gandorencic acid F (**172**), gandorenoid D (**173**), gandorenoid F (**174**), gandorenic acid C (**175**), and 3\(\beta\)-hydroxyganodernoid D (**176**), they inhibit AChE with IC\({}_{50}\) > 200 uM, suggesting the significance for the inhibition of AChE of the conjugated double bonds on the side chain linked to C17 between C24 and C25 and the carboxylic group. Considering now gandoric acid H (**177**), 12\(\beta\)-hydroxyganoderenic acid F (**178**), methylganoderate F (**179**), gandorcic acid J (**180**), gandoric acid F (**181**), and gandoric acid AP (**182**), all of them are inactive (IC\({}_{50}\) > 200 uM) as they have no double bond between carbons on the side chain linked to C17, and rings B and C have a conjugated system between them comprising C7, C8, C9, and C11 and a carbonyl group at C15. Even compounds having no long conjugated system comprising C7, C8, C9, and C11, but having no double bond between C24 and C25, as is the case for ganducidic acid E (**160**) and 11\(\beta\)-hydroxy-3,7-diox-5\(\alpha\)-lanosta-8,24(E)-dien-26-oic acid (**161**), like gandoric acid B (**183**), C (**184**), D (**185**), G (**186**), and N (**187**) and methyl gandorate G (**188**), are inactive against AChE (IC\({}_{50}\) > 200 uM). Besides ganducidic acid E (**160**) and 11\(\beta\)-hydroxy-3,7-diox-5\(\alpha\)-lanosta-8,24(E)-dien-26-oic acid (**161**), ten other compounds inhibit AChE with IC\({}_{50}\) < 200 uM. These compounds were identified as gandoric acid Am1 (**189**), methyl gandorate C (**190**), gandorenoid C (**191**), 12\(\beta\)-hydroxyganodernic acid F (**192**), methyl gandorate E (**193**), gandoric acid C6 (**194**), methyl gandor acidic C6 (**195**), gandorenoid A (**196**), gandorenicid B2 (**197**), and ganderlactone G (**198**) with IC\({}_{50}\) values for the inhibition of AChE of 183.0, 148.0, 142.0, 102.0, 45.8, 147.5, 145.2, 149.0, 102.4, and 130.5 uM, respectively. All of them are weak inhibitors of AChE. Compared with the significant inhibitory effects presented by ganducidic acid E (**160**) and 11\(\beta\)-hydroxy-3,7-diox-5\(\alpha\)-lanosta-8,24(E)-dien-26-oic acid (**161**), it can be concluded that the C17 side chain may serve as the key feature for AChE inhibition, especially when it contains the conjugated double bonds on the side chain linked to C17 between C24 and C25 and the carboxylic group. Four other compounds, with a different side chain linked to C17, were identified as lucidone A (**199**), lucidone D (**200**), gandorenzoid B (**201**), and gandorenzanondiol (**202**). All of them were inactive against AChE (IC\({}_{50}\) > 200 uM). These results suggest, again, the significance of the side chain linked to C17. Overall, among the lanostane-type triterpenes extracted from the fruiting bodies of _G. lucidum_, the major components have 30 carbons (known as gandoric acids), but many of them have 27, 25, or 24 carbons. The results indicate that the C30 gandoric acids are the main active components for the inhibition of AChE. The structure of the side chain linked to C17 has an important effect on the inhibition of AChE. Indeed, the length of the side chain affects the activity of the lanostane-type triterpenes being ideal, with eight carbons and with a double bond between C24 and C25 and a carboxylic group at C25 [114; 132].