Structure-activity relationship study of diterpenes for treatment of Alzheimer’s disease

Abstract

Alzheimer's disease is an irreversible, degenerative and age-related disease which is growing more and more with the increase in life expectancy. Kaurane diterpenes are a class of natural products available in large amounts in nature and isolated from plants grown worldwide. In the present work¸ twenty-seven kaurane diterpenes of natural origin and some readily available derivatives were assayed for acetylcholinesterase inhibition and the structure-activity relationship was analyzed. The kaurenoic acid derivatives screened showed to be promising inhibitors of AChE, which could provide new leads for drugs to fight Alzheimer's disease symptoms. Among them, eleven compounds showed activities comparable or higher than the positive control galantamine. Existence of an allylic hydroxyl group showed to be an important structural feature for AChE inhibition. In addition, presence of free hydroxyl groups at C-17 and C-19, furnished a diol especially active, able to completely inhibit AChE.

Antimicrobial activity and acetilcolinesterase inhibition of oils and Amazon fruit extracts

“…On the other hand, there are compounds of natural origin that have the property of inhibiting acetylcholinesterase (AChE), a key enzyme in Alzheimer's disease. These compounds can be either isolated from plants or from microorganisms (dos Santos et al, 2017). Inhibition of AChE in vitro is attributed to several reasons, including the structure of phenolic compounds, considering the metabolism suffered by phenolic compounds after their ingestion at gastrointestinal tract and liver level (Roseiro et al, 2012).…”