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

• Published in: Química Nova 2017-09, Vol.40 (9), p.1045-1050
• Main Authors: dos Santos, Gabriel Franco, Pereira, Rondinelle Gomes, Boaventura, Maria Amélia Diamantino, Macias, Francisco A, Lima, Gesiane da Silva, Coelho, Amanda Cristina Soares, Molinillo, José María González, Cala, Antonio, Takahashi, Jacqueline A.
• Format: Article
• Language: English
• Subjects: acetylcholinesterase inhibitors; Alzheimer's disease; kaurane diterpenes
• ISSN: 0100-4042; 1678-7064; 1678-7064
• DOI: 10.21577/0100-4042.20170112

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.