MURRAY Ana paula
congresos y reuniones científicas
Lupane triterpenoids, selective butyrylcholinesterase inhibitors
MARIA JULIA CASTRO; ANA PAULA MURRAY; FARAONI, MARÍA BELEN
Conferencia; 18 th International Electronic Conference on Synthetic Organic Chemistry.; 2014
Alzheimer´s disease (AD) is a progressive neurodegenerative disorder associated with memory impairment and cognitive deficit. It is characterized by low levels of the neurotransmitter acetylcholine (ACh) in the brain of AD patients. The inhibition of acetylcholinesterase (AChE), the enzyme that catalyzes ACh hydrolysis, is the main therapeutic strategy used to treat AD. In the healthy brain, another enzyme, namely butyrylcholinesterase (BChE), is involved in the metabolic degradation of ACh. BChE activity increases as AD progresses, which suggests that BChE may play an important role at the latter stages of AD. Therefore, selective BChE inhibitors attract interest nowadays. The chemistry of lupane-type triterpenoids has been actively explored due to their biological and pharmacological properties. Abundant in many plants, these metabolites are valuable natural raw materials to perform chemical modifications. In the present work, we aimed to evaluate natural and semisynthetic lupanes as potential in vitro cholinesterase inhibitors. Lupeol (1) (lup-20(29)-en-3B-ol) and calenduladiol (2) (lup-20(29)-en-3B,16B-diol) have been isolated from Chuquiraga erinacea subsp. erinacea (Asteraceae), an endemic species growing wildly in our region. Semisynthetic lupanes 3-17 have been prepared from them. All of them failed to inhibit AChE, but we found that most of calenduladiol derivatives exhibited BChE inhibition. The best BChE inhibitors were 3B-hydroxylup-20(29)-en-16-one (5) and 3,16-dioxolup-20(29)-en-30-al (15) with IC50 values of 28.9 and 21.5 µM, respectively, an interesting result considering that the role of BChE is more relevant as the disease progresses.