Using computer-based models, researchers have identified a number of compounds that could alleviate the symptoms of Alzheimer's disease1.
Reduced activity of neurons that respond to neurotransmitter acetylcholine (ACh) is a well-known trait of Alzheimer's disease. Acetylcholinesterase (AChE) is a substrate-specific enzyme that degrades ACh in the nerve synapses. An optimum level of acetylcholine should be maintained in the brain for its proper function.
Drugs such as rivastigmine, donepezil and galantamine can be used to inhibit the activity of AChE and prevent the breakdown of ACh. The most common adverse effects of these drugs include nausea and vomiting. In search of better AChE inhibitors, the researchers virtually screened three different small-compound databases, including the National Cancer Institute, Specs and InterBioScreen.
The researchers narrowed their search to nine lead compounds. While studying the efficacy of these lead compounds, they mimicked how donepezil binds to two active sites of AChE.
Two potential lead compounds were identified by a technique called AChE inhibitory assay. Computations showed that these compounds should have good oral bioavailability, little or no toxicity and the ability to penetrate the blood–brain barrier — all of which are key factors for drugs associated with the central nervous system.
The authors of this work are from: Department of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research (NIPER), Punjab, India, Department of Biosciences, Åbo Akademi University, Artillerigatan, Turku, and Division of Pharmaceutical Biology, Faculty of Pharmacy, University of Helsinki, Finland.
